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Glycine formation from betaine (trimethylglycine) BHMT betaine homocysteine methyltransferase, DMGD dimethylglycine dehydrogenase, SD sarcosine dehydrogenase

Glycine formation from betaine (trimethylglycine) BHMT betaine homocysteine methyltransferase, DMGD dimethylglycine dehydrogenase, SD sarcosine dehydrogenase

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Plasma glycine level is low in patients with obesity or diabetes and the improvement of insulin resistance increases plasma glycine concentration. In prospective studies, hypoglycinemia at baseline predicts the risk of developing type 2 diabetes and higher serum glycine level is associated with decreased risk of incident type 2 diabetes. Consistent...

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... Branched-chain amino acids (BCAAs), phenylalanine, and tyrosine are among the commonly reported amino acids with elevated plasma concentrations in individuals with obesity (1). Glycine, by contrast, has a lower plasma concentration in patients with obesity compared to those with a healthy weight (2) (3,4). Higher plasma concentration of BCAAs in obesity has been attributed to either accelerated flux from protein breakdown (5,6) or dysregulated BCAA clearance (7)(8)(9). ...
... At the same time, glycine is required in large quantities by the human body for the biosynthesis of physiologically important biomolecules, maintenance of oxidative and detoxification defenses, and growth and development (11,12). Since obesity is a state of heightened metabolic demand, plasma glycine concentration can be low due to an increase in glycine catabolism or the diversion of glycine to utilization pathways (3,4). However, the underlying kinetic changes in the metabolic pathways responsible for obesityassociated hypoglycinemia have not been well studied (3,4). ...
... Since obesity is a state of heightened metabolic demand, plasma glycine concentration can be low due to an increase in glycine catabolism or the diversion of glycine to utilization pathways (3,4). However, the underlying kinetic changes in the metabolic pathways responsible for obesityassociated hypoglycinemia have not been well studied (3,4). ...
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Background Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance. Objective Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m ² ) to those with healthy weight (BMI < 25 kg/m ² ), and 2) Comparing glycine kinetic changes in participants with morbid obesity after bariatric surgery. Methods [1,2- ¹³ C 2 ] glycine, [2,3,3- ² H 3 ] serine, and [ ² H 5 ] phenylalanine were infused to compare the glycine kinetic parameters between 21 participants with morbid obesity and 21 controls with healthy weight. Participants with morbid obesity then underwent bariatric surgery and 17 were re-studied 6 months later. Data were analyzed by non-parametric methods and presented as median (interquartile range). Results Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced de novo glycine synthesis rate at 86.2 (64.5-111) vs.124 (103-159) µmol·kg LBM ⁻¹ ·h ¹ , p < 0.001. Following surgery, body weight and insulin resistance decreased and this was accompanied by significant increases in plasma glycine concentration to 210 (191-243) µmol/L as well as the de novo glycine synthesis rate to 127 (98.3-133) µmol·kg LBM ⁻¹ ·h ⁻¹ , p < 0.001 vs. baseline. Conclusion Hypoglycinemia in participants with morbid obesity was associated with impaired de novo glycine synthesis. The increase in plasma glycine concentration and de novo glycine synthesis plus the marked improvement in insulin resistance after bariatric surgery suggest that hypoglycinemia may be secondary to impaired glycine synthesis because of obesity-induced insulin resistance. Clinical Trial Registration [ https://tinyurl.com/6wfj7yss ], identifier [NCT04660513].
... Glycine plays vital roles in organic metab-olism and acts as a precursor of serine, purines, creatine, sarcosine, glutathione, and collagen. As required in stabilizing the triple helix of collagen, glycine has a critical role in maintaining collagen structure [41]. Glycine could limit the acyl-CoA excretion in the form of acyl-glycine in urine [37]. ...
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Diabetes is a worldwide metabolic disease with rapid growing incidence, characterized by hyperglycemia. Diabetic kidney disease (DKD), the leading cause of chronic kidney disease (CKD), has a high morbidity according to the constantly increasing diabetic patients and always develops irreversible deterioration of renal function. Though different in pathogenesis, clinical manifestations, and therapies, both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) can evolve into DKD. Since amino acids are both biomarkers and causal agents, rarely report has been made about its metabolism which lies in T1DM- and T2DM-related kidney disease. This study was designed to investigate artemether in adjusting renal amino acid metabolism in T1DM and T2DM mice. Artemether was applied as treatment in streptozotocin (STZ) induced T1DM mice and db/db T2DM mice, respectively. Artemether-treated mice showed lower FBG and HbA1c and reduced urinary albumin excretion, as well as urinary NAG. Both types of diabetic mice showed enlarged kidneys, as confirmed by increased kidney weight and the ratio of kidney weight to body weight. Artemether normalized kidney size and thus attenuated renal hypertrophy. Kidney tissue UPLC-MS analysis showed that branched-chain amino acids (BCAAs) and citrulline were upregulated in diabetic mice without treatment and downregulated after being treated with artemether. Expressions of glutamine, glutamic acid, aspartic acid, ornithine, glycine, histidine, phenylalanine and threonine were decreased in both types of diabetic mice whereas they increased after artemether treatment. The study demonstrates the initial evidence that artemether exerted renal protection in DKD by modulating amino acid metabolism.
... Homocysteine interferes with the phosphorylation of insulin receptors to attenuate insulin signal transduction (36). Contrary to other serum amino acids, serum glycine concentration can reduce the accumulation of free fatty acids in the serum and is associated with a lower risk of type 2 diabetes (37). Therefore, this study suggested that the Low-GID reduced insulin resistance based on serum amino acids and their derivative concentrations compared to CD. ...
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... The lower glycine levels in circulation are related to obesity, diabetes and nonalcoholic fatty liver disease (NAFLD), and GlyR expression and glycine-induced currents on b cells of T2D patients is also reduced (52,53). Supplementation with glycine can alleviate oxidative stress, lower blood pressure, and reduce risks for T2D (54). ...
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... Circulating levels of L-tryptophan have been linked to increased insulin resistance and risk of diabetes (33). Conversely, L-serine and glycine are associated with improved insulin sensitivity (34,35). There was also depletion of multiple pathways and enzymes related to galacturonate and glucuronate catabolism. ...
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... Similarly, there was a negative correlation between HOMA-IR and glycine levels. These data agreed with previous findings, indicating decreased glycine levels as characteristic of insulin resistance [60]. The alterations at multiple levels of glycine and serine metabolism were shown to be important in obesity and T2D [61]. ...
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Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were collected. The concentration of 23 amino acids and 10 biogenic amines in serum and tear samples was analyzed. Statistical analysis and Pearson correlation analysis along with network analysis were carried out. Compared to controls, changes in the level of 6 analytes in the obese group and of 10 analytes in the T2D group were statistically significant. For obesity, the energy generation, while for T2D, the involvement of NO synthesis and its relation to insulin signaling and inflammation, were characteristic. We found that BCAA and glutamine metabolism, urea cycle, and beta-oxidation make up crucial parts of the metabolic changes in T2D. According to our data, the retromer-mediated retrograde transport, the ethanolamine metabolism, and, consequently, the endocannabinoid signaling and phospholipid metabolism were characteristic of both conditions and can be relevant pathways to understanding and treating insulin resistance. By providing potential therapeutic targets and new starting points for mechanistic studies, our results emphasize the importance of complex data analysis procedures to better understand the pathomechanism of obesity and diabetes.
... Additionally, a few studies examining the roles of lipid metabolism, including carnitines, acylcarnitines, and lysophosphatidylcholine (LPC) species, have shown the associations with insulin resistance or inflammation [13][14][15]. These metabolites are also involved in mitochondrial function and redox homeostasis, which may contribute to the mechanisms of frailty or sarcopenia [16][17][18]. However, relatively less research has been carried out in the area of relationship between these lipid metabolites with sarcopenia and its components.. ...
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Background Metabolic profiling may provide insights into the pathogenesis and identification of sarcopenia; however, data on the metabolic basis of sarcopenia and muscle-related parameters among older adults remain incompletely understood. This study aimed to identify the associations of metabolites with sarcopenia and its components, and to explore metabolic perturbations in older men, who have a higher prevalence of sarcopenia than women. Methods We simultaneously measured the concentrations of amino acids, carnitine, acylcarnitines, and lysophosphatidylcholines (LPCs) in serum samples from a cross-sectional study of 246 Chinese older men, using targeted metabolomics. Sarcopenia and its components, including skeletal muscle index (SMI), 6-m gait speed, and handgrip strength were assessed according to the algorithm of the Asian Working Group for Sarcopenia criteria. Associations were determined by univariate and multivariate analyses. Results Sixty-five (26.4%) older men with sarcopenia and 181 (73.6%) without sarcopenia were included in the study. The level of isovalerylcarnitine (C5) was associated with the presence of sarcopenia and SMI. Regarding the overlapped metabolites for muscle parameters, among ten metabolites associated with muscle mass, six metabolites including leucine, octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14), and LPC18:2 were associated with handgrip strength, and three of which (C12, C14, and LPC18:2) were also associated with gait speed. Specifically, tryptophan was positively associated and glycine was negatively associated with handgrip strength, while glutamate was positively correlated with gait speed. Isoleucine, branched chain amino acids, and LPC16:0 were positively associated with SMI. Moreover, the levels of LPC 16:0,18:2 and 18:0 contributed significantly to the model discriminating between older men with and without sarcopenia, whereas there were no significant associations for other amino acids, acylcarnitines, and LPC lipids. Conclusions These results showed that specific and overlapped metabolites are associated with sarcopenic parameters in older men. This study highlights the potential roles of acylcarnitines and LPCs in sarcopenia and its components, which may provide valuable information regarding the pathogenesis and management of sarcopenia.
... In addition, glycine is a non-essential amino acid, and is known to be low in patients with diabetes. A previous study showed that higher glycine level is associated with decreased risk of type 2 diabetes [62]. In this study, the changes in glycine levels in the exercise groups (MES and HES) after SD significantly increased compared to rest after SD. ...
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The purpose of this study is to determine the difference in sleep-related factors and metabolites between normal sleep (NS) and sleep deficiency (SD) and to analyze the variations in metabolites according to the intensity of aerobic exercise under SD conditions. This study was conducted on 32 healthy male university students. Participants experienced both NS (8 h of sleep per night for 3 consecutive days) and SD (4 h of sleep per night for 3 consecutive days). After the SD period, the participants underwent treatment for 30 min by the assigned group [sleep supplement after SD (SSD), low-intensity aerobic exercise after SD (LES), moderate-intensity aerobic exercise after SD (MES), high-intensity aerobic exercise after SD (HES)]. For analysis, sleep-related factors were measured, and metabolites were analyzed by untargeted metabolite analysis using gas chromatography-time-of-flight mass spectrometry. As a result, SD showed that total sleep time (TST), duration of rapid eye movement (REM), duration of light sleep, and duration of deep sleep were significantly decreased compared to NS, whereas the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and visual analogue scale (VAS) were significantly increased compared to NS. The difference in metabolites between NS and SD showed that there were significant changes in the seven metabolites. There were 18 metabolites that changed according to the treatment groups in SD conditions. In summary, SD can exacerbate sleep quality, induce daytime sleepiness, increase fatigue, and increase metabolites that cause insulin resistance. Aerobic exercise under SD conditions can reduce metabolites that induce insulin resistance and increase the metabolites that help relieve depression caused by SD. However, HES has a negative effect, which increases fatigue, whereas LES has no negative effect. Thus, this study suggests that LES is the most appropriate exercise method under SD conditions.
... C5 was also moderately associated with LPC16:0 and LPC18:2, and the reduction in C5 and LPCs levels may be owing to impaired mitochondrial oxidative capacity (62). The accumulation of non-oxidized fatty acids promotes their conjugation with glycine and carnitine and alternate ways of oxidation (63). The underlying mechanism of the correlations among other metabolites are still unclear, and future research is needed in metabolic pathway analysis. ...
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Background As an age-related syndrome, frailty may play a central role in poor health among older adults. Sarcopenia overlaps with the physical domain of frailty, and most existing studies have analyzed the associated factors of frailty and sarcopenia as an isolated state. Perturbations in metabolism may play an important role in the presence of frailty or sarcopenia; however, the metabolites associated with frailty, especially overlapping with sarcopenia remain unclear. In this study, we aimed to explore whether amino acids, carnitines, acylcarnitines and lysophosphatidylcholines, as specific panels, are significantly correlated with frailty, especially overlapping with sarcopenia, to gain insight into potential biomarkers and possible biological mechanisms and to facilitate their management. Methods We applied a targeted high-performance liquid chromatography-tandem mass spectrometry approach in serum samples from 246 Chinese older men (age 79.2 ± 7.8 years) with frailty ( n = 150), non-frailty ( n = 96), frailty and sarcopenia ( n = 52), non-frail and non-sarcopenic control ( n = 85). Frailty was evaluated using Freid phenotype criteria, sarcopenia was defined by diagnostic algorithm of Asian Working Group on Sarcopenia, and the participants were diagnosed as frailty and sarcopenia when they met the evaluation criteria of both frailty and sarcopenia. A panel of 29 metabolomic profiles was assayed and included different classes of amino acids, carnitines, acylcarnitines, and lysophosphatidylcholines (LPCs). Multivariate logistic regression was used to screen the metabolic factors contributing to frailty status, and orthogonal partial least squares discriminant analysis was used to explore important factors and distinguish different groups. Results In older men demonstrating the frail phenotype, amino acid perturbations included lower tryptophan and higher glycine levels. With regard to lipid metabolism, the frailty phenotype was characterized by lower concentrations of isovalerylcarnitine (C5), LPC16:0 and LPC18:2, while higher levels of octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14). After adjusting for several clinical confounders, tryptophan, LPC18:2, LPC 16:0 and C5 were negatively correlated with frailty, and C8 and C12 were positively related to frailty. We preliminarily identified metabolic profiles (LPC16:0, LPC18:2, glycine and tryptophan) that may distinguish older men with frailty from those without frailty. Importantly, a set of serum amino acids and LPCs (LPC16:0, LPC18:2, and tryptophan) was characterized in the metabotype of older adults with an overlap of frailty and sarcopenia. The metabolites that were most discriminating of frailty status implied that the underlying mechanism might be involved in antioxidation and mitochondrial dysfunction. Conclusions These present metabolic analyses may provide valuable information on the potential biomarkers and possible biological mechanisms of frailty, and overlapping sarcopenia. The findings obtained may offer insight into their management in older adults.
... Diet and endogenous synthesis (in the liver and kidneys) are two sources of glycine intake in humans. Glycine can be generated from choline, glycine oxalate, betaine (trimethylglycine), glucose (via serine), during the endogenous synthesis of L-carnitine and likely from threonine [2]. ...
... Glycine is utilized in some metabolic pathways including degradation to carbon dioxide and ammonium, producing serine via the reversible reaction catalyzed by serine hydroxymethyltransferase, methylation to generate N-methylglycine (sarcosine) and conjugation by acyl groups derived from acyl-CoA esters to generate acyl-glycine derivatives. Glycine is required to synthesize heme group, purines, creatine, collagen and glutathione [2]. ...
... Glycine moieties are critical to stabilizing the three-chain superhelix. Therefore, the healthy collagen structure in the human body needs glycine [2]. ...
Article
PurposeGlycine is the simplest and major amino acid in humans. It is mainly generated in the liver and kidney and is used to produce collagen, creatine, glucose and purine. It is also involved in immune function, anti-inflammatory processes and anti-oxidation reactions. Here, we reviewed the current evidence supporting the role of glycine in the development and treatment of metabolic syndrome components.Methods We searched Scopus, PubMed and EMBASE databases for papers concerning glycine and metabolic syndrome.ResultsAvailable evidence shows that the amount of glycine synthesized in vivo is insufficient to meet metabolic demands in these species. Plasma glycine levels are lower in subjects with metabolic syndrome than in healthy individuals. Interventions such as lifestyle modification, exercise, weight loss, or drugs that improve manifestations of metabolic syndrome remarkably increase circulating glycine concentrations.Conclusion Glycine supplementation improves various components of metabolic syndrome including diabetes, obesity, hyperlipidemia and hypertension. In the future, the use of glycine may have a significant clinical impact on the treatment of patients with metabolic syndrome.