biotin biotin biotin names preferred iupac name 5-imidazol-4-yl]pentanoic acid other names vitamin b7 identifiers cas number 58-85-5 y 3d model (jsmol) interactive imageinteractive image chebi chebi:15956 y chembl chembl857 y chemspider 149962 y drugbank db00121 y echa infocard 100.000.363 iuphar/bps 4787 kegg d00029 y pubchem cid 171548 unii 6so6u10h04 y comptox dashboard (epa) dtxsid7022679 inchi inchi=1s/c10h16n2o3s/c13-8(14)4-2-1-3-7-9-6(5-16-7)11-10(15)12-9/h6-7,9h,1-5h2,(h,13,14)(h2,11,12,15)/t6-,7-,9-/m0/s1 ykey: ybjhbahktgyvgt-zkwxmuahsa-n yinchi=1/c10h16n2o3s/c13-8(14)4-2-1-3-7-9-6(5-16-7)11-10(15)12-9/h6-7,9h,1-5h2,(h,13,14)(h2,11,12,15)/t6-,7-,9-/m0/s1key: ybjhbahktgyvgt-zkwxmuahbb smiles o=c1n2(sc2n1)ccccc(=o)oc12((s1)ccccc(=o)o)nc(=o)n2 properties chemical formula c10h16n2o3s molar mass 244.31 g·mol−1 appearance white crystalline needles melting point 232 to 233 °c (450 to 451 °f; 505 to 506 k) solubility in water 22 mg/100 ml pharmacology atc code a11ha05 (who) hazards nfpa 704 (fire diamond) 1 1 0 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). y verify (what is yn ?) infobox references biotin (or vitamin b7) is one of the b vitamins. it is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. the name biotin, borrowed from the german biotin, derives from the ancient greek word βίοτος (bíotos; 'life') and the suffix "-in" (a suffix used in chemistry usually to indicate 'forming'). chemical description biotin is classified as a heterocyclic compound, with a sulfur-containing ring fused ureido and tetrahydrothiophene group. a c5-carboxylic acid side chain is appended to one of the rings. the ureido ring, containing the −n−co−n− group, serves as the carbon dioxide carrier in carboxylation reactions. biotin is a coenzyme for five carboxylase enzymes, which are involved in the catabolism of amino acids and fatty acids, synthesis of fatty acids, and gluconeogenesis. biotinylation of histone proteins in nuclear chromatin plays a role in chromatin stability and gene expression. dietary recommendations the us national academy of medicine updated dietary reference intakes for many vitamins in 1998. at that time there was insufficient information to establish estimated average requirement or recommended dietary allowance, terms that exist for most vitamins. in instances such as this, the academy sets adequate intakes (ais) with the understanding that at some later date, when the physiological effects of biotin are better understood, ais will be replaced by more exact information. the biotin ais for both males and females are: 5 μg/day of biotin for 0-to-6-month-olds, 6 μg/day of biotin for 7-to-12-month-olds, 8 μg/day of biotin for 1-to-3-year-olds, 12 μg/day of biotin for 4-to-8-year-olds, 20 μg/day of biotin for 9-to-13-year-olds, 25 μg/day of biotin for 14-to-18-year-olds, and 30 μg/day of biotin for those 19 years old and older. the biotin ais for females who are either pregnant or lactating, respectively, are: 30 μg/day of biotin for pregnant females 14-to-50-years old and 35 μg/day of biotin for lactating females 14-to-50-years old. australia and new zealand set ais similar to the us. the european food safety authority (efsa) also identifies ais, setting values at 40 μg/day for adults, pregnancy at 40 μg/day, and breastfeeding at 45 μg/day. for children ages 1–17 years, the ais increase with age from 20 to 35 μg/day. safety the us national academy of medicine estimates upper limits for vitamins and minerals when evidence for a true limit is sufficient. for biotin, however, there is no upper limit because adverse effects of high biotin intake have not been determined. the efsa also reviewed safety and reached the same conclusion as in the united states. labeling regulations for us food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of daily value. for biotin labeling purposes 100% of the daily value was 300 μg/day, but as of may 27, 2016, it was revised to 30 μg/day to bring it into an agreement with the adequate intake. compliance with the updated labeling regulations was required by january 1, 2020, for manufacturers with us$10 million or more in annual food sales, and by january 1, 2021, for manufacturers with lower volume food sales. a table of the old and new adult daily values is provided at reference daily intake. sources source amount (μg / 100 g) chicken liver187 beef liver42 eggs21 egg white5.8 egg yolk27 salmon, canned in water5.9 pork chop4.5 turkey breast0.7 tuna, white, canned0.7 source amount (μg / 100 g) peanuts, roasted17.5 sunflower seeds, roasted7.8 almonds, roasted4.4 sweet potato1.5 broccoli0.9 tomato0.7 strawberry1.5 avocado1.0 corn, canned0.05 source amount (μg / 100 g) cheese1.4 milk0.1 corn flakes cereal0.1 oatmeal0.1 bread0.1 french fries0.3 wine0.1 beer0.1 potatoes, mashed0.1 biotin is stable at room temperature and is not destroyed by cooking. the dietary biotin intake in western populations has been estimated to be in the range of 35 to 70 μg/day. nursing infants ingest about 6 μg/day. biotin is available in dietary supplements, individually or as an ingredient in multivitamins. no government fortification programs according to the global fortification data exchange, biotin deficiency is so rare that no countries require that foods be fortified. physiology biotin is a water-soluble b vitamin. consumption of large amounts as a dietary supplement results in absorption, followed by excretion into urine as biotin. consumption of biotin as part of a normal diet results in urinary excretion of biotin and biotin metabolites. absorption biotin in food is bound to proteins. digestive enzymes reduce the proteins to biotin-bound peptides. the intestinal enzyme biotinidase, found in pancreatic secretions and in the brush border membranes of all three parts of the small intestine, frees biotin, which is then absorbed from the small intestine. when consumed as a biotin dietary supplement, absorption is nonsaturable, meaning that even very high amounts are absorbed effectively. transport across the jejunum is faster than across the ileum. the large intestine microbiota synthesize amounts of biotin estimated to be similar to the amount taken in the diet, and a significant portion of this biotin exists in the free (protein-unbound) form and, thus, is available for absorption. how much is absorbed in humans is unknown, although a review did report that human epithelial cells of the colon in vitro demonstrated an ability to uptake biotin. once absorbed, sodium-dependent multivitamin transporter (smvt) mediates biotin uptake into the liver. smvt also binds pantothenic acid, so high intakes of either of these vitamins can interfere with transport of the other. metabolism and excretion biotin catabolism occurs via two pathways. in one, the valeric acid sidechain is cleaved, resulting in bisnorbiotin. in the other pathway, the sulfur is oxidized, resulting in biotin sulfoxide. urine content is proportionally about half biotin, plus bisnorbiotin, biotin sulfoxide, and small amounts of other metabolites. factors that affect biotin requirements chronic alcohol use is associated with a significant reduction in plasma biotin. intestinal biotin uptake also appears to be sensitive to the effect of the anti-epilepsy drugs carbamazepine and primidone. relatively low levels of biotin have also been reported in the urine or plasma of patients who have had a partial gastrectomy or have other causes of achlorhydria, as well as burn patients, elderly individuals, and athletes. pregnancy and lactation may be associated with an increased demand for biotin. in pregnancy, this may be due to a possible acceleration of biotin catabolism, whereas, in lactation, the higher demand has yet to be elucidated. recent studies have shown marginal biotin deficiency can be present in human gestation, as evidenced by increased urinary excretion of 3-hydroxyisovaleric acid, decreased urinary excretion of biotin and bisnorbiotin, and decreased plasma concentration of biotin. biosynthesis biotin, synthesized in plants, is essential to plant growth and development. bacteria also synthesize biotin, and it is thought that bacteria resident in the large intestine may synthesize biotin that is absorbed and utilized by the host organism. synthesis starts from two precursors, alanine and pimeloyl-coa. these form 7-keto-8-aminopelargonic acid (kapa). kapa is transported from plant peroxisomes to mitochondria where it is converted to 7,8-diaminopelargonic acid (dapa). the enzyme dethiobiotin synthetase catalyzes the formation of the ureido ring via a dapa carbamate activated with atp, creating dethiobiotin, which is then converted into biotin. the last step is catalyzed by biotin synthase, a radical sam enzyme. the sulfur is donated by an unusual ferredoxin. cofactor biochemistry the enzyme holocarboxylase synthetase covalently attaches biotin to five human carboxylase enzymes: acetyl-coa carboxylase alpha (acc1) acetyl-coa carboxylase beta (acc2) pyruvate carboxylase (pc) methylcrotonyl-coa carboxylase (mcc) propionyl-coa carboxylase (pcc) for the first two, biotin serves as a cofactor responsible for transfer of bicarbonate to acetyl-coa, converting it to malonyl-coa for fatty acid synthesis. pc participates in gluconeogenesis. mcc catalyzes a step in leucine metabolism. pcc catalyzes a step in the metabolism of propionyl-coa. metabolic degradation of the biotinylated carboxylases leads to the formation of biocytin. this compound is further degraded by biotinidase to release biotin, which is then reutilized by holocarboxylase synthetase. biotinylation of histone proteins in nuclear chromatin is a posttranslational modification that plays a role in chromatin stability and gene expression. deficiency main article: biotin deficiency primary biotin deficiency, meaning deficiency as a consequence of too little biotin in the diet, is rare, because biotin is contained in so many foods. subclinical deficiency can cause mild symptoms, such as hair thinning, brittle fingernails, or skin rash, typically on the face. aside from inadequate dietary intake (rare), deficiency of biotin can be caused by a genetic disorder that affects biotin metabolism. the most common among these is biotinidase deficiency. low activity of this enzyme causes a failure to recycle biotin from biocytin. rarer are carboxylase and biotin transporter deficiences. neonatal screening for biotinidase deficiency started in the united states in 1984, with many countries now also testing for this genetic disorder at birth. treatment is lifelong dietary supplement with biotin. diagnosis low serum and urine biotin are not sensitive indicators of inadequate biotin intake. however, serum testing can be useful for confirmation of consumption of biotin-containing dietary supplements, and whether a period of refraining from supplement use is long enough to eliminate the potential for interfering with drug tests. indirect measures depend on the biotin requirement for carboxylases. 3-methylcrotonyl-coa is an intermediate step in the catabolism of the amino acid leucine. in the absence of biotin, the pathway diverts to 3-hydroxyisovaleric acid. urinary excretion of this compound is an early and sensitive indicator of biotin deficiency. deficiency as a result of metabolic disorders biotinidase deficiency is a deficiency of the enzyme that recycles biotin, the consequence of an inherited genetic mutation. biotinidase catalyzes the cleavage of biotin from biocytin and biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby recycles biotin. it is also important in freeing biotin from dietary protein-bound biotin. neonatal screening for biotinidase deficiency started in the united states in 1984, which as of 2017 was reported as required in more than 30 countries. profound biotinidase deficiency, defined as less than 10% of normal serum enzyme activity, which has been reported as 7.1 nmol/min/ml, has an incidence of 1 in 40,000 to 1 in 60,000, but with rates as high as 1 in 10,000 in countries with high incidence of consanguineous marriages (second cousin or closer). partial biotinidase deficiency is defined as 10% to 30% of normal serum activity. incidence data stems from government mandated newborn screening. for profound deficiency, treatment is oral dosing with 5 to 20 mg per day. seizures are reported as resolving in hours to days, with other symptoms resolving within weeks. treatment of partial biotinidase deficiency is also recommended even though some untreated people never manifest symptoms. lifelong treatment with supplemental biotin is recommended for both profound and partial biotinidase deficiency. inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed multiple carboxylase deficiency. these include deficiencies in the enzymes holocarboxylase synthetase. holocarboxylase synthetase deficiency prevents the body's cells from using biotin effectively and thus interferes with multiple carboxylase reactions. there can also be a genetic defect affecting the sodium-dependent multivitamin transporter protein. biochemical and clinical manifestations of any of these metabolic disorders can include ketolactic acidosis, organic aciduria, hyperammonemia, rash, hypotonia, seizures, developmental delay, alopecia and coma. use in biotechnology chemically modified versions of biotin are widely used throughout the biotechnology industry to isolate proteins and non-protein compounds for biochemical assays. because egg-derived avidin binds strongly to biotin with a dissociation constant kd ≈ 10−15 m, biotinylated compounds of interest can be isolated from a sample by exploiting this highly stable interaction. first, the chemically modified biotin reagents are bound to the targeted compounds in a solution via a