ArticleLiterature Review

The Sulfur-Containing Amino Acids: An Overview

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Abstract

Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins. Sulfur belongs to the same group in the periodic table as oxygen but is much less electronegative. This difference accounts for some of the distinctive properties of the sulfur-containing amino acids. Methionine is the initiating amino acid in the synthesis of virtually all eukaryotic proteins; N-formylmethionine serves the same function in prokaryotes. Within proteins, many of the methionine residues are buried in the hydrophobic core, but some, which are exposed, are susceptible to oxidative damage. Cysteine, by virtue of its ability to form disulfide bonds, plays a crucial role in protein structure and in protein-folding pathways. Methionine metabolism begins with its activation to S-adenosylmethionine. This is a cofactor of extraordinary versatility, playing roles in methyl group transfer, 5'-deoxyadenosyl group transfer, polyamine synthesis, ethylene synthesis in plants, and many others. In animals, the great bulk of S-adenosylmethionine is used in methylation reactions. S-Adenosylhomocysteine, which is a product of these methyltransferases, gives rise to homocysteine. Homocysteine may be remethylated to methionine or converted to cysteine by the transsulfuration pathway. Methionine may also be metabolized by a transamination pathway. This pathway, which is significant only at high methionine concentrations, produces a number of toxic endproducts. Cysteine may be converted to such important products as glutathione and taurine. Taurine is present in many tissues at higher concentrations than any of the other amino acids. It is an essential nutrient for cats.

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... Taurine, unlike caffeine, behaves as an inhibitory neuromodulator. Its antioxidant and anti-inflammatory properties suggest its participation in several biological processes (the stabilization of the plasma membrane and bile salts, osmoregulation, calcium metabolism, skeletal muscle functionality and correct neuronal activity, among others) [46][47][48], but few studies have related dietary exposure with cardiovascular and neurological effects [49][50][51][52]. There are several dietary sources of taurine [36,46] that contribute to the estimated daily taurine intake (10-400 mg/day) [30] but, depending on the type of diet, the dietary intake may be lower (20-200 mg/day) [53]. ...
... Its antioxidant and anti-inflammatory properties suggest its participation in several biological processes (the stabilization of the plasma membrane and bile salts, osmoregulation, calcium metabolism, skeletal muscle functionality and correct neuronal activity, among others) [46][47][48], but few studies have related dietary exposure with cardiovascular and neurological effects [49][50][51][52]. There are several dietary sources of taurine [36,46] that contribute to the estimated daily taurine intake (10-400 mg/day) [30] but, depending on the type of diet, the dietary intake may be lower (20-200 mg/day) [53]. In the case of omnivorous diets, the daily intake is estimated to be at 58 mg of taurine/day [29]. ...
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Article
The consumption of energy drinks (EDs) is increasing globally while the evidence and concern about the potential health risks are also growing. Caffeine (generally 32 mg/100 mL) together with a wide variety of other active components such as taurine (usually 4000 mg/L) and D-glucuronolactone (generally 2400 mg/L) are the main ingredients of EDs. This study aims to assess the exposures to caffeine, taurine and D-glucuronolactone from EDs in various consumption scenarios and consumer profiles and to characterize the risks by evaluating caffeine and taurine intakes with their reference values and by calculating the margin of safety (MOS) for D-glucuronolactone. While the exposure assessment results showed that caffeine intakes from EDs ranged from 80 to 160 mg (1.14–4 mg/kg b.w.) for the considered scenarios, the risk characterization estimated some risks that could be managed with consumption recommendations such as limiting EDs in 40, 60 and 80 kg b.w. consumers to 175, 262.5 and 350 mL, respectively, to prevent sleep disturbances and to 375, 562.5 and 750 mL to prevent general caffeine adverse health risks, respectively. Dietary exposure to D-glucuronolactone from EDs ranged from 600 to 1200 mg (7.5–30 mg/kg b.w.). As D-glucuronolactone MOS ≥ 100 is only observed when EDs consumption is limited to 250 mL, for individuals weighing above 60 kg, some risks were observed in some of the studied scenarios. A taurine exposure from EDs varied from 1000 to 2000 mg (12.5–50 mg/kg b.w.) and consumptions over 500 mL were estimated to generate intakes above the reference value. In conclusion, the management of these risks requires a European legal framework for EDs with maximum limits for the active components, volume size limitations and labeling improvements along with the development of education and awareness programs and risk communication actions in collaboration with the industry and society.
... This situation is exacerbated in chickens as they have no sweat glands and are susceptible to thermal stress. Chickens under heat stress exhibit increased body temperatures, oxidative stress and metabolic amino acid alteration (Brosnan and Brosnan, 2006;Chowdhury et al., 2014;Oke O. E. et al., 2021;Chowdhury et al., 2021;Kpomasse et al., 2021). In addition to serving as protein building blocks, amino acids act as regulators of gene expression and mediators of phosphorylation of protein cascades. ...
... The plasma MDA and SOD of the birds treated with in ovo feeding of cysteine was better than the chicks of the control groups in the present study. When birds are under stress, the demand for Sulphur-containing amino acid-like cysteine increases since it is required to synthesise GSH in order to mitigate the damage caused by OS induced by HS (Brosnan, 2006;Bunchasak, 2009;Wu, 2009). The amino acids have a high antioxidant capability, keep free radicals in check and maintain a healthy equilibrium in the body (Bin et al., 2017). ...
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Article
The objective of this study was to evaluate the effect of in ovo feeding cysteine, lysine or their combinations on the perinatal and post-hatch physiological responses of broiler embryos exposed to heat stress during incubation. A total of two thousand fertile eggs of broiler breeders (Ross 308) flock (at 38 weeks of age) were used for this study. In the first 10 days, the eggs were incubated using the conventional protocol of relative humidity and temperature of 55% and 37.8°C respectively. From day ten onward, the temperature was increased to 39.6°C for 6 h per day. On day 17.5, 1,500 eggs with the evidence of living embryos were randomly selected and assigned to 6 treatments having five replicates of 50 eggs each. The treatments were: un-injected eggs (UI), eggs injected with only 0.5 ml distilled water (DW), 3.5 mg/egg cysteine (CY), 2mg/egg lysine (LY), 3.4 mg cysteine+2 mg lysine (CLH) and 1.7 mg cysteine+1 mg lysine (CLL). On day 21, the hatchability, anatomical characteristics, chick quality and the antioxidant status of the chicks were evaluated. During the post-hatch phase, data were collected on the haematology, biochemical parameters, growth performance and intestinal morphology of the birds. The results revealed that the hatchability of CY chicks was higher ( p < 0.05) than in the other treatments, while the lowest values were recorded in CLH. The hatching muscle of the chicks of CLL was similar to those of CY but higher ( p < 0.05) than the others. The MDA of DW and UI chickens was similar and higher than birds in the other treatment groups. The serum SOD of CLL birds was comparable to that of CY but higher than the values recorded in the other treatments. The final weights of CLL chickens were similar to those of LY but significantly higher ( p < 0.05) than those of the other treatments. The duodenal villus heights of the birds of CLL were higher than those of the other treatment groups, whereas the villus height of the birds of CLH was higher than those of UI, DW and CY. Overall, in ovo feeding of cysteine alone improved the hatchability of thermally-challenged broiler embryos. In contrast, a low-dose mixture of cysteine plus lysine improved the post-hatch growth performance.
... Sulfur (S) is one of the most important elements for life, and numerous biochemical processes are tightly linked to this element; for example, cysteine is essential in protein synthesis and in protein-folding pathways [1]. Organosulfur natural products (NPs) refer to the different kinds of natural products containing sulfur elements, such as thiols, thioesters, sulfoxides, etc. [2][3][4][5], which play an important role in the pharmaceutical industry. ...
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Article
Organosulfur natural products (NPs) refer to the different kinds of small molecular-containing sulfur (S) elements. Sulfur-containing NPs tightly link to the biochemical processes and play an important role in the pharmaceutical industry. The majority of S-containing NPs are generally isolated from Alliaceae plants or bacteria, and those from fungi are still relatively rare. In recent years, an increasing number of S-containing metabolites have been discovered in marine and terrestrial fungi, but there is no comprehensive and targeted review to summarize the studies. In order to make it more straightforward to better grasp the fungal-derived S-containing NPs and understand the particularity of marine S-containing NPs compared to those from terrestrial fungi, we summarized the chemical structures and biological activities of 89 new fungal-derived S-containing metabolites from 1929 when the penicillin was discovered to the present in this current review. The structural and bioactive diversity of these S-containing metabolites were concluded in detail, and the preliminary mechanism for C-S bond formation in fungi was also discussed briefly.
... For diagnostic testing of that pathology, the fluorescent dye could be used. In some cases, highly metabolic cells could be associated with sulfur-contained amino acids [2,3]. Changing in cysteine-contained peptide was found in tissues and organs in different pathology: from alcoholic liver disease [4] to neurological conditions, such as Huntington's disease [5]. ...
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Article
Linked to Alzheimer’s disease (AD), amyloids and tau-protein are known to contain a large number of cysteine (Cys) residues. In addition, certain levels of some common biogenic thiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH), etc.) in biological fluids are closely related to AD as well as other diseases. Therefore, probes with a selective interaction with the above-mentioned thiols can be used for the monitoring and visualizing changes of (bio)thiols in the biological fluids as well as in the brain of animal models of Alzheimer’s disease. In this study, new Eu(III), Tb(III), Gd(III) and Sm(III) complexes of 2,2′-bipyridine ligands containing TEMPO fragments as receptor units for (bio)thiols are reported. The presence of free radical fragments of the ligand in the complexes was proved by using the electronic paramagnetic resonance (EPR) method. Among all the complexes, the Eu(III) complex turned out to be the most promising one as luminescence- and spin-probe for the detection of biogenic thiols. The EPR and fluorescent titration methods showed the interaction of the resulting complex with free Cys and GSH in solution. To study the practical applicability of the probes for the monitoring of AD in-vivo, by using the above-mentioned Eu(III)-based probe, the staining of the brain of mice with amyloidosis and Vero cell cultures supplemented with the cysteine-enriched medium was studied as well as the fluorescence titration of Bovine Serum Albumin, BSA (as the model for the thiol moieties containing protein), was carried out. Based on the results of fluorescence titration, the formation of a non-covalent inclusion complex between the above-mentioned Eu(III) complex and BSA was suggested.
... Once inside plants, SO 4 2− is metabolized and assimilated into amino acids containing S in the form of sulfhydryl (-SH), such as methionine and cysteine, which can incorporate into proteins (Saggar et al., 1998;Brosnan and Brosnan, 2006). These amino acids are deprotonated, resulting in the release of H + into the rhizosphere. ...
Article
Soil acidification in managed ecosystems such as agricultural lands principally result from increased releasing of protons (H+) from the transformation reactions of carbon (C), nitrogen (N) and sulphur (S) containing compounds. The incorporation of liming materials can neutralize the protons released, hence reducing soil acidity and its adverse impacts to soil environment, food security, and human health. Biochar derived from organic residues are becoming a source of carbon input to soil and provide multifunctional values. Biochar can be alkaline in nature with the level of alkalinity dependent upon the feedstock and processing conditions. This review covers the fundamental aspects of soil acidification and of the use of biochar to address constraints related to acidic soil. Biochar are increasingly considered as an effective soil amendment for improving soil acidity owing to its liming potential, thereby enhancing soil fertility and productivity in acid soils. The ameliorant effect on acid soils is mainly because of the dissolution of carbonates, (hydro)-oxides of the ash fraction of biochar and potential use by microorganisms.
... Sulphur is present in a number of body metabolites (e.g., mucopolysaccharides) and if not adequately supplied in the diet, sulphur amino acids would likely be degraded. It was reported that sulphate must be present for choline to spare a maximum amount of methionine (12). The practical implication is that sulphate and choline need to be adequately provided in diets so that the more expensive and often marginally deficient nutrient methionine is not used to provide either of these nutrients. ...
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Article
An experiment was conducted to examine the sparing effect of choline and/or sulphate on methionine in serum biochemical indices of broiler chickens in a 21-days feeding trial. Two hundred (200) unsexed one-day old Arbor Acre broiler birds were randomly distributed into five dietary treatments consisting 5 replicates of 8 birds per replicate in a completely randomized design. Diet 1 was the control, a basal diet without any of the supplements (methionine, choline or sulphate, diet 2 had the basal diet with methionine (0.30%) only, diet 3 was the basal diet with 0.30% methionine + 0.10% choline, diet 4 was the basal diet with 0.10% choline+ 0.25% sulphate and diet 5 was the basal diet with 0.30% methionine+ 0.10%choline+ 0.25% sulphate. On day 21, two birds per replicate were bled at the jugular vein into heparin bottles for serum biochemical indices. Results showed that feed intake of birds fed methionine, methionine+choline and methionine+choline+sulphate supplemented diets were similar but significantly higher than those fed diets supplemented with choline+sulphate and the control diet. Similar trend was observed in the final body weight gain of birds on experimental diets. Improved feed conversion ratio was recorded for birds fed methionine, methionine+choline and methionine+choline+sulphate supplemented diets. Diets had significant (P<0.05) effect on glucose, blood urea nitrogen, creatinine, triglyceride, cholesterol, albumin and globulin but liver enzymes were not significant. Supplementation of methionine with the combination of choline and sulphate resulted in overall improvement of broiler biochemical parameters when compared with control and birds fed combination of choline and sulphate alone. Supplementing methionine with choline and sulphate also spares methionine in improving the health status of the broiler birds by regulating the serum lipids.
... Background Sulfur amino acids (SAAs) comprise the essential amino acid methionine and its derivatives [1,2]. Methionine is converted into homocysteine in the transmethylation pathway. ...
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Article
Purpose Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. Methods We examined cross-sectional subsets from the CODAM cohort (n = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC–MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. Results Methionine was associated with all measures of liver fat, e.g., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: β = 0.19 (0.09, 0.28); DMS: β = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: β = 0.15 (0.08, 0.23); DMS: β = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: β = 0.16 (0.08, 0.25); DMS: β = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. Conclusion Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.
... GSH is the cellular main antioxidant and is responsible for maintaining tissue homeostasis by regulating the redox state. 44 GSH depletion has been reported in the brain of patients with neurodegenerative diseases. That is why much of the research has focused on therapeutic strategies to develop drugs that increase GSH levels in the brain, since it is known that GSH direct administration has had little or null effects because this tripeptide hardly crosses the blood-brain barrier. ...
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Article
Neurodegenerative diseases have increased worldwide in recent years. Their relationship with oxidative stress has motivated the research to find therapies and medications capable of suppressing oxidative damage and therefore slowing the progression of these diseases. Glutathione (GSH) is the most important cellular antioxidant in living beings and is responsible for regulating the cellular redox state. However, GSH cannot be administered by any route of administration, so molecules that increase its levels by activating Nrf2-ARE signaling pathway are explored; since Nrf2 regulates the main genes involved in GSH de novo synthesis and recycling. Astrocytes are the most important cell-type in the antioxidant cell response and are responsible for providing GSH and other substrates for neurons to have an efficient antioxidant response. Methotrexate (MTX) is an anti-inflammatory agent that has different cellular effects when administered at low or high concentrations. So in this study, we used MTX different concentrations and exposure times to induce a hormetic antioxidant response in rat primary astrocytes. Our results showed that 20 nM MTX pre-conditioning for 12 h augmented the GSH/GSSG ratio and protected cellular viability against a toxic MTX and H 2 O 2 insult, which was abrogated when Nrf2 was inhibited by brusatol. Hence, MTX subsequent studies as a drug to counteract the progression of some stress-associated neurodegenerative diseases are suggested.
... Intracellular antioxidants glutathione and N-acetyl cysteine are produced by sulfur amino acids which are involved in the antioxidant defense mechanism (Colovic et al., 2018). Cysteine also forms a disulfide bond which plays a pivotal role in protein-folding pathways and protein structure (Brosnan and Brosnan, 2006). Sulfur increases the uptake of P (phosphorus) and N (nitrogen) during seed formation; moreover, it is an integral part of nucleic acid and protein synthesis (Shigi et al., 2021). ...
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Article
Nitrogen (N) is an important macro-nutrient required for crop production and is considered an important commodity for agricultural systems. Urea is a vital source of N that is used widely across the globe to meet crop N requirements. However, N applied in the form of urea is mostly lost in soil, posing serious economic and environmental issues. Therefore, different approaches such as the application of urea coated with different substances are used worldwide to reduce N losses. Urea coating is considered an imperative approach to enhance crop production and reduce the corresponding nitrogen losses along with its impact on the environment. In addition, given the serious food security challenges in meeting the current and future demands for food, the best agricultural management strategy to enhance food production have led to methods that involve coating urea with different nutrients such as sulfur (S) and zinc (Zn). Coated urea has a slow-release mechanism and remains in the soil for a longer period to meet the demand of crop plants and increases nitrogen use efficiency, growth, yield, and grain quality. These nutrient-coated urea reduce nitrogen losses (volatilization, leaching, and N 2 O) and save the environment from degradation. Sulfur and zinc-coated urea also reduce nutrient deficiencies and have synergetic effects with other macro and micronutrients in the crop. This study discusses the dynamics of sulfur and zinc-coated urea in soil, their impact on crop production, nitrogen use efficiency (NUE), the residual and toxic effects of coated urea, and the constraints of adopting coated fertilizers. Additionally, we also shed light on agronomic and molecular approaches to enhance NUE for better crop productivity to meet food security challenges.
... Methionine is an essential amino acid that can be considered the fundamental source of sulfur in cysteine biosynthesis. Indeed, cysteine is obtained from methionine through a transmethylation/trans-sulfuration pathway, which involves intermediates such as S-adenosylmethionine, S-adenosylhomocysteine, HCY and cystathionine, whose biological significance has been only partially elucidated [119]. Cysteine is the precursor of many fundamental biochemical factors, such as GSH, coenzyme A, taurine and H 2 S. Natural sulfur compounds derived from Alliaceae or Brassicaceae represent exogenous sources of H 2 S. Indeed, humans can convert organosulfur precursors (i.e., alliin and GLSs) to sulfur-containing molecules such as polysulfides and ITCs, which in turn release H 2 S through wellelucidated mechanisms [29,83] (see Fig. 1 and Fig. 2). ...
Article
Natural sulfur compounds are emerging as therapeutic options for the management of hypertension and prehypertension. They are mainly represented by polysulfides from Alliaceae (i.e., garlic) and isothiocyanates from Brassicaceae (or crucifers). The beneficial cardiovascular effects of these compounds, especially garlic polysulfides, are well known and widely reported both in preclinical and clinical studies. However, only a few authors have linked the ability of natural sulfur compounds to induce vasorelaxation and subsequent antihypertensive effects with their ability to release hydrogen sulfide (H2S) in biological tissue. H2S is an endogenous gasotransmitter involved in vascular tone regulation. Some cardiovascular diseases, such as hypertension, are associated with lower plasma H2S levels. Consequently, exogenous sources of H2S (H2S donors) have been designed and synthesized or identified among secondary plant metabolites as potential therapeutic options. In addition to antioxidant effects due to its chemical properties as a reducing agent, H2S induces vasorelaxation by interacting with a range of molecular targets. The mechanisms of action accounting for H2S-induced vasodilation include opening of vascular potassium channels (such as ATP-sensitive (KATP) and voltage-operated (Kv7) channels), inhibition of 5-phosphodiesterase (5-PDE), and activation of vascular endothelial growth factor receptor-2 (VEGFR-2). These effects may be attributed to H2S-induced S-persulfidation (or S-sulfhydration), which is a posttranslational modification of cysteine residues of many types of proteins resulting in structural and functional alterations (activation/inhibition). Thus, H2S donors, such as natural sulfur compounds, are promising antihypertensive agents with novel mechanisms of action.
... In addition, methionine enters into the methylation reaction of DNA. Brosnan and Brosnan (25) explained that methionine forms the amino acid cysteine inside the body and improves the immune status of birds. Methionine also enters the metabolic processes inside the body, where it works to balance other amino acids such as cysteine and participates In the synthesis of betaine, choline, vitamin B12, and folic acid metabolism (26); methionine is also an important source of sulfur inside the body and an influential donor of methyl groups that contribute to the formation of many vital compounds inside the body such as creatine and choline inside the body (27), that Amino acids in general and methionine, in particular, is essential for immunity and the formation of antibodies inside the body, especially when there is a pathological challenge, as indicated by Liu, Lu (28) that zincmethionine is used as a guide to the bioavailability of zinc in live animals, where the rate of zinc absorption increases when it binds with acids amino or proteins (29). ...
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Article
Abstract Nutritionists focused on introducing minerals as additives to poultry feed to achieve good bioavailability and increase absorption of these additives. Therefore, the current study aimed to demonstrate the effect of injecting hatching eggs with zinc methionine on the characteristics of hatched chicks and growth index. The hatching eggs injection technique was applied to inject the hatching eggs with zinc-methionine to study the traits of hatched chicks and the growth index of broilers where 300 eggs were used from the broiler breeder, and the eggs were divided into four treatments; each treatment of 75 eggs injected with zinc-methionine and at concentrations (0, 60, 80, 100 ppm) for the treatments T1, T2, T3, T4 respectively, and the studied traits were taken when the chicks hatched. The recorded data in this study showed that there was no significant effect on inactivity, general situation, case of yolk retracted inside the abdomen, abnormal checks, wing length and leg length, and significant improvement (P≤0.05) to T4 treatment in appearance and feather condition, Eye's appearance and Leg appearance meanwhile significant improvement (P≤0.05) to T3 treatment in naval case, residual yolk membrane, residual yolk and checks length, significant improvement of all Zn-methionine injection treatments in hatch window and total incubation period, significant improvement (P≤0.05) to T2, T4 treatments in growth hormone level in hatching.
... Therefore, the consequences of change to the DNA and RNA methylome and relationship to pathological processes is still unclear. However, the nonprotein, α-amino acid homocysteine, is an important intermediate in the one-carbon pathway which is essential for the production of methyl groups available for DNA/RNA methylation [77]. High homocysteine is also an established risk factor for both AD and TBI [78,39,79,80] and has been suggested to increase β-amyloid and tau pathology, protein aggregation as well as mitochondrial dysfunction involving oxidative stress pathways [81][82][83][84]. ...
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Preprint
Epigenetic processes have become increasingly relevant in understanding disease modifying mechanisms. 5-methylcytosine methylation of DNA (5mC) and RNA (m ⁵ C) have functional transcriptional and RNA translational consequences and are tightly regulated by writers, readers, and erasers effector proteins. To investigate the involvement of 5mC/5hmC and m ⁵ C effector proteins contributing to the development of dementia neuropathology, RNA-sequencing data for 32 effector proteins across four brain regions was examined in 51 aged non-affected and 56 Alzheimer’s disease (AD) individuals obtained from the Aging, Dementia and Traumatic Brain Injury (TBI) study. Gene expression profiles were compared between AD and controls, neuropathological Braak and CERAD scores and in individuals with a history of TBI. We found an increase in DNA methylation writers DNMT1 , DNMT3A , DNMT3B mRNA and decrease in reader UHRF1 mRNA in AD samples across three brain regions while the DNA erasers GADD45B and AICDA showed changes in mRNA abundance within neuropathological load groupings. RNA methylation writers NSUN6 and NSUN7 showed significant expression differences with AD and, along with the reader, ALYREF , differences in expression for neuropathologic ranking. A history of TBI was associated with a significant increase in the DNA readers ZBTB4 and MeCP2 ( p < 0.05) and decrease in NSUN6 ( p < 0.001) mRNA. These findings implicate regulation of protein pathways disrupted in AD and TBI via multiple pre- and post-transcriptional mechanisms including potentially acting upon tRNAs, enhancer RNAs, as well as nuclear-cytoplasmic shuttling and cytoplasmic translational control. The targeting of such processes provides new therapeutic avenues for neurodegenerative brain conditions.
... While Dmethionine hardly occurs in nature, L-methionine is a component of most proteins. Besides cysteine, methionine is the only proteinogenic amino acid containing sulfur [16]. Due to the thioether group, Methionine is less reactive than cysteine, whose sulfur atom is located in a sulfhydryl group. ...
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Article
Methionine is an essential amino acid, involved in the promotion of growth, immunity, and regulation of energy metabolism. Over the decades, research has long focused on the beneficial effects of methionine supplementation, while data on positive effects of methionine restriction (MR) were first published in 1993. MR is a low-methionine dietary intervention that has been reported to ameliorate aging and aging-related health concomitants and diseases, such as obesity, type 2 diabetes, and cognitive disorders. In addition, MR seems to be an approach to prolong lifespan which has been validated extensively in various animal models, such as Caenorhabditis elegans, Drosophila, yeast, and murine models. MR appears to be associated with a reduction in oxidative stress via so far mainly undiscovered mechanisms, and these changes in redox status appear to be one of the underlying mechanisms for lifespan extension and beneficial health effects. In the present review, the association of methionine metabolism pathways with redox homeostasis is described. In addition, the effects of MR on lifespan, age-related implications, comorbidities, and diseases are discussed.
... In contrast to the high protein content in soybeans, the sulfur-containing amino acids methionine and cysteine are deficient in monogastric diets and rations. Methionine cannot be synthesized in humans and monogastric animals and is considered an "essential" amino acid, and cysteine is a "conditionally" essential amino acid for animals that can convert methionine into cysteine in vivo (Brosnan and Brosnan, 2006). There is a negative influence from an inadequate intake of sulfur-containing amino acids on the growth and development of animals. ...
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Soybean proteins are limited by their low contents of methionine and cysteine. Herein, 7S globulin accumulation was reduced using RNA interference to silence CG-β-1 expression, and the content of the A2B1a subunit was largely increased under the soybean seed-specific oleosin8 promoter. The results showed that the sulfur-containing amino acid content in soybean seeds drastically improved, reaching 79.194 nmol/mg, and the 11S/7S ratio had a 1.89-fold increase compared to the wild-type acceptor. The secondary structures of 11S globulin were also altered, and the β-sheet content increased with decreasing β-turn content, which was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy and circular dichroism analysis. Our findings suggested that raising the accumulation of 11S glycinin at the expense of reducing the content of 7S globulin is an attractive and precise engineering strategy to increase the amount of sulfur-containing amino acids, and soybean proteins with A2B1a subunits of 11S isolates improved, and β-subunits of 7S fractions reduced simultaneously might be an effective new material for food production.
... Therefore, the consequences of change to the DNA and RNA methylome and relationship to pathological processes is still unclear. However, the nonprotein, α-amino acid homocysteine, is an important intermediate in the one-carbon pathway which is essential for the production of methyl groups available for DNA/RNA methylation [77]. High homocysteine is also an established risk factor for both AD and TBI [78,39,79,80] and has been suggested to increase β-amyloid and tau pathology, protein aggregation as well as mitochondrial dysfunction involving oxidative stress pathways [81][82][83][84]. ...
Full-text available
Preprint
Epigenetic processes have become increasingly relevant in understanding disease modifying mechanisms. 5-methylcytosine methylation of DNA (5mC) and RNA (m ⁵ C) have functional transcriptional and RNA translational consequences and are tightly regulated by writers, readers, and erasers effector proteins. To investigate the involvement of 5mC and m ⁵ C effector proteins contributing to the development of dementia neuropathology, RNA-sequencing data for 32 effector proteins across four brain regions was examined in 51 aged non-affected and 56 Alzheimer’s disease (AD) individuals obtained from the Aging, Dementia and Traumatic Brain Injury (TBI) study. Gene expression profiles were compared between AD and controls, neuropathological Braak and CERAD scores and in individuals with a history of TBI. We found an increase in DNA methylation writers DNMT1 , DNMT3A , DNMT3B mRNA and reader UHRF1 mRNA in AD samples across three brain regions. While DNA methyltransferases erasers GADD45B and AICDA showed changes in mRNA abundance within neuropathological load groupings. RNA methylation writers NSUN6 and NSUN7 showed significant expression differences with AD and, along with the reader, ALYREF , differences in expression for neuropathologic ranking. A history of TBI was associated with a significant increase in ZBTB4 ( p < 0.01) and decrease in NSUN6 ( p < 0.005) mRNA. These findings implicate regulation of protein pathways disrupted in AD and TBI via multiple pre- and post- transcriptional mechanisms including potentially acting upon tRNAs, enhancer RNAs, as well as nuclear-cytoplasmic shuttling and cytoplasmic translational control. The targeting of such processes provide new therapeutic avenues for neurodegenerative brain conditions.
... Of notice, methionine and cysteine/cystine metabolism are strictly interconnected, in absence of dietary cysteine/cystine, a substantial part of methionine should be transformed in cysteine/cystine unloading folates of methyl groups and forming homocysteine as metabolic intermediate. Cystine and cysteine being indistinguishable, since cystine is formed by two moieties of cysteine linked by a very labile hydrogen bond, spontaneously loosening up [66]. Certainly, focusing on single amino acids metabolism may be easiest and modulation of some amino acid intake helpful, but nitrogen intake in humans has also be considered in its complexity [67]. ...
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Protein-based structures are indispensable to maintain life, so identification and removal of worn out structures achieved through proteostasis, the sum of micro and macro-autophagy (autophagy) plus ubiquitin-proteasome system, must balance renewal by new synthesis. Many of the elements controlling dynamically equilibria between protein synthesis and protein degradation have been identified and modalities of activation actively studied, still we are quite far from mastering how this balance is ruled. Failure to maintain a positive balance between protein synthesis and protein degradation would result in sarcopenia, defined as the loss of skeletal muscle mass and function, a major clinical problem frequently accompanying chronic illnesses, but peculiarly spotted in cancer and in elderly patients. Also, how cancer is fed, and how nutrition in cancer patients may affect evolution and therapy effectiveness is another field of opinions and uncertainty. On the other hand, exercise and nutrition tailored to provide adequate amounts of amino acids are widely considered a necessary strategy for prevention and treatment of protein synthetic deficits in muscles. This paper will synthetically review how different nutritional strategies and energy production may interconnect efficiently synthesis and scavenging of aged and overused protein molecules by autophagy. Finally, since energy availability rules life and death of cells and organisms, an hypothesis predicting how energy may control the ratios among protein synthesis and autophagy is proposed: in normal conditions, protein syntheses have a key role in autophagy activation by consuming large amounts of energy when forming peptidic bonds, that is adenosine tri-phosphate (ATP) is consumed to mono-phospahate (AMP), thus decreasing ATP to AMP ratios. Conversely, both protein syntheses and autophagy may be scarcely activated when low availability of ATP would result also in lowest concentrations of AMP. In this peculiar setting, reduced rates of both protein syntheses and autophagy would be observed, resulting in worsening of protein balance and functions. Body Energy Needs and Protein Reservoirs Two tissues, skeletal appendicular muscles and skin comprise by weight the first and second major organs, and are also containers of the largest amounts of proteins in humans. Indeed, muscles should be considered also as organ acting as a reservoir of amino acids in a dynamic view of human metabolism requirements either in health or disease states, and it is so also in cancer [1].
... Two of the twenty amino acids used by life today as components of proteins contain sulfur: methionine and cysteine. Methionine is a key amino acid, given that it initiates nearly all protein sequences in eukaryotes; the presence of sulfur in cysteine allows for the formation of disulfide bridges, which aid in protein structure and folding [101]. Sulfur also plays a role in many coenzymes, including acetyl CoA, a central player in metabolism [102], as well as in many cofactors through iron-sulfur clusters. ...
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Biochemistry on Earth makes use of the key elements carbon, hydrogen, oxygen, nitrogen, phosphorus, and sulfur (or CHONPS). Chemically accessible molecules containing these key elements would presumably have been necessary for prebiotic chemistry and the origins of life on Earth. For example, feedstock molecules including fixed nitrogen (e.g., ammonia, nitrite, nitrate), accessible forms of phosphorus (e.g., phosphate, phosphite, etc.), and sources of sulfur (e.g., sulfide, sulfite) may have been necessary for the origins of life, given the biochemistry seen in Earth life today. This review describes potential sources of nitrogen-, sulfur-, and phosphorus-containing molecules in the context of planetary environments. For the early Earth, such considerations may be able to aid in the understanding of our own origins. Additionally, as we learn more about potential environments on other planets (for example, with upcoming next-generation telescope observations or new missions to explore other bodies in our Solar System), evaluating potential sources for elements necessary for life (as we know it) can help constrain the potential habitability of these worlds.
... Phosphatidylcholine is the predominant phospholipid in lipoproteins (Skipski et al., 1967), and is essential for hepatic export of triglycerides in very light density lipoproteins (Cole et al., 2012). Methionine also serves as a key precursor to intracellular antioxidants glutathione and taurine (Brosnan and Brosnan, 2006). Dysregulated lipid transport and antioxidant imbalance can both contribute to inflammation in the body (Drackley, 1999;Sordillo et al., 2009), so adequate methionine supply may help control inflammation in the body. ...
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Methionine supplementation can improve immune function in transition dairy cattle. Our objective was to determine if supplemental methionine could improve health and performance of newly received growing cattle. Crossbred heifers (n = 384; 222 kg initial body weight; southeastern U.S. origin) were received in 4 truckloads (blocks) over 9 d. Heifers were weighed at arrival. The following day (d 0) cattle were vaccinated for viral and clostridial diseases, received 2.5 mg tulathromycin/kg body weight, and were stratified within block by arrival body weight to 1 of 8 pens containing 12 heifers each. Within blocks, pens were assigned to 1 of 2 treatments: 0 (control) or 0.1725% Smartamine M to provide 0.1035% metabolizable methionine to the diet. Cattle were limit-fed at 2.2% of body weight daily (dry matter basis) a diet containing 40% wet corn gluten feed, 34.5% dry-rolled corn, 10% corn silage, 7.5% supplement, 4% alfalfa hay, and 4% prairie hay. Pen weights were measured weekly to determine feed offered the following week. Individual body weight and tail-vein blood samples were collected on d 0, 14, and 45. Plasma haptoglobin was measured to assess acute-phase protein response. Incidences of morbidity (1.6% for control, 2.6% for Smartamine M) and mortality (0.5% for both control and Smartamine M) were low. Between d 0 and 45, no differences were observed for average daily gain (1.24 vs. 1.27 kg/d; control vs. Smartamine M, P = 0.55) or gain:feed (0.107 vs. 0.110, P = 0.28), although dry matter intake was 1.3% greater (P < 0.01) for control than Smartamine M due to differences in diet dry matter concentration. An interaction between treatment and linear effect of day was detected for plasma haptoglobin (P < 0.05); over time, haptoglobin increased more for control (2.15, 2.28, and 2.95 mg/mL at 0, 14, and 45 d) than for Smartamine M (2.35, 2.37, and 2.58 mg/mL). Supplemental methionine may alleviate acute-phase protein responses in stressed receiving cattle.
... Glycine (NH 2 CH 2 COOH), which is unique because it has no isomeric forms and is a structural unit for many proteins, has been the subject of numerous studies (1). Sulfur-containing amino acids play major roles in synthesis, structure, and function of proteins (2). Sulfur is a critical element and it is found in the structure of cysteine and methionine, and it is necessary for the biosynthesis of sulfolipids, antioxidants, cofactors, secondary metabolites and amino acids (3,4). ...
... Of notice, methionine and cysteine/cystine metabolism are strictly interconnected, in absence of dietary cysteine/cystine, a substantial part of methionine should be transformed in cysteine/cystine unloading folates of methyl groups and forming homocysteine as metabolic intermediate. Cystine and cysteine being indistinguishable, since cystine is formed by two moieties of cysteine linked by a very labile hydrogen bond, spontaneously loosening up [66]. Certainly, focusing on single amino acids metabolism may be easiest and modulation of some amino acid intake helpful, but nitrogen intake in humans has also be considered in its complexity [67]. ...
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Protein-based structures are indispensable to maintain life, so identification and removal of worn out structures achieved through proteostasis, the sum of micro and macro-autophagy (autophagy) plus ubiquitin-proteasome system, must balance renewal by new synthesis. Many of the elements controlling dynamically equilibria between protein synthesis and protein degradation have been identified and modalities of activation actively studied, still we are quite far from mastering how this balance is ruled. Failure to maintain a positive balance between protein synthesis and protein degradation would result in sarcopenia, defined as the loss of skeletal muscle mass and function, a major clinical problem frequently accompanying chronic illnesses, but peculiarly spotted in cancer and in elderly patients. Also, how cancer is fed, and how nutrition in cancer patients may affect evolution and therapy effectiveness is another field of opinions and uncertainty. On the other hand, exercise and nutrition tailored to provide adequate amounts of amino acids are widely considered a necessary strategy for prevention and treatment of protein synthetic deficits in muscles. This paper will synthetically review how different nutritional strategies and energy production may interconnect efficiently synthesis and scavenging of aged and overused protein molecules by autophagy. Finally, since energy availability rules life and death of cells and organisms, an hypothesis predicting how energy may control the ratios among protein synthesis and autophagy is proposed: in normal conditions, protein syntheses have a key role in autophagy activation by consuming large amounts of energy when forming peptidic bonds, that is adenosine tri-phosphate (ATP) is consumed to mono-phospahate (AMP), thus decreasing ATP to AMP ratios. Conversely, both protein syntheses and autophagy may be scarcely activated when low availability of ATP would result also in lowest concentrations of AMP. In this peculiar setting, reduced rates of both protein syntheses and autophagy would be observed, resulting in worsening of protein balance and functions.
... LDHB could convert 3-mercaptopyruvic acid into 3-mercaptolactate. 20 After FA-30 treatment, LDHB was upregulated and its substrate 3-mercaptopyruvic acid was also upregulated, which may be due to the cervical cells reprogramming to promote their resistance to the severe microenvironments. 19,21 Six proteins including GARS, EPRS, NARS, YARS, WARS, and TARS, and three metabolites including proline, aspartic acid, and isoleucine were matched into the aminoacyl-tRNA biosynthesis pathway. ...
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The active ingredients of Traditional Chinese Medicine are an important source of bioactive molecules and play an important role in the research and development of innovative drugs. FA-30, which is a derivative of natural product ferulic acid, inhibited cervical cancer cell proliferation and induced apoptosis as well. To understand the underlying mechanisms of FA-30, a complementary multi-omics study was conducted. Cysteine and methionine metabolism and aminoacyl-tRNA biosynthesis pathways were significantly changed both at the metabolic level and proteomic level. This may help us to get a better understanding of cervical cancer and FA-30 at the same time.
... Li et al. [45] found that Arg played a key role in the proliferation of T and B cells in poultry. According to Calder [46], Arg is required for the synthesis of immune system proteins in turkeys, similarly to Met [47,48], which is why in this experiment neither high nor low ArgLysMet diets had a negative effect on the percentages of the analyzed T and B cell subpopulations in the spleen of turkeys. Other studies demonstrated that increased dietary Met content (by 0.60% relative to the control group where the recommended level of Met was applied) contributed to an increase in Met concentration in peripheral blood and in the percentages of CD4 + CD8α + T cell subpopulation in the thymus and the bursa of Fabricius in experimental birds [24,49]. ...
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Arginine (Arg), lysine (Lys), and methionine (Met) can be used to support the health status of turkeys. The present study investigated selected performance, gut integrity, and immunological parameters in turkeys reared in optimal or challenge conditions. The experiment lasted for 28 days, and it had a completely randomized 2 × 3 factorial design with two levels of dietary Arg, Lys and Met (high or low) and challenge with Clostridium perfringens (C. perfringens), Escherichia coli lipopolysaccharide (LPS) or no challenge (placebo). Increased dietary levels of Arg, Lys and Met had a beneficial effect on turkey performance and immunological parameters, and it improved selected indicators responsible for maintaining gut integrity in different challenge conditions. Under optimal conditions (with no challenge), high ArgLysMet diets did not compromise bird performance and they improved selected performance parameters in challenged birds. The immune system of turkeys was not excessively stimulated by high ArgLysMet diets, which did not disrupt the redox balance and had no negative effect on gut integrity. High ArgLysMet diets increased the expression levels of selected genes encoding nutrient transporters and tight junction proteins. However, the influence exerted by different dietary inclusion levels of Arg, Lys and Met on gut integrity was largely determined by the stressor (C. perfringens vs. LPS). Further studies are required to investigate the role of Arg, Lys and Met levels in the diet on the immune response, gut function and performance of turkeys in different challenge conditions.
... The cysteine thiol side chain participates in both enzymatic reactions by acting as a nucleophile and in structural stabilization of the proteins by forming disulphide bonds (Brosnan and Brosnan, 2006). In protozoan parasites like E. histolytica, cysteine has been shown to play a crucial role in growth, proliferation, pathogenesis, and antioxidative stress defence ( Jeelani et al., 2017( Jeelani et al., , 2014. ...
Article
African protected areas strive to conserve the continent's great biodiversity with a targeted focus on the flagship 'Big Five' megafauna. Though often not considered, this biodiversity protection also extends to the lesser-known microbes and parasites that are maintained in these diverse ecosystems, often in a silent and endemically stable state. Climate and anthropogenic change, and associated diversity loss, however, are altering these dynamics leading to shifts in ecological interactions and pathogen spill over into new niches and hosts. As many African protected areas are bordered by game and livestock farms, as well as villages, they provide an ideal study system to assess infection dynamics at the human-livestock-wildlife interface. Here we review five zoonotic, multi-host diseases (bovine tuberculosis, brucellosis, Rift Valley fever, schistosomiasis and cryptosporidiosis)-the 'Microscopic Five'-and discuss the biotic and abiotic drivers of parasite transmission using the iconic Kruger National Park, South Africa, as a case study. We identify knowledge gaps regarding the impact of the 'Microscopic Five' on wildlife within parks and highlight the need for more empirical data, particularly for neglected (schistosomiasis) and newly emerging (cryptosporidiosis) diseases, as well as zoonotic disease risk from the rising bush meat trade and game farm industry. As protected areas strive to become further embedded in the socio-economic systems that surround them, providing benefits to local communities, One Health approaches can help maintain the ecological integrity of ecosystems, while protecting local communities and economies from the negative impacts of disease.
... Methionine is an essential amino acid that serves an array of roles in both eukaryotes and prokaryotes. It is commonly known as the initiator of protein synthesis and plays an essential role as a methyl donor during the synthesis of fatty acids, polyamines, and biotin [1]. Its importance in cellular function makes its supplementation essential in animal feed as well as cell culture media. ...
Article
Methionine is an essential amino critical to many cell functions including the synthesis of proteins. Supplementation of methionine in vivo is typically through L-methionine, DL-methionine, or a methionine hydroxy analog (MHA). The goal of this study was to compare the function of L-methionine, DL-methionine, and an MHA as a source of methionine to myoblasts in vitro. Avian myoblasts isolated from turkey embryos were plated in media containing varying concentrations of DL-methionine (DLM; 1.125 mg/mL or 0.56 mg/mL) or methionine hydroxy analog (MHA; 1.28 mg/mL or 0.64 mg/mL) as well as a methionine deficient negative control group and an L-methionine supplemented positive control group. The results of the proliferation assay exhibited cell division in the absence of methionine which was not significantly different than the positive control group. Results from the myoblast fusion assay revealed significantly greater myotube diameter between methionine supplemented groups compared to the methionine deficient negative control. The findings of this study show an ability for avian myoblasts to proliferate in the absence of methionine, the significance of which is discussed. Additionally, findings from the fusion assay suggest that DL-methionine and MHA are potential cost-effective substitutes for methionine supplementation during terminal differentiation of avian myoblasts.
... Sulfur is an essential compound, primarily found in proteins with cysteine and methionine amino acids and sulfolipids. 2,35,36 Therefore, the presence of sulfur in lipids could lead to biased sulfur isotopic values in samples with high lipid content, as outlined earlier with carbon. ...
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RATIONALE The use of sulfur isotopes to study trophic ecology in marine ecosystems has increased in the last decade. Unlike other commonly used isotopes (e.g., carbon), sulfur can better discriminate benthic and pelagic productivity. However, how lipid extraction affects sulfur isotopic values has not been assessed, despite its frequent use to remove lipid effects on δ13 C values. Methods: We used white muscle and liver samples from two species of sharks and skin samples from two species of pinnipeds (sea lion and fur seal) to assess the effects of lipid extraction on stable isotope values for δ34 S, δ13 C, δ15 N. Isotopic values were determined by a continuous flow-isotope ratio mass spectrometer coupled to an elemental analyser (EA-IRMS). Results: Lipid extraction significantly decreased δ34 S values in shark tissues, more so for liver than muscle (-4.6 ± 0.9 vs -0.8 ± 0.3‰, average change), with nearly no alteration to their standard deviations. Lipid extraction did not affect δ34 S values from pinniped skin samples (0.2 ± 0.8‰, average change). After lipid extraction, consistent increases in δ13 C values (0.2-7.3‰) were detected as expected, especially in tissue with high lipid content (C:N > 4). After lipid extraction, significant increases in δ15 N values (0.5-1.4‰) were found in shark muscle and liver tissues. For pinniped skin samples, δ15 N values were not significantly lower after lipid extraction (-0.4 - -0.1‰). Conclusions: Lipid extraction did not have a strong impact on δ34 S values of shark muscle and pinniped skin (≤1‰). However, our results suggest it is essential to consider the effects of lipid extractions when interpreting results from δ34 S values of shark liver tissue, as they significantly depleted values relative to bulk tissue (~5‰). This may reflect selective removal of sulpholipids and glutathione present in higher concentrations in the liver than in muscle and skin and requires further investigation.
... Sulfur is one of the most important elements in the world, existing mainly in the form of amino acids and proteins [28]. Numerous organosulfur compounds are regularly used as pharmaceutical agents in daily life. ...
Article
In the past few decades, the chemistry of hypervalent iodine reagents has undergone a flourishing development in synthetic organic chemistry owing to their mild oxidative, low toxicity, air and moisture stability and environmentally benign features. A plethora of oxidative coupling reactions have been conducted using hypervalent iodine reagents as a nonmetallic oxidant. In particular, the C-S and C-Se bond forming reactions mediated by hypervalent iodine reagents have emerged as a powerful approach in the construction of S-containing and Se-containing heterocycles or building blocks. In these reactions, hypervalent iodine reagents behave as strong oxidants or electrophiles and activate the S-containing or Se-containing species to form more electrophilic cationic or radical intermediates which participate in subsequent coupling reactions. It is anticipated that this review summarizes all C–S and C-Se bonds forming reactions enabled by hypervalent iodine reagents under metal-free conditions.
... Almost all EAAs in carp body, except sulphur (S) containing AAs, decrease with decreasing natural food and increasing cereals in fishponds. S-containing AAs, methionine+ cysteine, are stored optimally only under a balanced diet because their storage in body at higher digestible intake increases risk of several toxic end-products (Baker, 2006;Brosnan and Brosnan, 2006). However, there are few EAAs apart from lysine that have a large share in carp body protein. ...
... The quite recent work by Jankowski et al. 55 pointed at rather beneficial effects of judicious increase in dietary Met content on the antioxidant defense system in turkeys. It has been also reported that L-methionine acts as L-Cys precursor-a potent antioxidant molecule 56 . ...
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The aim of the study was to determine how feeding rats a high-fat diet (F) supplemented with various forms of chromium affects the responses of the immune and redox systems, as well as epigenetic changes in the ileal tissue and the course of fermentation processes in the caecum. The rats received a pharmacologically relevant dose 0.3 mg Cr/kg body weight in form of chromium(III) picolinate (Cr-Pic), chromium (III)-methionine (Cr-Met), or chromium nanoparticles (Cr-NPs). The F increased DNA oxidation and raised the level of interleukin IL-6. The F was shown to reduce the intensity of fermentation processes in the caecum while increasing the activity of potentially harmful enzymes in the faeces. The addition of Cr in the form of Cr-NPs and Cr-Met in rats fed F beneficially increased mobilization of enzymes of the DNA repair pathway. All forms of Cr, but especially Cr-NPs, beneficially decreased the activity of caecal bacterial β-glucuronidase, faecal β-glucosidase and β-glucuronidase. However, due to the increase in level of cytokine IL-2 in small intestinal wall, induced by all tested forms of chromium, it is difficult to state conclusively that this element can mitigate unfavourable pro-inflammatory and oxidative changes induced by a F in the small intestinal wall.
... Se encuentra presente en cantidades relativamente altas en la retina y los tejidos musculares esquelético y cardíaco [10]. La taurina deriva del metabolismo de la cisteína y es sintetizada en el hígado a través de varias etapas enzimáticas, por consiguiente, se considera no esencial o condicionalmente esencial [11]. ...
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RESUMEN Con este estudio se pretende evaluar si la taurina (un aminoácido antioxidante) es capaz de proteger el músculo esquelético de ratas en desarrollo de los efectos citotóxicos de la hiperoxia postnatal. Para esto, dos grupos de ratas recién nacidas de la cepa Sprague-Dawley fueron expuestas a hiperoxia junto con su madre, desde su nacimiento hasta el día P6, P9 y P12. La madre de uno de los grupos tomó solución de taurina al 3% como agua de beber y la madre del otro grupo tomó solo agua. Dos grupos similares, pero sin hiperoxia fueron utilizados como controles. Para los análisis bioquímicos e histológicos se utilizó el músculo gastrocnemio de los miembros traseros. El estrés oxidativo se evaluó mediante la técnica de análisis de sustancias reactivas del ácido tiobarbitúrico (TBARS), por métodos espectrofotométricos, mientras que para la histología se aplicó la técnica de embebido en plástico. La concentración de TBARS en el grupo hiperoxia fue significativamente superior a la de los demás grupos comparados. El grupo hiperoxia también presentó daños estructurales y los más notables fueron el edema intersticial y deformación en los fascículos de fibras musculares. En el grupo hiperoxia-taurina disminuyeron significativamente los niveles de TBARS y no se presentaron problemas de edema ni malformaciones en los fascículos musculares. En conjunto, los resultados arrojaron que la taurina controla el estrés oxidativo y protege la estructura del músculo esquelético durante la hiperoxia postnatal. Palabras claves: Músculo gastrocnemio, estrés oxidativo, taurina, TBARS, prematuro. Histopathology, TBARS concentration and total protein level of skeletal muscle in newborn rats exposed to hyperoxia and the protective effect of taurine ABSTRACT This study aims to evaluate whether taurine (an antioxidant amino acid) is able to protect developing rat skeletal muscle from the cytotoxic effects of postnatal hyperoxia. For this, two groups of newborn Sprague-Dawley strain rats were exposed to hyperoxia together with their mother, from birth until day P6, P9 and P12. The mother of one group drank 3% taurine solution as drinking water and the mother of the other group only drank water. Two similar groups, but without hyperoxia, were used as controls. For biochemical and histological analysis, the gastrocnemius muscle of the hind limbs was utilised. Oxidative stress was evaluated using the thiobarbituric acid reactive substance analysis technique (TBARS), by spectrophotometric methods, while the plastic embedding technique was applied for histology. The concentration of TBARS in the hyperoxia group was significantly higher than that of the other groups compared. The hyperoxia group also presented structural damage and the most notable were interstitial edema and deformation in the fascicles of muscle fibers. In the hyperoxia-taurine group, TBARS levels decreased and structurally there were no problems of edema and malformations in the muscle. Overall, the results showed that taurine controls oxidative stress and protects skeletal muscle structure during postnatal hyperoxia. INTRODUCCIÓN Cada año nacen en el mundo unos 15 millones de bebés antes de llegar a término y aproximadamente un millón de ellos debido a complicaciones en el alumbramiento [1]. Muchos de los bebés prematuros que sobreviven padecen algún tipo de discapacidad de por vida, en particular, las relacionadas con el aprendizaje, problemas visuales y auditivos [2, 3].
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Corynebacterium glutamicum has been widely utilized for the industrial production of various amino acids. Trehalose is a prerequisite for the biosynthesis of mycolates which are structurally important constituents of the cell envelope in C. glutamicum. In this study, C. glutamicum mutant ΔSYA, which is unable to synthesize trehalose was constructed by deleting genes treS, treY and otsA in the three pathways of trehalose biosynthesis. In the fermentation medium, ΔSYA grew as well as the control C. glutamicum ATCC13869, synthesized similar levels of glucose monocorynomycolate, trehalose dicorynomycolate, and phospholipids to ATCC13869, but produced 12.5 times more L-glutamate than ATCC13869. Transcriptional levels of the genes relevant to L-arginine biosynthesis, encoding ODHC and relevant to the biosynthesis of sulfur-containing amino acids were down-regulated in ΔSYA. In minimal medium with different concentrations of glucose, ΔSYA grew worse than ATCC13869 but excreted more L-glutamate. When grown in minimal medium, phospholipids are the major lipid in ΔSYA, while glucose monocorynomycolate, trehalose dicorynomycolate, and phospholipids are the major lipid in ATCC13869. The transcriptional levels of mscCG in ΔSYA was significantly up-regulated when grown in minimal medium.
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The paper shows the effective utilization of non-degradable waste material like the hair of humans, Expanded Polystyrene Spheres (EPS), and rice husk fly ash to a final product Fiber-reinforced concrete panel. Concrete fracture, catastrophic failure, spalling of concrete and non-quake resistance, with the application of a load are major problems of the current scenario in the concrete world (Mindess, 2009). This paper tries to solve this type of problem by using the natural fibers and some additives which are under patient right. The researcher of this paper has developed a prefab panel which may be the substitute product of brick, ACC block, interlocking block, EPS panel, and local prefab panel. The utilization of industrial waste to usable products for construction is a major challenge that the researcher has taken. The paper shows that product can be made economical and able to reduce environmental challenges. Ingredients like human hair, EPS, chemical agent, cement, fly ash, water, and fiberboard are utilized in a certain time and fixed condition to complete the formation of the Fiber-reinforced concrete panel. The panel was found to have multi-function like a light in weight, fireproof, and flexibility which was its main USP (Unique Selling Point). The researcher thinks this product might change the perception of Nepalese customer, who thinks prefab as a costly and less strength product. Nepal political instability and dependent culture on foreign country shows an impossible possibility to use an artificial fiber and imported fly ash (ITC, 2017). This paper also presents the Nepalese market perception through the business model canvas, a business strategy that can be taken, hindrance, and the possibility to use human hair fiber, fly ash and recycled EPS to complete finished goods.
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Plant protein sources play an essential role in aquaculture by reducing the use of fish meal to sustainable levels, although further supplementation is needed to fulfill fish nutritional requirements. This work addressed fish growth performance and proteome changes to dietary methionine in European seabass juveniles. A dose-dependent response to methionine (Met) was observed on fish growth consistent with proteomic analyses, 0.9% (w/w). Fish fed at 0.77% (w/w) exhibited reduced growth and an enrichment in proteins involved in cellular homeostasis. Proteomics data suggest an optimal nutritional status at 1.36% Met (w/w), together with putative beneficial effects on the immune system up to 1.66% Met (w/w). The response to dietary Met involved the convergence of different metabolic and signalling pathways implicated in cell growth and immune response e.g., mTOR, Hedgehog or the T Cell receptor signalling, coupled with a fine-tuning regulation of amino acid metabolism and translation.
Chapter
Cysteine is a sulfur-containing, α-amino acid with the chemical formula O2CCH(NH2)CH2SH. Cysteine is unique amongst the 20 natural amino acids as it contains a thiol group. It is classified as a conditionally non-essential amino acid since the human body can naturally synthesize it [1, 2]. Like other amino acids, cysteine has an amphoteric character and is extensively used as an additive in the food industry, mainly in bakery, in the production of flavors, and as a processing aid [3]. When used as a food additive, it is labeled as E920 [4].
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Nitrate is used as a methane inhibitor while cysteamine is considered as a growth promoter in ruminants. The present study evaluated the effect of sodium nitrate and cysteamine on methane (CH4) production, rumen fermentation, amino acid (AA) metabolism, and rumen microbiota in a low protein diet. Four treatments containing a 0.5 g of substrate were supplemented with 1 mg/mL sodium nitrate (SN), 100 ppm cysteamine hydrochloride (CS), and a combination of SN 1 mg/mL and CS 100 ppm (CS+SN), and a control (no additive) were applied in a completely randomized design. Each treatment group had five replicates. Two experimental runs using in vitro batch culture technique were performed for two consecutive weeks. Total gas and CH4 production were measured in each fermentation bottle at 3, 6, 9, 12, 24, 48, and 72 h of incubation. The results showed that SN and CS+SN reduced the production of total gas and CH4, increased the rumen pH, acetate, acetate to propionate ratio (A/P), and microbial protein (MCP) contents (p < 0.05), but decreased other volatile fatty acids (VFA) and total VFA (p = 0.001). The CS had no effect on CH4 production and rumen fermentation parameters except for increasing A/P. The CSN increased the populations of total bacteria, fungi, and methanogens but decreased the diversity and richness of rumen microorganisms. In conclusion, CS+SN exhibited a positive effect on rumen fermentation by increasing the number of fiber degrading and hydrogen-utilizing bacteria, with a desirable impact on rumen fermentation while reducing total gas and CH4 production.
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This book discusses the latest advances in cotton genetics and the biochemistry, physiology, bioinformatics, and genomics of the cotton plant. Chapters cover genomics and transcriptomics approaches to characterization and tagging of essential genes, novel transgenic tools to accelerate breeding against climate issues, abiotic and biotic stress pressures, biological control and machinery tools for cotton plant protection, cotton seed meal production, and sustainable and effective farming in the era of climate change and technological advance.
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One-carbon metabolism is a key metabolic network that integrates nutritional signals with embryonic development. However, the response of one-carbon metabolism to methionine status and the regulatory mechanisms are poorly understood. Herein, we found that methionine supplementation during pregnancy significantly increased fetal number and average fetal weight. In addition, methionine modulated one-carbon metabolism primarily through two metabolic enzymes, cystathionine β-synthase (CBS) and methionine adenosyltransferase 2A (MAT2A), which were significantly increased in fetal liver tissues and porcine trophoblast (pTr) cells in response to proper methionine supplementation. CBS and MAT2A overexpression enhanced the DNA synthesis in pTr cells. More importantly, we identified a transcription factor, DNA damage-inducible transcript 3 (DDIT3), that was the primary regulator of CBS and MAT2A, which bound directly to promoters and negatively regulated the expression of CBS and MAT2A. Taken together, our findings identified that DDIT3 targeting on CBS and MAT2A was a novel regulatory pathway that mediated cellular one-carbon metabolism in response to methionine signal and provided promising targets to improve pregnancy health.
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A metal-free method for the regioselective synthesis of 2-thiolated quinolines from quinoline N-oxides in water at room temperature is developed. The reaction is conducted using benzenethiols as thiolation reagents in the presence of p-toluenesulfonyl chloride via p-toluenesulfonyl chloride-assisted tandem C-H bond activation, nucleophilic addition, deoxygenation and aromatization processes. This method does not require the use of metal catalysts and oxidants. It shows the advantages of wide functional group tolerance, short reaction times and simple operation.
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Selenomethionine (SeMet) randomly replaces methionine (Met) in protein translation. Because of strongly differing redox properties of SeMet and Met, SeMet mis-incorporation may have detrimental effects on protein function, possibly compromising the use of nutritional SeMet supplementation as an anti-oxidant. Studying the functional impact of SeMet in proteins on a cellular level is hampered by the lack of accurate and efficient methods for estimating the SeMet incorporation level in individual viable cells. Here we introduce and apply a method to measure the extent of SeMet incorporation in cellular proteins by utilizing a genetically encoded fluorescent methionine oxidation probe. Supplementation of SeMet in mammalian culture medium resulted in >84% incorporation of SeMet, and SeMet labeling as low as 5% was readily measured. Kinetics and extent of SeMet incorporation on the single-cell level under live-cell imaging conditions provided direct access to protein turn-over kinetics and SeMet redox properties in a cellular context. The method is furthermore suited for experiments utilizing high-throughput fluorescence microplate readers or fluorescence-activated cell sorting (FACS) analysis.
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Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis (AS). If these conditions are disordered, it will inevitably lead to plaque formation and even rupture. Astragaloside IV (AsIV) and salvianolic acid B (Sal B) are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza, respectively, and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies. However, it is still unknown if the combination of AsIV and Sal B (AsIV + Sal B) can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect. To clarify the role of AsIV + Sal B in AS, we observed the efficacy of each group (Control, Model, AsIV, Sal B, and AsIV + Sal B) by biomolecular assays, such as observing the pathological morphology of the aorta by oil red O staining, evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test, and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS. Results showed that AsIV, Sal B and AsIV + Sal B decreased the deposition of lipid in the arterial wall, so as to exert the effect of anti-oxidant stress and vascular endothelial protection, where the inhibitory effect of AsIV + Sal B was the most obvious. Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline. AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism. AsIV + Sal B is mainly related to the regulation of the citrate cycle (TCA cycle), alanine, aspartic acid, and glutamate metabolism, cysteine, and methionine metabolism. Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination. In conclusion, we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS, and succinic acid and methionine are the synergistic metabolites.
Article
Nitric oxide depletion secondary to arginase induced arginine deficiency has been shown to be important in the pathophysiology of vaso-occlusion in sickle cell pain crisis. Our objective of this study was to perform a comprehensive amino acid evaluation during sickle cell pain crisis. In a total of 58 subjects (29 in steady-state sickle cell disease and 29 with sickle cell pain crisis), the amino acids related to nitric oxide pathway was significantly decreased during sickle cell pain crisis compared to steady-state sickle cell disease: arginine (p = 0.001), citrulline (p = 0.012), and ornithine (p = 0.03). In addition, the amino acids related to energy metabolism was significantly decreased during a pain crisis: asparagine (p < 0.001), serine (p = 0.002), histidine (p = 0.017), alanine (p = 0.004), tyrosine (p = 0.012), methionine (p = 0.007), cystine (p = 0.016), isoleucine (p = 0.016) and lysine (p = 0.006). The amino acid related to oxidative stress were significantly higher during a sickle cell pain crisis (glutamic acid (p < 0.001). Furthermore, multivariate analysis with partial least squares-discriminant analysis (PLS-DA) showed that deficiencies of the amino acids arginine, asparagine, citrulline, methionine and alanine were the most important related to sickle cell pain crisis.
Article
Maternal cannabis use during lactation may expose developing infants to cannabinoids (CBs) such as ∆-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBs modulate lipid signaling molecules in the central nervous system in age- and cell-dependent ways, but their influence on the lipid composition of breast milk has yet to be established. This study investigates the effects of THC, CBD, or their combination on milk lipids by analyzing the stomach contents of CD1 mouse pups that have been nursed by dams injected with CBs on postnatal days (PND) 1 -10. Stomach contents were collected 2 hours after the last injection on PND10 and HPLC/MS/MS was used to identify and quantify over 80 endogenous lipid species and cannabinoids in the samples. We show that CBs differentially accumulate in milk, lead to widespread decreases in free fatty acids, decreases in N-acyl methionine species, increases N-linoleoyl species, as well as modulate levels of endogenous CBs (eCBs) AEA, 2-AG, and their structural congeners. Our data indicate the passage of CBs to pups through breast milk and that maternal CB exposure alters breast milk lipid compositions.
Article
Cysteine plays a versatile role in cellular physiology and has previously been shown to be instrumental to Mycobacterium tuberculosis (M.tb) pathophysiology. In this study, we have generated mutants deficient in CysK2 and CysH, the key Cysteine, biosynthetic enzymes. In contrast to the ΔcysH mutant, the ΔcysK2 mutant is not an auxotroph and as such not essential for cysteine biosynthesis. Interestingly, the ΔcysK2 mutant shows increased sensitivity to cumene hydroperoxide, vitamin C, diamide, rifampicin and Vancomycin and shows alterations in phospholipid profile of Mtb cell wall. Our findings suggest that alteration in phospholipids content of M.tb cell wall by CysK2 may form a mode of defence against selected antibiotics and oxidative stress.
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The paper shows the effective utilization of non-degradable waste material like the hair of humans, EPS, and rice husk fly ash to a final product Fiber-reinforced concrete panel. A problem like a concrete fracture, catastrophic failure, spalling of concrete and non-quake resistant, with the application of a certain load is a major problem of the current scenario in the concrete world (Mindess, 2009). This paper tries to solve this type of problem by using the natural fibers and some additives which are under patient right. The researcher of this paper has developed a prefab panel which may be the substitute product of brick, ACC block, interlocking block, EPS panel, and local prefab panel. The utilization of industrial waste to usable products for construction is a major challenge that the researcher has taken. The paper shows the product can be made economical and able to reduce environmental challenges. Ingredients like human hair, EPS, chemical agent, cement, fly ash, water, and fiberboard are utilized in a certain time and fixed condition to complete the formation of the Fiber-reinforced concrete panel. The panel was found to have multi-function like a light in weight, fireproof, and flexibility which was its main USP (Unique Selling Point). The researcher thinks this product might change the perception of Nepalese customer, who thinks prefab as a costly and strength less product. Nepal political instability and dependent culture to foreign country shows an impossible possibility to use an artificial fiber and imported fly ash (ITC, 2017). This paper also presents the Nepalese market perception through the business model canvas, a business strategy that can be taken, hinderance, and the possibility to use human hair fiber, fly ash and recycled EPS to complete finished goods.
Article
Trypanosomatids are mainly responsible for heterogeneous parasitic diseases: Leishmaniasis, Sleeping sickness, and Chagas disease and control of these diseases implicates serious challenges due to the emergence of drug resistance. Redox-active biomolecules are the endogenous substances in organisms, which play important role in the regulation of redox homeostasis. The redox-active substances like glutathione, trypanothione, cysteine, cysteine persulfides, etc., and other inorganic intermediates (hydrogen peroxide, nitric oxide) are very useful as defence mechanism. In the present review, the suitability of trypanothione and other essential thiol molecules of trypanosomatids as drug targets are described in Leishmania and Trypanosoma. We have explored the role of tryparedoxin, tryparedoxin peroxidase, ascorbate peroxidase, superoxide dismutase, and glutaredoxins in the anti-oxidant mechanism and drug resistance. Up-regulation of some proteins in trypanothione metabolism helps the parasites in survival against drug pressure (sodium stibogluconate, Amphotericin B, etc.) and oxidative stress. These molecules accept electrons from the reduced trypanothione and donate their electrons to other proteins, and these proteins reduce toxic molecules, neutralize reactive oxygen, or nitrogen species; and help parasites to cope with oxidative stress. Thus, a better understanding of the role of these molecules in drug resistance and redox homeostasis will help to target metabolic pathway proteins to combat Leishmaniasis and trypanosomiases.
Thesis
In this thesis, the syntheses of novel ligands of the Bitter Taste Receptor TAS2R14 using flufenamic acid as lead structure is described: By synthesizing a compound library consisting of 94 flufenamic acid analogues, a deep insight into the receptors binding pocket was given and the lead structure’s functional properties could be evaluated. Introducing substituents to both aromatic cores revealed derivatives with improved pharmacological activity but also inhibitory and inverse agonistic functions. Replacement of the carboxylic acid moiety by non-acidic groups or bioisosteres demonstrated the importance of the acidic moiety but also highlighted the influence of geometry, pKa and partial charge distribution on the ligand’s activity. The most crucial advance in these investigations surely is represented by 5-substituted tetrazoles as carboxylic acid bioisosteres in combination with a 2-aminopyrimidine motif as ring B substitution. This pattern had major impact on the intrinsic activity of the ligand and could display an interesting opportunity for future investigations.
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Methionine is an essential amino acid that contributes to protein formation, fetal development, and milk synthesis. Thus, we hypothesized that a supplementation with Optimethione® during the last third of gestation in female goats will increase the maternal body live weight, the milk yield and milk composition and the offspring weight and body mass index at birth and postnatal performance. We fed (n = 30) or not (n = 30) herbal methionine Optimethione® to pregnant mul-tiparous Alpine goats from gestational day 100 until delivery. We evaluated the productive var-iables from the dams and offspring. Maternal intake of herbal methionine Optimethione® dur-ing pregnancy did not increase the live weight or increase the milk yield and composition. However, the tested offspring variables were influenced by the maternal intake of herbal me-thionine Optimethione® during gestation by improving the birth weight, body mass index, and postnatal growth pattern. An increase in birth weight would be expected to increase neonatal survival up to weaning. Moreover, a relative fatness is required for reproductive success; thus, offspring that are born heavier and bigger can display a faster postnatal growth and accelerate the onset of puberty and increase reproductive success.
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The current study was carried out to detect the effect of dietary guanidinoacetic acid (GAA) supplementation on carcass characteristics and meat quality in finishing pigs fed different dietary crude protein (CP) levels. Sixty-four barrows with an initial body weight of 73.05 ± 2.34 kg were randomly allocated into 1 of 4 dietary treatments in a 2 (100% vs. 125% NRC CP level) × 2 (0 vs. 300 mg/kg GAA) factorial arrangement (n = 7). The feeding trial lasted for 49 d. GAA supplementation significantly reduced drip loss (P = 0.01), free water distribution (T23 peak area ratio) (P = 0.05) and the concentrations of free alanine, threonine, methionine and isoleucine (P < 0.05); but increased total glycine content (P = 0.03) in the longissimus dorsi muscle of finishing pigs regardless of the dietary CP levels. Furthermore, primary myogenic cell differentiation system was employed to investigate the influence of inclusion of GAA on free amino acid concentrations in myotubes (n = 4) and validate the finding in the animal feeding trial. We found that GAA inclusion in culture medium also decreased intracellular concentrations of free alanine, threonine, methionine, isoleucine, valine and proline in differentiated primary myogenic cells in vitro (P < 0.05). Meanwhile, relative to diets with 100% NRC CP level, the intake of diets with 125% NRC CP level improved sarcoplasmic protein solubility, increased the contents of carnosine and total free amino acids as well as flavor amino acids in the longissimus dorsi muscle and decreased backfat thickness at the 6–7th ribs in pigs (P < 0.05). In addition, we observed that the impact of dietary GAA supplementation on the last rib fat thickness, shear force, and free lysine content in the longissimus dorsi muscle was dependent on dietary CP levels (P < 0.05). Collectively, dietary GAA supplementation can reduce drip loss, decrease the concentrations of free amino acids and flavor amino acids of fresh meat independent of dietary CP levels.
Article
To study the effects of dietary methionine on growth performance, immunity, antioxidant capacity, protein metabolism, inflammatory response and apoptosis factors in Chinese mitten crabs (Eriocheir sinensis). Five diets with different methionine levels (0.63%, 0.85%, 1.06%, 1.25% and 1.47%) were fed to E. sinensis for 8 weeks. Results showed that in the 1.25% Met group, both growth performance and feed utilization were significantly increased. The crude protein content of crab muscle in the 1.06% and 1.25% Met groups was significantly higher than that in the control group. The immune and antioxidant enzyme activities, as well as gene expression levels of anti-lipopolysaccharide factor 1 (ALF1), Crustin-1, prophenoloxidase (proPO), cap ‘n’ collar isoform C (CncC) in 1.25% Met group were significantly higher than other groups. The activities of adenosine deaminase (ADA) and glutamate transaminase (GPT) in serum decreased first and then increased with the increase of methionine content, while the changes of ADA and GPT in hepatopancreas increased first and then decreased. 1.25% Met group exhibited significantly increased levels of GOT, GPT, and ADA compared to the control group. 1.25% Met diet group significantly up-regulated protein synthesis and anti-apoptotic factors, and significantly down-regulated inflammatory and pro-apoptotic factors in hepatopancreas. At 1.25% in the diet, methionine was found to boost E. sinensis growth, muscle protein deposition and immunity, as well as its antioxidant capacity. Combined with the above results, based on the expression of factors involved in the mammalian target of rapamycin (mTOR) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway, it is proved that methionine can not only promote protein metabolism, improve feed utilization, but also alleviate the inflammatory response and apoptosis caused by oxidative stress in the body.
Chapter
Cotton, which is one of the leading fiber and oilseed crops, consumes 16% of the total pesticides and about 24% of insecticides in the world. In arid climatic regions such as Turkey, most of the plant water consumption is met by surface irrigation methods, while a significant part of it infiltrates deep. During cultivation, a significant portion of pesticides and chemical fertilizers are consumed incorrectly, or unconsciously due to socioeconomic and cultural reasons such as the lack of education of farmers and low economic income. For this reason, it is necessary to understand the correct cultivation techniques from planting to harvest and to manage critical periods in practice. Owing to this, it is necessary to re-evaluate and sustain high-productivity and quality cotton cultivation together with human and environmental requirements. Especially for this purpose, the charts and figures prepared to give direction to experts are a tool for a correct and complete understanding of the topics covered. Considering the objectives and needs of agricultural production, the analysis of the most critical issues required for cotton cultivation from a different perspective will be an important stage for the next steps.
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Abstract: Sugarcane is cultivated mainly for its high sucrose content but it can also produce many metabolites with promising antioxidant potential. However, very few studies have been reported on the biosynthesis of metabolites in sugarcane to date. In this study, we have identified a wide range of amino acids and organic acids in the rind of six sugarcane varieties by the LC-MS/MS method. A total number of 72 amino acids and 55 organic acid compounds were characterized; among these, 100 were reported for the first time. Moreover, 13 amino acids and seven organic acids were abundantly distributed in all varieties tested and considered major amino acids and organic acids in sugarcane. The variety Taitang134 (F134) showed the highest content of total amino acids, whereas the varieties ROC16 and Yuetang93/159 (YT93/159) had maximum content of organic acids. The amino acids of the rind extract presented higher antioxidant capacity than the organic acids of the rind extract. In addition, the transcriptomic and metabolic integrated analysis highlighted some candidate genes associated with amino acid biosynthesis in sugarcane. We selected a transcription factor gene, MYB(t), and over-expressed it in Arabidopsis. The transgenic plants showed a higher accumulation of amino acids with higher antiradical activity compared with the wild-type Arabidopsis plants. Thus, we characterize a wide range of amino acids and organic acids and their antiradical activities in different sugarcane varieties and present candidate genes that can be potentially valuable for the genetic improvement of metabolites in sugarcane bagasse.
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The literature on sulfur amino acid metabolism is too vast for a short chapter to cover in great depth. I attempt here a brief overview with references to many specialized review articles. This review emphasizes aspects of sulfur amino acid metabolism elucidated in the last ten years, in particular aspects not generally covered in biochemistry texts, e.g. transaminative pathways of methionine metabolism. A selected list of reviews is given in references 1-15. References to reviews on glutathione are covered in the chapter by A. Meister in this volume (1a).
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Article
Cysteine and methionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they can form disulfide bonds that contribute to protein structure. In contrast, the specific functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, available as an efficient oxidant scavenger. Reduction back to methionine by methionine sulfoxide reductases would allow the antioxidant system to function catalytically. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the 16 methionine residues could be oxidized with little effect on catalytic activity of the enzyme. The oxidizable methionine residues were found to be relatively surface exposed, whereas the intact residues were generally buried within the core of the protein. Furthermore, the susceptible residues were physically arranged in an array that guarded the entrance to the active site.
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Article
We propose a simple mathematical model of liver S -adenosylmethionine (AdoMet) metabolism. Analysis of the model has shown that AdoMet metabolism can operate under two different modes. The first, with low metabolic rate and low AdoMet concentration, serves predominantly to supply the cell with AdoMet, the substrate for various cellular methylation reactions. The second, with high metabolic rate and high AdoMet concentration, provides an avenue for cleavage of excess methionine and can serve as a source of cysteine when its increased synthesis is necessary. The switch that triggers interconversion between the "low" and "high" modes is methionine concentration. Under a certain set of parameters both modes may coexist. This behavior results from the kinetic properties of (i) the two isoenzymes of AdoMet synthetase, MATI and MATIII, that catalyse AdoMet production; one is inhibited by AdoMet, whereas the other is activated by it, and (ii) glycine- N -methyltransferase that displays highly cooperative kinetics that is different from that of other AdoMet-dependent methyltransferases. Thus, the model provides an explanation for how different cellular needs are met by regulation of this pathway. The model also correctly identifies a critical role for glycine N -methyltransferase in depleting excess methionine in the high mode, thus avoiding the toxicity associated with elevated levels of this essential amino acid.
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Article
We have analyzed existing methodologies and created novel methodologies for the automatic assignment of S-adenosylmethionine (AdoMet)-dependent methyltransferase functionality to genomic open reading frames based on predicted protein sequences. A large class of the AdoMet-dependent methyltransferases shares a common binding motif for the AdoMet cofactor in the form of a seven-strand twisted beta-sheet; this structural similarity is mirrored in a degenerate sequence similarity that we refer to as methyltransferase signature motifs. These motifs are the basis of our assignments. We find that simple pattern matching based on the motif sequence is of limited utility and that a new method of "sensitized matrices for scoring methyltransferases" (SM2) produced with modified versions of the MEME and MAST tools gives greatly improved results for the Saccharomyces cerevisiae yeast genome. From our analysis, we conclude that this class of methyltransferases makes up approximately 0.6-1.6% of the genes in the yeast, human, mouse, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, and Escherichia coli genomes. We provide lists of unidentified genes that we consider to have a high probability of being methyltransferases for future biochemical analyses.
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Article
Native disulphide bonds are essential for the structure and function of many membrane and secretory proteins. Disulphide bonds are formed, reduced and isomerized in the endoplasmic reticulum of mammalian cells by a family of oxidoreductases, which includes protein disulphide isomerase (PDI), ERp57, ERp72, P5 and PDIR. This review will discuss how these enzymes are maintained in either an oxidized redox state that allows them to form disulphide bonds in substrate proteins or a reduced form that allows them to perform isomerization and reduction reactions, how these opposing pathways may co-exist within the same compartment and why so many oxidoreductases exist when PDI alone can perform all three of these functions.
Chapter
Adequate dietary methionine is necessary for the normal growth and development of mammals. This essential role derives from the involvement of the amino acid, or its metabolic products, in several fundamental biologic processes. These include protein synthesis; the synthesis of S-adenosylmethionine (AdoMet), which is utilized both by multiple transmethylation reactions and in the formation of the polyamines spermidine and spermine; and the synthesis of homocysteine. In turn, the latter compound participates in three essential reactions or sequences: (1) the transsulfuration pathway, which leads to the formation of cystathionine, cysteine, glutathione, and other metabolically important metabolites; (2) the recycling of intracellular folates; and (3) the catabolism of choline and betaine.
Article
Amino acid concentrations in whole blood, liver, kidney, skeletal muscle, and brain were measured and arteriovenous differences calculated for head, hindlimb, kidney, gut, and liver in control and streptozotocin-diabetic rats. In the control rats, glutamine was released by muscle and utilized by intestine, intestine released citrulline and alanine, liver removed alanine, and the kidneys removed glycine and produced serine. In diabetic rats the major changes from the pattern of fluxes seen in the normal rat were the release of many amino acids from muscle, with glutamine and alanine predominating, and the uptake of these amino acids by the liver. Glutamine removal by the intestine was suppressed in diabetes, but a large renal uptake of glutamine was evident. Branched-chain amino acids were removed by the diabetic brain, and consequently, brain levels of a number of large neutral amino acids were decreased in diabetes.
Article
Estimates of the daily rate of methionine utilization by adult humans, published previously, were under-estimated because available data did not permit quantitative assessment of the rate at which the methyl moiety of methionine is oxidized.1 The present paper reports efforts to measure the rate of oxidation of methionine methyl by the two pathways that proceed through the intermediate N-methylglycine (sarcosine). Two sarcosinemic, sarcosinuric patients, proven or presumed to have specific genetic defects in the sarcosine-oxidizing system, were studied while maintained on constant diets containing differing amounts of methionine, choline (or choline derivatives), and glycine. The steadystate excretions of sarcosine, creatinine, creatine, and a number of other materials were determined. The results obtained suggest that sarcosine is formed in 2 ways: (1) In an amount equivalent to the dietary intake of choline (or choline derivative)—this pathway would make a net positive contribution to the methionine-methyl pool due to the transfer of a methyl group from betaine to homocysteine; and (2) By processes requiring net consumption of methionine methyl. For the single patient for whom reasonably complete data were attained, it appears that 2 such processes may be occurring. One proceeds at a rate (approximately 2 mmole/24 hr) that changed little as total intake of labile methyl groups∗ was altered. The second became prominent (and accounted for the bulk of the incremental intake of labile methyl groups) when this intake exceeded the combined amounts required for the synthesis of creatine (10.2 mmole/24 hr), other transmethylation reactions (1.4 mmole/24 hr), polyamine synthesis (0.5 mmole/24 hr), and the “basal” process of sarcosine formation just mentioned (2 mmole/24 hr). It is possible that such “basal” sarcosine formation is due chiefly to endogenous choline synthesis, balanced by degradation, whereas the more responsive process of sarcosine formation may be due chiefly to methylation of glycine. Together with available data, these new data on methionine consumption due to sarcosine formation permit calculation of a turnover time for S-adenosylmethionine in human liver (no more than 3.5–7 min), as well as upward revision of previous minimal estimates1 of the rate of methylneogenesis, the number of times that the average homocysteinyl moiety cycles between methionine and homocysteine during its passage through the body, and the partitioning of homocysteine between the remethylation and the transsulfuration pathways.
Article
Only two S-adenosyl-L-methionine synthetase forms exist in rat liver: high-Mr S-adenosyl-L-methionine synthetase and low-Mr S-adenosyl-L-methionine synthetase, which have been purified to apparent homogeneity as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. High-Mr S-adenosyl-L-methionine synthetase had an apparent molecular mass, determined by gel filtration, of 210 kDa and was a tetramer constituted by 48.5-kDa subunits, estimated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The apparent molecular mass of low-Mr S-adenosyl-L-methionine synthetase, as estimated by gel filtration, was 110 kDa and was constituted by two subunits of 47 kDa. An antiserum against low-Mr S-adenosyl-L-methionine synthetase cross-reacted with the two forms. Reverse-phase HPLC runs of tryptic digestions of high-Mr and low-Mr S-adenosyl-L-methionine synthetase showed that the peptide maps of the two forms were very similar, if not identical. High-Mr S-adenosyl-L-methionine synthetase activity was inhibited by S-adenosyl-L-methionine and pyrophosphate. Depending on the dose used, S-adenosyl-L-methionine activated or inhibited low-Mr S-adenosyl-L-methionine synthetase and pyrophosphate had no effect on this form. The two synthetases showed a different specific activity at the physiological concentration of methionine. This report shows that even though the two forms are constructed of the same polypeptide chains, they are regulated in a different manner by methionine and by the products of the reaction.
Article
It is suggested that in man the methyl folate trap is a normal physiological response to impending methyl group deficiency resulting from a very low supply of methionine. This decreases cellular S-adenosyl-methionine (SAM), which puts at risk important methylation reactions, including those required to maintain myelin. In order to protect these methylation reactions, the cell has evolved two mechanisms to maintain supplies of methionine and SAM as a first priority. (a) Decreased SAM causes the folate co-factors to be directed through the cycle involving 5-methyl-tetrahydrofolate (5-methyl-THF) and methionine synthetase and away from the cycles that produce purines and pyrimidines for DNA synthesis. This enhances the remethylation of homocysteine to methionine and SAM. In addition, by restricting DNA biosynthesis and with it cell, division, competition for methionine for protein synthesis is reduced. Thus, whatever methionine is available is conserved for the vital methylation reactions in the nerves, brain, and elsewhere. (b) 5-methyl-THF, the form in which almost all folate is transported in human plasma, must react with intracellular homocysteine before it can be retained by the cell as a polyglutamate. Since homocysteine is derived entirely from methionine, methionine deficiency will cause intracellular folate deficiency, and the rate of mitosis of rapidly dividing cells will be reduced. although these two processes have evolved as a response to methionine deficiency, they also occur in B12 deficiency, which the cell mistakenly interprets as lack of methionine. the resulting response is inappropriate and gives rise to a potentially lethal anaemia. In these circumstances the methylation reactions are also partly protected by the reduced rate of cell division. This explains why administration of folic acid, which induces cell division and use of methionine in protein synthesis, impairs methylation of myelin and precipitates or exacerbates subacute combined degeneration (SCD). During folate deficiency methionine biosynthesis is also diminished. As in methionine deficiency, the body responds to decreasing availability of SAM by diverting folate away from DNA biosynthesis towards the remethylation of homocysteine to methionine and SAM. The selective use pf available folate to conserve methionine, together with the ability of nerve tissue to concentrate folate form the plasma, explains the absence of SCD in folate deficiency.
Article
From the foregoing discussion of the nutritional requirements and some of the metabolic anomalies of the cat, it is clear that the cat is adapted to eating a carnivorous diet. It may, however, have less capability than omnivores and herbivores to adapt to wide ranges in dietary composition. For example, the lack of ability to synthesize sufficient vitamin A from carotene, ornithine from glutamic acid, arachidonate from linoleate, and taurine from cysteine results from a complete deletion or severe limitation of the enzyme or pathway that makes each nutrient. Other nutrient requirements, such as the absolute requirement for niacin and the high protein requirement, appear to result from the high activity of one or more enzymes and the fact that these enzymes are not adaptive in the cat. For example, the cat cannot decrease picolinic carboxylase in order to force tryptophan toward the niacin-synthetic pathway (244) nor can it decrease the urea cycle enzymes when dietary protein is decreased in the diet in order to conserve nitrogen (209). Indeed, the cat appears to have less capability to adapt to most changes in dietary composition because it cannot change the quantities of enzymes involved in the metabolic pathways (209). This evolutionary development has resulted in more stringent nutritional requirements for cats than for omnivores such as the rat, dog, and man. What little evidence exists for other carnivore species leads us to suggest that this pattern may well be common among other strict carnivores. The metabolic differences between the cat and omnivores provide the researcher with a useful animal model for studying the biochemical basis of some nutrient requirements. For example, because there is no significant conversion of linoleate to arachidonate in cat liver (101, 150, 231), the physiological functions of linoleate can be determined independent of it having a role as a precursor of arachidonate (150). This has not been possible with other species. It is anticipated that further studies of the nutrition of the cat will increase our understanding of metabolic adaptation and nutrient functions.
Article
Amino acid concentrations in whole blood, liver, kidney, skeletal muscle, and brain were measured and arteriovenous differences calculated for head, hindlimb, kidney, gut, and liver in control and streptozotocin-diabetic rats. In the control rats, glutamine was released by muscle and utilized by intestine, intestine released citrulline and alanine, liver removed alanine, and the kidneys removed glycine and produced serine. In diabetic rats, the major changes from the pattern of fluxes seen in the normal rat were the release of many amino acids from muscle, with glutamine and alanine predominating, and the uptake of these amino acids by the liver. Glutamine removal by the intestine was suppressed in diabetes, but a large renal uptake of glutamine was evident. Branched-chain amino acids were removed by the diabetic brain, and consequently, brain levels of a number of large neutral amino acids were decreased in diabetes.
Article
The uptake of tyrosine and leucine by brain of control and diabetic rats was examined using the Oldendorf intracarotid injection technique. The brain uptake indexes (BUI) for tyrosine and leucine were identical in diabetic and control rats when the injectate consisted of labeled amino acids in Krebs saline. When the injectate consisted of radioactive amino acids added to plasma from either normal or diabetic rats, there was a decreased BUI for tyrosine from diabetic plasma compared with that from normal plasma. This was evident in both control and diabetic rats. Fractional uptake of leucine was unchanged in all situations. Because leucine level is elevated in plasma of diabetic rats there is an absolute increase in leucine uptake in diabetes. Branched-chain amino acids, added to normal plasma in the concentrations at which they occur in diabetic plasma, inhibited the uptake of tyrosine to the same extent as diabetic plasma did. We conclude that the decreased brain uptake and decreased brain level of tyrosine in diabetes is due to the high circulating levels of branched-chain amino acids and cannot be attributed to intrinsic changes in the blood-brain transporter for large neutral amino acids or to changes in other constituents of plasma.
Article
Arsenic metabolism has typically been studied by administering arsenate or arsenite into animals and humans and then studying the metabolites excreted in the urine. Although such studies have yielded information about the beginning and the end of the metabolic pathways for the metabolism of inorganic arsenic compounds, any statements as to the molecular mechanisms of these reactions have had to be highly speculative. Now that the rabbit and the rhesus monkey liver enzymes that transfer methyl groups from S-adenosylmethionine to arsenite and monomethlyarsonic acid have been purified and the reactions characterized, meaningful investigations of species diversity and polymorphism of these enzymes have become possible. New World animals studied thus far appear to be deficient in or totally lacking these enzymes. Old World animals, with the exception of the chimpanzee, have ample amounts of arsenite and monomethylarsonic acid methyltransferases. A hypothesis that the lack of arsenite methyltransferases may have had an evolutionary advantage for certain species is proposed.
Article
Protein synthesis is initiated universally with the amino acid methionine. In Escherichia coli , studies with anticodon sequence mutants of the initiator methionine tRNA have shown that protein synthesis can be initiated with several other amino acids. In eukaryotic systems, however, a yeast initiator tRNA aminoacylated with isoleucine was found to be inactive in initiation in mammalian cell extracts. This finding raised the question of whether methionine is the only amino acid capable of initiation of protein synthesis in eukaryotes. In this work, we studied the activities, in initiation, of four different anticodon sequence mutants of human initiator tRNA in mammalian COS1 cells, using reporter genes carrying mutations in the initiation codon that are complementary to the tRNA anticodons. The mutant tRNAs used are aminoacylated with glutamine, methionine, and valine. Our results show that in the presence of the corresponding mutant initiator tRNAs, AGG and GUC can initiate protein synthesis in COS1 cells with methionine and valine, respectively. CAG initiates protein synthesis with glutamine but extremely poorly, whereas UAG could not be used to initiate protein synthesis with glutamine. We discuss the potential applications of the mutant initiator tRNA-dependent initiation of protein synthesis with codons other than AUG for studying the many interesting aspects of protein synthesis initiation in mammalian cells.
Article
Homocysteine is a key junction metabolite in methionine metabolism. It suffers two major metabolic fates: transmethylation catalyzed by methionine synthase or betaine homocysteine methyl transferase and transsulfuration catalyzed by cystathionine beta-synthase leading to cystathionine. The latter is subsequently converted to cysteine, a precursor of glutathione. Studies with purified mammalian methionine synthase and cystathionine beta-synthase have revealed the oxidative sensitivity of both junction enzymes, suggesting the hypothesis that redox regulation of this pathway may be physiologically significant. This hypothesis has been tested in a human hepatoma cell line in culture in which the flux of homocysteine through transsulfuration under normoxic and oxidative conditions has been examined. Addition of 100 microM H(2)O(2) or tertiary butyl hydroperoxide increased cystathionine production 1.6- and 2.1-fold from 82 +/- 7 micromol h(-)(1) (L of cells)(-)(1) to 136 +/- 15 and 172 +/- 23 micromol h(-)(1) (L of cells)(-)(1), respectively. The increase in homocysteine flux through the transsulfuration pathway exhibited a linear dose dependence on the concentrations of both oxidants (50-200 microM H(2)O(2) and 10-200 microM tertiary butyl hydroperoxide). Furthermore, our results reveal that approximately half of the intracellular glutathione pool in human liver cells is derived from homocysteine via the transsulfuration pathway. The redox sensitivity of the transsulfuration pathway can be rationalized as an autocorrective response that leads to an increased level of glutathione synthesis in cells challenged by oxidative stress. In summary, this study demonstrates the importance of the homocysteine-dependent transsulfuration pathway in the maintenance of the intracellular glutathione pool, and the regulation of this pathway under oxidative stress conditions. Aberrations in this pathway could compromise the redox buffering capacity of cells, which may in turn be related to the pathophysiology of the different homocysteine-related diseases.
Article
Methionine metabolism forms homocysteine via transmethylation. Homocysteine is either 1) condensed to form cystathionine, which is cleaved to form cysteine, or 2) remethylated back to methionine. Measuring this cycle with the use of isotopically labeled methionine tracers is problematic, because the tracer is infused into and measured from blood, whereas methionine metabolism occurs inside cells. Because plasma homocysteine and cystathionine arise from intracellular metabolism of methionine, plasma homocysteine and cystathionine enrichments can be used to define intracellular methionine enrichment during an infusion of labeled methionine. Eight healthy, postabsorptive volunteers were given a primed continuous infusion of [1-13C]methionine and [methyl-2H(3)]methionine for 8 h. Enrichments in plasma methionine, [13C]homocysteine and [13C]cystathionine were measured. In contrast to plasma methionine enrichments, the plasma [13C]homocysteine and [13C]cystathionine enrichments rose to plateau slowly (rate constant: 0.40 +/- 0.03 and 0.49 +/- 0.09 h(-1), respectively). The enrichment ratios of plasma [13C]homocysteine to [13C]methionine and [13C]cystathionine to [13C]methionine were 58 +/- 3 and 54 +/- 3%, respectively, demonstrating a large intracellular/extracellular partitioning of methionine. These values were used to correct methionine kinetics. The corrections increase previously reported rates of methionine kinetics by approximately 40%.
Article
We showed previously that 64% of the total dietary sulfur amino acid (SAA) requirement could be supported by dietary cysteine (Cys). However, the observation of such a sparing effect may be affected by the dietary intakes of SAA provided. The aim of this study was to compare methionine (Met) metabolism and transsulfuration (TS) in five healthy men fed three different diets (in random order) for 3 d each, with varying combinations of Met and Cys: 24 mg Met/(kg. d) and no Cys (diet A); 13 mg Met/(kg. d) and 11 mg Cys/(kg. d) (diet B); and 5 mg Met/(kg. d) and 19 mg Cys/(kg. d) (diet C). On d 3, Met kinetics and TS were assessed using orally administered L-[1-(13)C, methyl-(2)H(3)]methionine. Met demethylation (transmethylation, TM) significantly decreased as the dietary Met to Cys ratio decreased. Met TS was significantly lower during diets B [2.8 +/- 0.4 micro mol/(kg. h)] and C [1.5 +/- 0.5 micro mol/(kg. h)] than during diet A [7.8 +/- 2.9 micro mol/(kg. h)] (P < 0.05). The results of the present study indicate that when the ratio of Met to Cys fed is typical of that found in major food proteins and total SAA are sufficient to meet requirements, TS is significantly reduced compared with the case in which SAA needs are supplied by Met alone. We conclude that Cys sparing occurs through an increase in the fraction of the homocysteine pool destined for RM relative to TS (RM:TS).
Article
In certain tissues, glutathione biosynthesis is connected to methionine metabolism via the trans-sulfuration pathway. The latter condenses homocysteine and serine to cystathionine in a reaction catalyzed by cystathionine beta-synthase followed by cleavage of cystathionine to cysteine and alpha-ketoglutarate by gamma-cystathionase. Cysteine is the limiting amino acid in glutathione biosynthesis, and studies in our laboratory have shown that approximately 50% of the cysteine in glutathione is derived from homocysteine in human liver cells. In this study, we have examined the effect of pro- and antioxidants on the flux of homocysteine through the trans-sulfuration pathway in the human hepatoma cell line, HepG2. Our studies reveal that pyrrolidine dithiocarbamate and butylated hydroxyanisole enhance the flux of homocysteine through the trans-sulfuration pathway as has been observed previously with the pro-oxidants, H(2)O(2) and tertiary butyl hydroperoxide. In contrast, antioxidants such as catalase, superoxide dismutase and a water-soluble derivative of vitamin E elicit the opposite effect and result in diminished flux of homocysteine through the trans-sulfuration pathway. These studies provide the first evidence for the reciprocal sensitivity of the trans-sulfuration pathway to pro- and antioxidants, and demonstrate that the upstream half of the glutathione biosynthetic pathway (i.e. leading to cysteine biosynthesis) is redox sensitive as is the regulation of the well-studied enzymes in the downstream half (leading from cysteine to glutathione), namely, gamma-glutamyl-cysteine ligase and glutathione synthetase.
Article
Neurotransmitter receptors are central to communication at synapses. Many components of the machinery for neurotransmission are present prior to synapse formation, suggesting a developmental role. Here, evidence is presented that signaling through glycine receptor alpha2 (GlyRalpha2) and GABA(A) receptors plays a role in photoreceptor development in the vertebrate retina. The signaling is likely mediated by taurine, which is present at high levels throughout the developing central nervous system (CNS). Taurine potentiates the production of rod photoreceptors, and this induction is inhibited by strychnine, an antagonist of glycine receptors, and bicuculline, an antagonist of GABA receptors. Gain-of-function experiments showed that signaling through GlyRalpha2 induced exit from mitosis and an increase in rod photoreceptors. Furthermore, targeted knockdown of GlyRalpha2 decreased the number of photoreceptors while increasing the number of other retinal cell types. These data support a previously undescribed role for these ligand-gated ion channels during the early stages of CNS development.
Article
S-adenosylmethionine (SAM or AdoMet) is a biological sulfonium compound known as the major biological methyl donor in reactions catalyzed by methyltransferases. SAM is also used as a source of methylene groups (in the synthesis of cyclopropyl fatty acids), amino groups (in the synthesis of 7,8-diaminoperlagonic acid, a precursor of biotin), ribosyl groups (in the synthesis of epoxyqueuosine, a modified nucleoside in tRNAs) and aminopropyl groups (in the synthesis of ethylene and polyamines). Even though the mechanism of most of these reactions has not been extensively characterized, it is likely that the chemistry at work is mainly driven by the electrophilic character of the carbon centers that are adjacent to the positively charged sulfur atom of SAM. In addition, SAM, upon one-electron reduction, is a source of 5'-deoxyadenosyl radicals, which initiate many metabolic reactions and biosynthetic pathways by hydrogen-atom abstraction. SAM presents a unique situation in which all constituent parts have a chemical use.
Article
Cystathionine beta-synthase in mammals lies at a pivotal crossroad in methionine metabolism directing flux toward cysteine synthesis and catabolism. The enzyme exhibits a modular organization and complex regulation. It catalyzes the beta-replacement of the hydroxyl group of serine with the thiolate of homocysteine and is unique in being the only known pyridoxal phosphate-dependent enzyme that also contains heme b as a cofactor. The heme functions as a sensor and modulates enzyme activity in response to redox change and to CO binding. Mutations in this enzyme are the single most common cause of hereditary hyperhomocysteinemia. Elucidation of the crystal structure of a truncated and highly active form of the human enzyme containing the heme- and pyridoxal phosphate binding domains has afforded a structural perspective on mechanistic and mutation analysis studies. The C-terminal regulatory domain containing two CBS motifs exerts intrasteric regulation and binds the allosteric activator, S-adenosylmethionine. Studies with mammalian cells in culture as well as with animal models have unraveled multiple layers of regulation of cystathionine beta-synthase in response to redox perturbations and reveal the important role of this enzyme in glutathione-dependent redox homestasis. This review discusses the recent advances in our understanding of the structure, mechanism, and regulation of cystathionine beta-synthase from the perspective of its physiological function, focusing on the clinically relevant human enzyme.
Article
Oxidative damage to proteins is considered to be one of the major causes of aging and age-related diseases, and thus mechanisms have evolved to prevent or reverse these modifications. Methionine is one of the major targets of reactive oxygen species (ROS), where it is oxidized to methionine sulfoxide (MetO). Recently, evidence has accumulated suggesting that methionine (Met) oxidation may play an important role in the development and progression of neurodegenerative diseases like Alzheimer's and Parkinson's diseases. Oxidative alteration of Met to Met(O) is reversed by the methionine sulfoxide reductases (consisting of MsrA enzymes that reduce S-MetO and MsrB enzymes that reduce R-MetO, respectively). A major biological role of the Msr system is suggested by the fact that the MsrA null mouse (MT) exhibits a neurological disorder in the form of ataxia ("tip toe walking"), is more sensitive to oxidative stress, and has a shorter life span (by approximately 40%) than wild-type (WT) mice. By their action, the Msr enzymes can regulate protein function, be involved in signal-transduction pathways, and prevent cellular accumulation of faulty proteins. Malfunction of the Msr system can lead to cellular changes resulting in compromised antioxidant defense, enhanced age-associated diseases involving neurodegeneration, and shorter life span. In this review, the function and possible roles of the Msr system in prokaryotes and eukaryotes, in general, and in neurodegenerative diseases, in particular, will be discussed.
Article
S-Adenosylmethionine (AdoMet) is the major biological methyl donor. AdoMet's methyl group arises both from the diet (eg, methionine, choline, and betaine) and from de novo synthesis by the process of methylneogenesis. At least 50 AdoMet-dependent methylation reactions have been identified in mammals, and genomic analyses suggest that the final number will be much higher. Such methylation reactions play major roles in biosynthesis, regulation, and detoxification. Creatine synthesis is thought to account for the use of >70% of AdoMet-derived methyl groups in humans. This is not consistent with recent studies in mice, in which the phosphatidylethanolamine methyltransferase gene was deleted (PEMT-/-). Loss of this hepatic enzyme resulted in a 50% decrease in plasma homocysteine, which suggests that it accounts for a major component of whole-body AdoMet utilization. A reexamination of human creatine metabolism showed that dietary creatine can account for as much as 50% of daily creatine requirements in nonvegetarians and, therefore, that estimates of creatine synthesis need to be reduced. We suggest that creatine synthesis is responsible for a smaller proportion of AdoMet-derived methyl groups than has been suggested and that phosphatidylcholine synthesis via phosphatidylethanolamine methyltransferase is a major consumer of these methyl groups.
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