Template:Chembox UNII
Skeletal formula of biotin
Ball-and-stick model of the Biotin molecule
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IUPAC name
5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid
Other names
Vitamin B7; Vitamin H; Coenzyme R; Biopeiderm
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ATC code A11HA05
58-85-5 7pxY
ChEBI CHEBI:15956 7pxY
ChemSpider 149962 7pxY
DrugBank DB00121 7pxY
Jmol-3D images Image
KEGG D00029 7pxY
PubChem Template:Chembox PubChem/format
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Molar mass Lua error in Module:Math at line 495: attempt to index field 'ParserFunctions' (a nil value). g·mol−1
Appearance White crystalline needles
Melting point Script error: No such module "convert".
22 mg/100 mL
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NFPA 704

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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Biotin, also known as vitamin H or coenzyme R,[2] is a water-soluble B-vitamin (vitamin B7).

It is composed of a ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring. Biotin is a coenzyme for carboxylase enzymes, involved in the synthesis of fatty acids, isoleucine, and valine, and in gluconeogenesis.

The only human health condition for which there is strong evidence of biotin's potential benefit as a treatment is biotin deficiency.[3]

General overview

File:M. Dean Burk.jpg
Dean Burk, American biochemist who co-discovered biotin.

Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. Biotin assists in various metabolic reactions involving the transfer of carbon dioxide. It may also be helpful in maintaining a steady blood sugar level.[4] Biotin is often recommended as a dietary supplement for strengthening hair and nails, though scientific data supporting this outcome are weak. In addition to being taken as a supplement, many health & beauty products include biotin as an alternative supplement method.[5][6] Nevertheless, biotin is found in many cosmetics and health products for the hair and skin.[7][8]

Biotin deficiency is rare because, in general, intestinal bacteria produce biotin in excess of the body's daily requirements.[9] For that reason, statutory agencies in many countries, for example the USA[10] and Australia,[11] do not prescribe a recommended daily intake of biotin. However, a number of metabolic disorders exist in which an individual's metabolism of biotin is abnormal, such as deficiency in the holocarboxylase synthetase enzyme which covalently links biotin onto the carboxylase, where the biotin acts as a cofactor.[12]

High doses of biotin may play a role in stopping and reversing progression in progressive multiple sclerosis, as shown in a small pilot study of 23 patients in France. 91% of these patients were judged to have improved clinically. There was a 2 to 8 month lag in improvements. There are few treatment options for progressive MS. [13]


Biotin has an unusual structure (see above figure), with two rings fused together via one of their sides. The two rings are ureido and thiophene moieties. Biotin is a heterocyclic, S-containing monocarboxylic acid. It is made from two precursors, alanine and pimeloyl-CoA via three enzymes. 8-Amino-7-oxopelargonic acid synthase is a pyridoxal 5'-phosphate enzyme. The pimeloyl-CoA, could be produced by a modified fatty acid pathway involving a malonyl thioester as the starter. 7,8Diaminopelargonic acid (DAPA) aminotransferase is unusual in using S-adenosyl methionine (SAM) as the NH2 donor. Dethiobiotin synthethase catalyzes the formation of the ureido ring via a DAPA carbamate activated with ATP. Biotin synthase reductively cleaves SAM into a deoxyadenosyl radical—a first radical formed on dethiobiotin is trapped by the sulfur donor, which was found to be the iron-sulfur (Fe-S) center contained in the enzyme.[14]

Cofactor biochemistry

D-(+)-Biotin is a cofactor responsible for carbon dioxide transfer in several carboxylase enzymes:

Biotin is important in fatty acid synthesis, branched-chain amino acid catabolism, and gluconeogenesis. It covalently attaches to the epsilon-amino group of specific lysine residues in these carboxylases. This biotinylation reaction requires ATP and is catalyzed by holocarboxylase synthetase.[15] In bacteria, biotin is attached to biotin carboxyl carrier protein (BCCP) by biotin protein ligase (BirA in E. coli).[16] The attachment of biotin to various chemical sites, biotinylation, is used as an important laboratory technique to study various processes, including protein localization, protein interactions, DNA transcription, and replication. Biotinidase itself is known to be able to biotinylate histone proteins,[17] but little biotin is found naturally attached to chromatin.

Biotin binds very tightly to the tetrameric protein avidin (also streptavidin and neutravidin), with a dissociation constant Kd on the order of 10−15 M, which is one of the strongest known protein-ligand interactions.[18] This is often used in different biotechnological applications. Until 2005, very harsh conditions were thought to be required to break the biotin-streptavidin bond.[19]

Sources of biotin

Biotin is consumed from a wide range of food sources in the diet, but few are particularly rich sources. Foods with a relatively high biotin content include peanuts, Swiss chard and other leafy green vegetables, raw egg yolk (however, the consumption of avidin-containing egg whites with egg yolks minimizes the effectiveness of egg yolk's biotin in one's body), liver, and Saskatoon berries. The dietary biotin intake in Western populations has been estimated to be 35 to 70 μg/d (143–287 nmol/d).[20]

Biotin is also available in supplement form and can be found in most pharmacies. The synthetic process developed by Leo Sternbach and Moses Wolf Goldberg in the 1940s uses fumaric acid as a starting material.[21]


Biotin is also called vitamin H (the H represents Haar und Haut, German words for "hair and skin") or vitamin B7. Studies on its bioavailability have been conducted in rats and in chicks. Based on these studies, biotin bioavailability may be low or variable, depending on the type of food being consumed. In general, biotin exists in food as protein-bound form or biocytin.[22] Proteolysis by protease is required prior to absorption. This process assists free biotin release from biocytin and protein-bound biotin. The biotin present in corn is readily available; however, most grains have about a 20-40% bioavailability of biotin.[23]

The wide variability in biotin bioavailability may be due to the ability of an organism to break various biotin-protein bonds from food. Whether an organism has an enzyme with that ability will determine the bioavailability of biotin from the foodstuff.[23]

Factors that affect biotin requirements

The frequency of marginal biotin status is not known, but the incidence of low circulating biotin levels in alcoholics has been found to be much greater than in the general population. Also, relatively low levels of biotin have been reported in the urine or plasma of patients who have had a partial gastrectomy or have other causes of achlorhydria, burn patients, epileptics, elderly individuals, and athletes.[23] 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. Additionally, smoking may further accelerate biotin catabolism in women.[24]


Biotin deficiency can arise due to various inborn genetic errors that affect the activity of biotin-related enzymes. Since endogenous biotin production occurs in the gut, dysbiosis could also upset the metabolic processes that allow the body to generate biotin on its own.

The first demonstration of biotin deficiency in animals was observed in animals fed raw egg white. Rats fed egg white protein were found to develop dermatitis, alopecia and neuromuscular dysfunction. This syndrome, called egg white injury, was discovered to be caused by a glycoprotein found in egg white, avidin. Avidin denatures upon heating (cooking). This protein binds extremely well with biotin, making it unavailable for use in enzymatic reactions.[3]

Regardless of the root cause, the deficiency can usually be addressed directly with nutritional supplementation.

Deficiency symptoms include:

  • Hair loss (alopecia)
  • Conjunctivitis
  • Dermatitis in the form of a scaly, red rash around the eyes, nose, mouth, and genital area.
  • Neurological symptoms in adults, such as depression, lethargy, hallucination, and numbness and tingling of the extremities[10]

The neurological and psychological symptoms can occur with only mild deficiencies. Dermatitis, conjunctivitis, and hair loss will generally occur only when deficiency becomes more severe. In severe cases of deficiency, a characteristic facial rash, together with an unusual facial fat distribution, may also be present (this has been termed the "biotin-deficient face" by some experts) (no citation provided).

Individuals with hereditary disorders of biotin deficiency have evidence of impaired immune system function, including increased susceptibility to bacterial and fungal infections.[25]

Pregnant women tend to have a high risk of biotin deficiency. Nearly half of pregnant women have abnormal increases of 3-hydroxyisovaleric acid, which reflects reduced status of biotin.[25] Several studies have reported this possible biotin deficiency during the pregnancy may cause infants' congenital malformations, such as cleft palate. Mice fed with dried raw egg to induce biotin deficiency during the gestation resulted in up to 100% incidence of the infants' malnourishment. Infants and embryos are more sensitive to the biotin deficiency. Therefore, even a mild level of the mother's biotin deficiency that does not reach the appearance of physiological deficiency signs may cause a serious consequence in the infants.

Metabolic disorders

Inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed multiple carboxylase deficiency. These include deficiencies in the enzymes holocarboxylase synthetase or biotinidase. Holocarboxylase synthetase deficiency prevents the body's cells from using biotin effectively, and thus interferes with multiple carboxylase reactions.[26] Biochemical and clinical manifestations include: ketolactic acidosis, organic aciduria, hyperammonemia, skin rash, feeding problems, hypotonia, seizures, developmental delay, alopecia, and coma.

Biotinidase deficiency is not due to inadequate biotin, but rather to a deficiency in the enzymes that process it. 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.[26] General symptoms include decreased appetite and growth. Dermatologic symptoms include dermatitis, alopecia, and achromotrichia (absence or loss of pigment in the hair).[27] Perosis (a shortening and thickening of bones) is seen in the skeleton. Fatty liver and kidney syndrome and hepatic steatosis also can occur.[23]

Use in biotechnology

Biotin is widely used throughout the biotechnology industry to conjugate proteins for biochemical assays.[28] Biotin's small size means the biological activity of the protein will most likely be unaffected. This process is called biotinylation. Because both streptavidin and avidin bind biotin with high affinity (Kd of 10−14 mol/l to 10−15 mol/l) and specificity, biotinylated proteins of interest can be isolated from a sample by exploiting this highly stable interaction. The sample is incubated with streptavidin/avidin beads, allowing capture of the biotinylated protein of interest. Any other proteins binding to the biotinylated molecule will also stay with the bead and all other unbound proteins can be washed away. However, due to the extremely strong streptavidin-biotin interaction, very harsh conditions are needed to elute the biotinylated protein from the beads (typically 6M guanidine HCl at pH 1.5), which often will denature the protein of interest. To circumvent this problem, beads conjugated to monomeric avidin can be used, which has a decreased biotin-binding affinity of ~10−8 mol/l, allowing the biotinylated protein of interest to be eluted with excess free biotin.

ELISAs often make use of biotinylated secondary antibodies against the antigen of interest, followed by a detection step using streptavidin conjugated to a reporter molecule, such as horseradish peroxidase or alkaline phosphatase.


Animal studies have indicated few, if any, effects due to high level doses of biotin. This may provide evidence that both animals and humans could tolerate doses of at least an order of magnitude greater than each of their nutritional requirements. There are no reported cases of adverse effects from receiving high doses of the vitamin, in particular, when used in the treatment of metabolic disorders causing sebhorrheic dermatitis in infants.[29]excess biotin accumulation can inhibit endogenous sirt activity leading to increased inflammation, cellularity, and collagen deposition and may be partly responsible for age related metabolic problems. Reversed by calorie restriction in mice.[30]

See also


  1. ^ Merck Index, 11th Edition, 1244.
  2. ^ "Biotin". The Free Medical Dictionary. Retrieved 2011-10-10. 
  3. ^ a b "Biotin: MedlinePlus Supplements". 13 September 2013. Retrieved 2013-09-29. 
  4. ^
  5. ^ "Vitamin H (Biotin)". University of Maryland Medical Center. 1 June 2011. Retrieved 4 May 2012. 
  6. ^ "Biotin|". WebMD. Retrieved 4 May 2012. 
  7. ^ Fiume MZ (2001). "Final report on the safety assessment of biotin". International Journal of Toxicology 2: 45–61. PMID 11800048. Retrieved 17 October 2014. 
  8. ^ "Hair Growth With Biotin". Retrieved 8 July 2014. 
  9. ^ "Biotin Deficiency". Medscape. 1 August 2011. Retrieved 3 May 2012. 
  10. ^ a b Otten, JJ, Hellwig, JP and Meyers, LD., ed. (2006). Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. The National Academies Press. ISBN 0-309-10091-7. 
  11. ^ National Health and Medical Research Council: Nutrient Reference Values for Australia and New Zealand
  12. ^ Zempleni J, Hassan YI, Wijeratne SS (2008). "Biotin and biotinidase deficiency". Expert Rev Endocrinol Metab 3 (6): 715–724. PMC 2726758. PMID 19727438. doi:10.1586/17446651.3.6.715. 
  13. ^
  14. ^ Marquet A, Bui BT, Florentin D (2001). "Biosynthesis of biotin and lipoic acid". Vitam. Horm. Vitamins & Hormones 61: 51–101. ISBN 978-0-12-709861-6. PMID 11153271. doi:10.1016/S0083-6729(01)61002-1. 
  15. ^ Zempleni J, Wijeratne SS, Hassan YI (2009). "Biotin". BioFactors 35 (1): 36–46. PMID 19319844. doi:10.1002/biof.8. 
  16. ^ Chapman-Smith A, Cronan JE (1999). "Molecular biology of biotin attachment to proteins". J. Nutr. 129 (2S Suppl): 477S–484S. PMID 10064313. 
  17. ^ Hymes J, Fleischhauer K, Wolf B (1995). "Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency". Biochem Mol Med. 56 (1): 76–83. PMID 8593541. doi:10.1006/bmme.1995.1059. 
  18. ^ Laitinen OH, Hytönen VP, Nordlund HR, Kulomaa MS (2006). "Genetically engineered avidins and streptavidins". Cell Mol Life Sci. 63 (24): 2992–3017. PMID 17086379. doi:10.1007/s00018-006-6288-z. 
  19. ^ Holmberg A, Blomstergren A, Nord O, Lukacs M, Lundeberg J, Uhlén M (2005). "The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures". Electrophoresis 26 (3): 501–10. PMID 15690449. doi:10.1002/elps.200410070. 
  20. ^ Zempleni J, Mock DM (1999). "Biotin biochemistry and human requirements". J Nutr Biochem. 10 (3): 128–138. PMID 15539280. doi:10.1016/S0955-2863(98)00095-3. 
  21. ^ "Biotin". 2014-03-19. Retrieved 2014-03-19. 
  22. ^ Gropper S.S., Smith, J.L.,Groff, J.L. (2005). Advanced nutrition and human metabolism. Belmont. ISBN 0-534-55986-7. 
  23. ^ a b c d Combs, Gerald F. Jr. (2008). The Vitamins: Fundamental Aspects in Nutrition and Health. San Diego: Elsevier, Inc. ISBN 978-0-12-183493-7. 
  24. ^ Bowman, BA and Russell, RM., ed. (2006). "Biotin". Present Knowledge in Nutrition, Ninth Edition, Vol 1. Washington, DC: International Life Sciences Institute. ISBN 978-1-57881-198-4. 
  25. ^ a b Higdon, Jane (2003). "Biotin". An evidence-based approach to vitamins and minerals. Thieme. ISBN 978-1-58890-124-8. 
  26. ^ a b Wolf B, Grier RE, Secor McVoy JR, Heard GS (1985). "Biotinidase deficiency: a novel vitamin recycling defect". J Inherit Metab Dis. 8 (1): 53–8. PMID 3930841. doi:10.1007/BF01800660. 
  27. ^
  28. ^ "Overview of Protein Labeling". Thermo Fisher Scientific. Retrieved 22 April 2012. 
  29. ^ Combs, Gerald F. Jr. (1998). The Vitamins: Fundamental Aspects in Nutrition and Health. Ithaca: Elsevier Academic Press. ISBN 0-12-183492-1. pg. 360
  30. ^ Diabetes 2015;64:1-15

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