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Canadian Journal of Physiology and... Dec 2015Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the... (Review)
Review
Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear protein involved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.
Topics: Animals; Biotin; Biotinidase; Biotinylation; Humans; Inflammation; Transcription Factors
PubMed: 26168302
DOI: 10.1139/cjpp-2014-0460 -
The Journal of Chemical Physics May 2022Biotin-labeled proteins are widely used as tools to study protein-protein interactions and proximity in living cells. Proteomic methods broadly employ proximity-labeling...
Biotin-labeled proteins are widely used as tools to study protein-protein interactions and proximity in living cells. Proteomic methods broadly employ proximity-labeling technologies based on protein biotinylation in order to investigate the transient encounters of biomolecules in subcellular compartments. Biotinylation is a post-translation modification in which the biotin molecule is attached to lysine or tyrosine residues. So far, biotin-based technologies proved to be effective instruments as affinity and proximity tags. However, the influence of biotinylation on aspects such as folding, binding, mobility, thermodynamic stability, and kinetics needs to be investigated. Here, we selected two proteins [biotin carboxyl carrier protein (BCCP) and FKBP3] to test the influence of biotinylation on thermodynamic and kinetic properties. Apo (without biotin) and holo (biotinylated) protein structures were used separately to generate all-atom structure-based model simulations in a wide range of temperatures. Holo BCCP contains one biotinylation site, and FKBP3 was modeled with up to 23 biotinylated lysines. The two proteins had their estimated thermodynamic stability changed by altering their energy landscape. In all cases, after comparison between the apo and holo simulations, differences were observed on the free-energy profiles and folding routes. Energetic barriers were altered with the density of states clearly showing changes in the transition state. This study suggests that analysis of large-scale datasets of biotinylation-based proximity experiments might consider possible alterations in thermostability and folding mechanisms imposed by the attached biotins.
Topics: Biotin; Escherichia coli; Kinetics; Proteomics; Thermodynamics
PubMed: 35597640
DOI: 10.1063/5.0083875 -
Seminars in Dermatology Dec 1991This article reviews current knowledge concerning the dermatologic manifestations of biotin deficiency. Biotin is a water-soluble vitamin that acts as an essential... (Review)
Review
This article reviews current knowledge concerning the dermatologic manifestations of biotin deficiency. Biotin is a water-soluble vitamin that acts as an essential cofactor for four carboxylases, each of which catalyzes an essential step in intermediary metabolism. For example, acetyl-CoA carboxylase catalyzes the rate-limiting step in fatty acid elongation. In infants, children, and adults, deficiency of biotin causes alopecia and a characteristic scaly, erythematous dermatitis distributed around body orifices. The rash closely resembles that of zinc deficiency. Candida albicans often can be cultured from the skin lesions. Biotinidase deficiency, an inborn error, causes biotin deficiency, probably as a consequence of unpaired intestinal absorption, cellular salvage, and renal reclamation of biotin; biotinidase deficiency causes dermatologic manifestations similar to biotin deficiency. There is evidence that impaired fatty acid metabolism secondary to reduced activities of the biotin-dependent carboxylases (especially acetyl-CoA carboxylase) plays an etiologic role in the dermatologic manifestations of biotin deficiency. Candida infections secondary to impaired immune function might also contribute to the dermatitis of biotin deficiency.
Topics: Adult; Biotin; Child; Humans; Infant; Metabolism, Inborn Errors; Skin Diseases
PubMed: 1764357
DOI: No ID Found -
The Journal of Dermatology Apr 2005Biotin deficiency is rarely encountered in an infant on weaning from breast and formula feeding. It is characterized by alopecia and scaly, erythematous dermatitis... (Review)
Review
Biotin deficiency is rarely encountered in an infant on weaning from breast and formula feeding. It is characterized by alopecia and scaly, erythematous dermatitis distributed around the body orifices. We report a 5-month-old Japanese infant with typical skin lesions who had been diagnosed as a neonate with dyspepsia and fed only an amino acid formula. Serum and urine levels of biotin were below the normal range, but zinc and biotinidase were within normal range. Urinary excretion of 3-methylcrotonylglycine, 3-hydroxyisovaleric acid, and methylcitric acid was significantly elevated. Daily oral supplementation with 1 mg of biotin resulted in dramatic improvement of the periorificial dermatitis and hair growth together with a complete disappearance of the organic aciduria. Our case shows that the characteristic skin manifestations are the most important clue to the diagnosis of biotin deficiency and demonstrated that urinary excretion of biotin and organic aciduria, rather than the serum concentration of biotin, are the sensitive indicators for evaluating the patient's status of biotin deficiency.
Topics: Biotin; Deficiency Diseases; Dietary Supplements; Erythema; Facial Dermatoses; Humans; Infant; Infant Formula; Male; Peritoneum
PubMed: 15863846
DOI: 10.1111/j.1346-8138.2005.tb00758.x -
The Journal of Nutrition Feb 1999This review describes our knowledge of biotin transport in the small intestine of humans and other mammals and presents recent findings in the area. Previous studies... (Review)
Review
This review describes our knowledge of biotin transport in the small intestine of humans and other mammals and presents recent findings in the area. Previous studies have shown that biotin transport across the brush border membrane of the small intestinal absorptive cells occurs via a carrier-mediated, Na+ gradient-dependent, electroneutral mechanism. Exit of biotin out of the enterocyte, i.e., transport across the basolateral membrane, also occurs via a carrier-mediated process, but the process is Na+ independent and electrogenic. Recent studies from our laboratory have shown that the uptake process of biotin in Caco-2 cells, a human-derived cultured intestinal epithelial cell line, are under the cellular regulation of both a protein kinase C- and a Ca/calmodulin-mediated pathway. In addition, the uptake process is shared by another water-soluble vitamin, pantothenic acid. For the first time, other recent studies have detected the existence of a Na+-dependent, carrier-mediated mechanism for biotin uptake at the apical membrane of colonocytes, which could theoretically mediate absorption of the biotin synthesized by colonic microflora. This system was again found to be shared by pantothenic acid, which is also synthesized by the normal microflora of the large intestine.
Topics: Animals; Bacteria; Biological Transport; Biotin; Diet; Humans; Intestinal Absorption; Intestine, Large; Intestine, Small
PubMed: 10064315
DOI: 10.1093/jn/129.2.490S -
The Journal of Biological Chemistry Jun 1954
Topics: Biotin; Oxidation-Reduction
PubMed: 13174559
DOI: No ID Found -
Annual Review of Nutrition 2005Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene... (Review)
Review
Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have been identified in various human tissues. Many biotin-dependent gene products play roles in signal transduction and localize to the cell nucleus, consistent with a role for biotin in cell signaling. Posttranscriptional events related to ribosomal activity and protein folding may further contribute to effects of biotin on gene expression. Finally, research has shown that biotinidase and holocarboxylase synthetase mediate covalent binding of biotin to histones (DNA-binding proteins), affecting chromatin structure; at least seven biotinylation sites have been identified in human histones. Biotinylation of histones appears to play a role in cell proliferation, gene silencing, and the cellular response to DNA repair. Roles for biotin in cell signaling and chromatin structure are consistent with the notion that biotin has a unique significance in cell biology.
Topics: Animals; Biotin; Biotinylation; Cell Membrane; Central Nervous System; Histones; Homeostasis; Humans; Organelles; Signal Transduction; Symporters
PubMed: 16011464
DOI: 10.1146/annurev.nutr.25.121304.131724 -
Methods in Enzymology 1990
Topics: Biotin; Chemical Phenomena; Chemistry; Indicators and Reagents; Molecular Structure; Structure-Activity Relationship; Succinimides
PubMed: 2388566
DOI: 10.1016/0076-6879(90)84267-k -
Annual Review of Nutrition 1988
Review
Topics: Acetyl-CoA Carboxylase; Animals; Biotin; Female; Humans; Male; Pyruvate Carboxylase
PubMed: 2904822
DOI: 10.1146/annurev.nu.08.070188.001235 -
Clinical Chemistry Feb 2017
Topics: Biotin; Diagnostic Tests, Routine; Dietary Supplements; Humans
PubMed: 28130485
DOI: 10.1373/clinchem.2016.267286