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Biotin and biotinidase deficiency
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Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role in transcriptional repression of genes and genome stability. Biotin deficiency may be caused by insufficient dietary uptake of biotin, drug-vitamin interactions and, perhaps, by increased biotin catabolism during pregnancy and in smokers. Biotin deficiency can also be precipitated by decreased activities of the following proteins that play critical roles in biotin homeostasis: the vitamin transporters sodium-dependent multivitamin transporter and monocarboxylate transporter 1, which mediate biotin transport in the intestine, liver and peripheral tissues, and renal reabsorption; holocarboxylase synthetase, which mediates the binding of biotin to carboxylases and histones; and biotinidase, which plays a central role in the intestinal absorption of biotin, the transport of biotin in plasma and the regulation of histone biotinylation. Symptoms of biotin deficiency include seizures, hypotonia, ataxia, dermatitis, hair loss, mental retardation, ketolactic acidosis, organic aciduria and also fetal malformations. This review focuses on the deficiencies of both biotin and biotinidase, and the medical management of such cases.
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... Recent research has shown novel roles for vitamin B7 in cell signalling and epigenetic control and it must bind to specific lysine residues. Human colonic epithelium uptake of biotin is a carrier-mediated mechanism (Agrawal et al., 2016;Zempleni et al., 2008). Three important carboxylation events, such as the transformation of pyruvate into oxalacetate, acetyl-CoA into malonyl-CoA, and propionyl-CoA into methyl malonyl-CoA, all require vitamin B7 as a cofactor. ...
Vitamins are essential for a healthy life. Compared to other nutrients, the body needs them in very small amounts. B vitamins, often known as the vitamin B complex, are a class of water-soluble vitamins with key functions in cellular metabolism. Thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), folate (vitamin B9), often known as folic acid, and cobalamin (vitamin B12) are the eight distinct vitamins that collectively constitute the vitamin B complex. The body's energy levels, cognitive activity, and cell metabolism are all directly impacted by B vitamins. Four main factors contribute to vitamin B deficiency: an unbalanced diet, excessive alcohol intake, different drugs, and disorders that induce gut malabsorption. If these B vitamin deficiencies are left untreated, they can eventually cause symptoms such as peripheral neuropathy, heart attacks, strokes etc. B vitamins are present in natural, whole foods. Compared to their unprocessed counterparts, white flour and other processed carbohydrates like sugar often contain fewer B vitamins. Excellent sources of vitamins Bs comprise legumes (beans or pulses), potatoes, bananas, whole grains, tempeh, chilli peppers, brewer's yeast, nutritional yeast, and molasses. This paper provides an in-depth summary of the most popular types of vitamin B, emphasizing why the body needs them, the symptoms of a deficiency, and what diet or foods are rich in them.
... Биотин является коферментом карбоксилаз, участвующих в переработке аминокислот, жирных кислот, а также в глюконеогенезе. Биотинилирование гистоновых белков в ядерном хроматине играет важную роль в поддержке стабильности ДНК и в экспрессии генов [34,35]. ...
We present the results of a systemic biological analysis of human proteome proteins, biological functions of which are somehow related to the metabolism of B group vitamins and the molecular implementation of nociceptive processes. Among 983 proteins involved in the homeostasis of B vitamins, 21 proteins were involved in the molecular mechanisms of nociception, 91 proteins were involved in the regulation of inflammation processes, and 17 proteins were involved in the neuroprotective and neurotrophic effects of B vitamins. All these groups of proteins are important for the treatment of neuropathic pain associated with the degeneration of nervous tissue.
... A review by Kriteeka Saini et al. [62] investigated the effect of vitamin D supplementation on hair growth and found that vitamin D plays a role in various signaling pathways for hair follicle growth and differentiation. Other nutritional supplements, such as biotin, caffeine, melatonin, and zinc, have been proposed as potential therapies for hair loss, but the exact therapeutic mechanisms remain unclear [63][64][65][66]. While nutritional supplements are often used off-label or as adjuvant therapy in treating FPHL, a large body of evidence is s\ll needed to support their efficacy. ...
Pattern hair loss can occur in both men and women, and the underlying molecular mechanisms have been continuously studied in recent years. Male androgenetic alopecia (M-AGA), also termed male pattern hair loss, is the most common type of hair loss in men. M-AGA is considered an androgen-dependent trait with a background of genetic predisposition. The interplay between genetic and non-genetic factors leads to the phenotype of follicular miniaturization. Although this similar pattern of phenotypic miniaturization can also be found in female pattern hair loss (FPHL), the corresponding genetic factors in M-AGA do not account for the phenotype in FPHL, indicating that there are different genes contributing to FPHL. Therefore, the role of genetic factors in FPHL is still uncertain. Understanding the genetic mechanism that causes FPHL is crucial for the future development of personalized treatment strategies. This review aims to highlight the differences in the ethnic prevalence and genetic background of FPHL, as well as the current genetic research progress in nutrition, Wnt signaling, and sex hormones related to FPHL.
... De honden wogen 6 tot 10,8 kg zodat de gemiddelde dosering ongeveer 1,19 (10/8,4) Noot 20. Het eiwit biotinidase fungeert als transportmiddel voor biotine binnen cellen (41). Bij afwezigheid van biotinidase, veroorzaakt door een genmutatie, ontstaat biotinedeficiëntie. ...
Biotine voor hond en kat Biotine (vitamine B7) is een wateroplosbare, essentiële stof voor het metabolisme van hond en kat. Tekort in het lichaam leidt tot huidaandoeningen. Voor de kat is een voedernorm gesteld, maar niet voor de hond. Aannemelijkerwijs wordt bij beiden de basisbehoefte doorgaans gedekt door microbieel biotine in de darm. Bij de ontdekking van biotine, alsook bij de daaropvolgende, experimenteel geïnduceerde biotinedeficiëntie, speelde rauw ei-eiwit in de voeding een hoofdrol. Dat doet het nog steeds in relatie tot de biotinenormen. Ei-eiwit bevat avidine, een glycoproteïne dat biotine in de darminhoud stevig bindt en onbeschikbaar maakt voor absorptie (Noot 1). Avidine is rijk aan het aminozuur tryptofaan en aan de suiker mannose (1, 2). Intact avidine bindt biotine middels hydrofiele en hydrofobe interacties (3). Eiwitverteringsenzymen kunnen biotine niet vrijmaken uit het avidine-biotine complex (4). Na 15 minuten bij 100 o C was avidine geïnactiveerd, maar het avidine-biotine complex was nog intact (5). Verhitting van rauw ei-eiwit elimineert niet alleen het biotine-bindend vermogen (Noot 2), maar ook de anti-trypsine aktiviteit, waardoor de verteerbaarheid ervan aanzienlijk toeneemt (Noot 3). Ontdekking Boas publiceerde in 1927 dat jonge ratten ziek werden op een voeder met 21% ei-eiwit (in de droge stof), dat bij 37 o C luchtgedroogd was (6, Noot 4). Na drie weken verloren de ratten gewicht en toonden vervolgens een exceemachtige huidontsteking, haaruitval en spastische bewegingen, gevolgd door de dood. De ratten groeiden en bleven gezond wanneer het voeder gekookt ei-eiwit bevatte (Noot 5). In 1939 liet György zien dat een fractie uit gist en lever, genaamd vitamine H, bovengenoemde symptomen genas bij ratten die een voeder met onverhit ei-eiwit kregen (7). Later bleek vitamine H identiek aan biotine, een eerder geïsoleerde groeifactor voor gist (8). H staat voor Haut. De naam biotine is afgeleid van "bios" (leven in het Grieks) en het achtervoegsel "ine", dat in veel chemische namen voorkomt (9, Noot 6). Structuur, functie, voorziening De structuur van biotine werd in 1942 bekend (10). Biotine (C10H16N2O3S) bestaat uit twee gefuseerde ringen, die twee koolstofatomen delen: een 5-ring met 4 koolstofatomen en een zwavelatoom, en een 5-ring met twee koolstof-en twee stikstofatomen, die tussenin een koolstofatoom met ketogroep hebben. De ring met zwavelatoom heeft valeriaanzuur als zijketen. Biotine is een co-factor voor carboxylases, enzymen die kooldioxyde overdragen op hun substraten. Als essentieel onderdeel van drie enzymsystemen, acetyl-CoA-, propionyl-CoA-en pyruvaat-carboxylase, is biotine vereist voor de vetzuursynthese, afbraak van een drietal aminozuren en de synthese van glucose uit melkzuur.
Objective. Increase the effectiveness of complex therapy for patients with telogen alopecia with simultaneous use of the drug «Volvit tablets» (biotin 5 mg) inside and «Volvit intensive care shampoo» with biotin externally. Materials and methods. Patients with telogen alopecia, aged 22 to 40 years, who had complaints and a history of the disease (time of onset of increased hair loss, connection of baldness with stress, medication, viral infection, etc.) were under observation. The main diagnostic measures included: pull test, dermatoscopy, trichoscopy, trichogram, laboratory tests (general blood test, general urine test, biochemical blood test; basic trace elements and vitamins, thyroid gland research), scalp biopsy indicated. Consultations with an endocrinologist, psychotherapist, hematologist and other specialists were scheduled. Results and discussion. On the basis of the analysis of literary sources and own clinical and laboratory studies, a complex therapy of diffuse telogen alopecia was developed with the simultaneous appointment of the drug «Volvit tablets» (biotin 5 mg) and «Volvit intensive care shampoo» with biotin, which has a dual effect (treatment from the inside and cosmetic care behind the hair and scalp from the outside). The diagnosis of diffuse telogen alopecia was established on the basis of the clinical picture of the disease and laboratory diagnostic data. Clinical symptoms in patients with telogen alopecia are manifested by uniform, intense hair loss over the entire head, which is noticed after washing the head and combing, when a lot of hair that has fallen out remains. After examining the patient, an individual treatment plan was drawn up, taking into account the identified factors of the disease and accompanying pathology. One of the most common causes of hair loss is an insufficient amount of biotin in the body, and the causes of a decrease in the amount of biotin in the body are stressful situations, an unbalanced diet with an insufficient amount of biotin in products, intestinal dysbacteriosis, diseases of internal organs, disorders of the endocrine system, transferred viral diseases, taking antibiotics and other. Taking into account the above, in the complex therapy of patients with diffuse telogen alopecia, the drug «Volvit tablets» (biotin 5 mg) inside 5 mg once a day and «Volvit intensive care shampoo with biotin» were prescribed at the same time, as a result, good therapeutic results were achieved. Conclusions. Complex therapy of diffuse telogen alopecia with the simultaneous appointment of the drug «Volvit tablets» (biotin 5 mg) internally and «Volvit intensive care shampoo» with biotin externally helps to stop hair loss, restores the hair follicles to their normal function, is expedient in view of effectiveness and safety and can to be recommended for wide implementation in the practical work of doctors
Acne is a chronic inflammatory disease of the pilosebaceous unit with a multifactorial etiology and is one of the most common conditions treated by dermatologists and primary care physicians. Within an extensive and evolving treatment landscape, oral isotretinoin has demonstrated efficacy for treatment of severe, recalcitrant acne. Several side effects of isotretinoin have been reported, including laboratory abnormalities, mucocutaneous, and musculoskeletal effects, which may reduce compliance and patient satisfaction with treatment. In this narrative review, we aim to review the efficacy and safety profile of oral supplements or topical adjuvant therapies in mitigating isotretinoin-associated mucocutaneous and musculoskeletal side effects. Oral supplements reviewed include omega-3 fatty acids, vitamin E, folic acid and vitamin B12, antihistamines, l -carnitine, biotin, and combined oral supplements. Topical adjuvants include a hyaluronic acid, biosaccharide gum-2, and glycerine gel-cream; a nongreasy, noncomedogenic, fragrance-free moisturizing cream; dexpanthenol; trichloroacetic acid; and a combination cream. Most of the supplements and topical adjuvants demonstrated efficacy with an adequate level of supporting evidence and no reported adverse events, indicating an adequate safety profile. Patients on isotretinoin may benefit from using oral supplements and topical adjuvants to minimize primarily mucocutaneous side effects, increase adherence to treatment, and thereby improve overall outcomes.
We provide a comprehensive overview of inherited metabolic disorders (IMDs) in which epilepsy is a prominent manifestation. Our unique database search has identified 256 IMDs associated with various types of epilepsies, which we classified according to the classic pathophysiology-based classification of IMDs, and according to selected seizure-related factors (neonatal seizures, infantile spasms, myoclonic seizures, and characteristic EEG patterns) and treatability for the underlying metabolic defect. Our findings indicate that inherited metabolic epilepsies are more likely to present in the neonatal period, with infantile spasms or myoclonic seizures. Additionally, the ∼20% of treatable inherited metabolic epilepsies found by our search were mainly associated with the IMD groups of "cofactor and mineral metabolism" and "Intermediary nutrient metabolism." The information provided by this study, including a comprehensive list of IMDs with epilepsy stratified according to age of onset, and seizure type and characteristics, along with an overview of the key clinical features and proposed diagnostic and therapeutic approaches, may benefit any epileptologist and healthcare provider caring for individuals with metabolic conditions.
Carbon nanotubes are tube-shaped allotropic forms of carbon that have gained increasing attention in biomedical applications, especially as carriers for drug or gene delivery. However, increasing evidence indicates that carbon nanotubes have the potential to induce metabolomic toxicity, leading to dysregulation of numerous metabolic pathways, ranging from energy metabolism to amino acid biosynthesis. Here, we discuss the metabolomic toxicity of single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), with a focus on similarities and differences in their metabolic effects while aiming to reveal a broad ecological impact of carbon nanotubes not only on humans but also on fish and plants.
Previous studies indicated that in pancreatic islets the amount of glucose-derived pyruvate that enters mitochondrial metabolism via carboxylation is approximately equal to that entering via decarboxylation and that both carboxylation and decarboxylation are correlated with capacitation of glucose metabolism and insulin release. The relatively high rate of carboxylation is consistent with the current study's finding that pyruvate carboxylase is as abundant in pancreatic islets as it is in liver and kidney. Since islets do not contain phosphoenolpyruvate carboxykinase and, therefore, cannot carry out glyconeogenesis from pyruvate, the carboxylase might be present in the islet to participate in novel anaplerotic reactions. This idea was first explored by incubating mitochondria from various tissues with pyruvate. Mitochondria from tissues, such as pancreatic islets, liver, and kidney, in which pyruvate carboxylase is abundant, exported a large amount of malate and little or no citrate, isocitrate, and aspartate to the medium. The amount of malate within the mitochondria was <1% that in the medium. When pancreatic islet mitochondria were incubated with [1-¹⁴C]pyruvate, radioactive carbon appeared in the medium primarily in malate. Very little radioactivity appeared in amino acids, and little or no radioactivity appeared in citrate and isocitrate. Carbon 1 of pyruvate can be incorporated into malate and other citric acid cycle intermediates only via carboxylation, as this carbon would be lost via decarboxylation when pyruvate enters the citric acid cycle as acetyl-CoA via the pyruvate dehydrogenase reaction. The amount of malate formed equaled the ¹⁴CO2 formed and the radioactivity from C-1 of pyruvate recovered in malate slightly exceeded the formation of ¹⁴CO2 in agreement with our previous studies that reported a high rate of carboxylation of pyruvate in intact islets. When intact pancreatic islets were incubated with methyl [U-¹⁴C]succinate as a mitochondrial source of four-carbon dicarboxylic acids, radioactivity appeared in pyruvate and lactate. Taken together with previous studies, the current results suggest that during glucose-induced insulin secretion there is a shuttle operating across the mitochondrial membrane in which glucose-derived pyruvate is taken up by mitochondria and carboxylated to oxaloacetate by pyruvate carboxylase. The oxaloacetate is converted to malate which exits the mitochondrion, where, in the cytosol, it is decarboxylated to pyruvate in the reaction catalyzed by malic enzyme. This pyruvate re-enters mitochondrial pools. Such a cycle produces NADPH in the cytosol. Since it is a cycle, this shuttle can produce far more NADPH than the pentose phosphate pathway, which is known to be a very minor route of glucose metabolism in the islet. If it is accepted that this shuttle is active in the insulin cell, this implicates NADPH regeneration in insulin secretion.
From 1989 to 2001, 1 336 145 newborns were screened for biotinidase deficiency in Hungary. Fifty‐eight children with the disorder were identified as enzyme‐deficient. We have characterized the clinical and biochemical features and mutations of 20 of these children. Eleven children had profound biotinidase deficiency, 7 had partial biotinidase deficiency, and 2 were found to be heterozygous for profound deficiency by mutation analysis. Seventeen different mutations were identified in this population including seven novel mutations. Six of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was heterozygous for this mutation. Most of the children with profound deficiency have been asymptomatic on therapy; however, four exhibited minimal brain abnormalities, motor delay and abnormal blood chemistries. Compliance with therapy must be questioned in these cases. Of clinical importance, all of the children with partial deficiency exhibited mild symptoms at the time of diagnosis, at several weeks to months of age. These symptoms resolved following biotin therapy. This is in contrast to the experience in the United States, where the children with partial deficiency have been asymptomatic at the time of diagnosis. This finding further indicates that children with partial deficiency should be treated. The incidence of biotinidase deficiency in Hungary is more than twice that observed in a worldwide survey. These results indicate that newborn screening in Hungary is effective and warranted.
This book was first published in 1994. Vitamins are essential micronutrients available to animal organisms through the diet. This book takes a fresh approach to vitamin-binding proteins, with emphasis on the nature of the binding of the vitamin ligand to a protein and its sequela. The role of vitamin-binding proteins as initiators of the metabolic response is evaluated. Experts in the field from around the world present an account of their work on the interaction of vitamins with specific intracellular systems through the appropriate binding proteins and how this interaction results in the biological action of vitamins. The book will be of interest to research workers and postgraduate students in the field of biochemistry and nutrition.
Background: Marginal biotin deficiency may be a human teratogen. A biotin status indicator that is not dependent on renal function may be useful in studies of biotin status during pregnancy. A previous study of experimental biotin deficiency suggested that propionyl-coenzyme A carboxylase (PCC) activity in peripheral blood lymphocytes (PBLs) is a sensitive indicator of biotin status.
Objective: We examined the utility of measuring PCC activity and the activation of PCC by biotin in detecting marginal biotin deficiency.
Design: Marginal biotin deficiency was induced in 7 adults (3 women) by egg-white feeding for 28 d. Blood and urine were obtained on days 0, 14, and 28 (depletion phase) and 44 and 65 (repletion phase). PBLs were incubated with (activated) or without (control) biotin before PCC assay. The activation coefficient of PCC is the ratio of PCC activity in activated PBLs to that in control PBLs. The significance of differences for all measurements was tested by repeated-measures analysis of variance with Fisher’s post hoc test and Bonferroni correction.
Results: Changes in the urinary excretion of biotin and of 3-hydroxyisovaleric acid confirmed that marginal biotin deficiency was successfully induced. By day 14, PCC activity had decreased (P < 0.0001) to below the lower limit of normal in all subjects. By day 28, the activation coefficient of PCC had increased significantly (P = 0.003) and was above the upper limit of normal in 6 of 7 subjects.
Conclusion: PCC activity is the most sensitive indicator of biotin status tested to date. In future pregnancy studies, the use of lymphocyte PCC activity data should prove valuable in the assessment of biotin status.
Recent studies of biotin status during pregnancy provide evidence that a marginal degree of biotin develops in a substantial proportion of women during normal pregnancy. Several lines of evidence suggest that, although the degree of biotin deficiency is not severe enough to produce the classic cutaneous and behavioral manifestations of biotin deficiency, the deficiency is severe enough to produce metabolic derangements in women and that characteristic fetal malformations occur at a high rate in some mammals. Moreover, our analysis of data from a published multivitamin supplementation study provide significant albeit indirect evidence that the marginal degree of biotin deficiency that occurs spontaneously in normal human gestation is teratogenic. Investigation of potential mechanisms provides evidence that biotin transport by the human placenta is weak. Further, proliferating cells accumulate biotin at a rate five times faster than quiescent cells; this observation suggests that there is an increased biotin requirement associated with cell proliferation. Perhaps this requirement arises from the need to synthesize additional biotin-dependent holocarboxylases or provide additional biotin as a substrate for biotinylation of cellular histones. Reduced activity of the biotin-dependent enzymes acetyl-CoA carboxylase and propionyl-CoA carboxylase can cause alterations of lipid metabolism and might theoretically lead to alterations of polyunsaturated fatty acid and prostaglandin metabolism that derange normal skeletal development.