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Revision as of 18:55, 29 November 2010
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| File:Biotin 3D Molecule.png | |
| Names | |
|---|---|
| IUPAC name
5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid
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| Other names
Vitamin B7; Vitamin H; Coenzyme R; Biopeiderm
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| Identifiers | |
3D model (JSmol)
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| ChemSpider | |
| ECHA InfoCard | 100.000.363 |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C10H16N2O3S | |
| Molar mass | 244.31 g·mol−1 |
| Appearance | White crystalline needles |
| Melting point | 232-233 °C |
| 22 mg/100 mL | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Biotin is a water-soluble B-complex vitamin (vitamin B7) that 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 in the metabolism of fatty acids and leucine, and it plays a role in gluconeogenesis.
General overview
Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. It plays a role in the citric acid cycle, which is the process by which biochemical energy is generated during aerobic respiration. Biotin not only assists in various metabolic reactions but also helps to transfer carbon dioxide. Biotin may also be helpful in maintaining a steady blood sugar level.[2] Biotin is often recommended for strengthening hair and nails. Consequently, it is found in many cosmetics and health products for the hair and skin, though it cannot be absorbed through the hair or skin itself.
Biotin deficiency is rare, because intestinal bacteria generally produce biotin in excess of the body's daily requirements. For that reason, statutory agencies in many countries, for example the USA[3] and Australia,[4] 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; in these disorders, megadoses of biotin, far higher than the average daily intake from food, can generally mitigate symptoms and correct the underlying metabolic disturbance.
Biochemistry
Biotin D(+) is a cofactor responsible for carbon dioxide transfer in several carboxylase enzymes:
- Acetyl-CoA carboxylase alpha
- Acetyl-CoA carboxylase beta
- Methylcrotonyl-CoA carboxylase
- Phosphoenolpyruvate carboxylase
- Propionyl-CoA carboxylase
- Pyruvate carboxylase
and, so, is important in fatty acid synthesis, branched-chain amino acid catabolism, and gluconeogenesis. Biotin 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.[5] The attachment of biotin to various chemical sites can be 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,[6] 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 in the order of 10−15, which is one of the strongest known protein-ligand interactions, approaching the covalent bond in strength.[7] This is often used in different biotechnological applications. Until 2005, very harsh conditions were required to break the biotin-streptavidin bond.[8]
Sources of biotin
Biotin is consumed from a wide range of food sources in the diet, however there are few particularly rich sources. Foods with a relatively high biotin content include raw egg yolk (ironically, the consumption of egg whites with egg yolks minimizes the effectiveness of egg yolk's biotin in one's body), liver, and some vegetables[citation needed][vague]. The dietary biotin intake in Western populations has been estimated to be 35 to 70 μg/d (143–287 nmol/d).[9]
Biotin is also available from supplements. The synthetic process developed by Leo Sternbach and Moses Wolf Goldberg in the 1940s uses fumaric acid as a starting material and is identical to the natural product.[10]
Bioavailability
Biotin is also called vitamin H (the H represents "Haar und Haut”, German words for “hair and skin”) or vitamin B7. Studies on the bioavailability of biotin have been conducted in rats and in chicks. From these studies, it was concluded that 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.[11] 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 grain have about a 20-40% bioavailability of biotin.[12]
A possible explanation for the wide variability in biotin bioavailability is that it is due to ability of an organism to break various biotin-protein bonds from food. Whether an organism has an enzyme with the ability to break that bond will determine the bioavailability of biotin from the foodstuff.[12]
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 that have had partial gastrectomy or that have other causes of achlorhydria, burn patients, epileptics, elderly individuals, and athletes.[12] 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 that 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.[13]
Deficiency
Biotin deficiency is relatively rare and mild, and can be addressed with supplementation. Such deficiency can be caused by the excessive consumption of raw egg whites (20 eggs/day would be required to induce it), which contain high levels of the protein avidin, which binds biotin strongly. Avidin denaturates upon heating (cooking), while the biotin remains intact.
Symptoms of overt biotin deficiency 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.[3]
The characteristic facial rash, together with an unusual facial fat distribution, has been termed the "biotin-deficient face" by some experts. Individuals with hereditary disorders of biotin deficiency have evidence of impaired immune system function, including increased susceptibility to bacterial and fungal infections.[14]
Pregnant women tend to have high risk of biotin deficiency. Research has shown that nearly half of pregnant women have an abnormal increase of 3-hydroxyisovaleric acid, which reflects reduced status of biotin.[14] Numbers of studies reported that 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 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.[15] Biochemical and clinical manifestation includes: 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.[15] General symptoms include decreased appetite and growth. Dermatologic symptoms include dermatitis, alopecia (hair loss) and achromotrichia (absence or loss of pigment in the hair).[16] Perosis (a shortening and thickening of bones) is seen in the skeleton. Fatty liver and kidney syndrome (FLKS) and hepatic steatosis also can occur.[12]
Uses
Hair problems
The signs and symptoms of biotin deficiency include hair loss that progresses in severity to include loss of eyelashes and eyebrows in severely deficient subjects. Some shampoos are available that contain biotin, but it is doubtful whether they would have any useful effect, as biotin is not absorbed well through the skin.
Cradle cap (seborrheic dermatitis)
Children with a rare inherited metabolic disorder called phenylketonuria (PKU; in which one is unable to break down the amino acid phenylalanine) often develop skin conditions such as eczema and seborrheic dermatitis in areas of the body other than the scalp. The scaly skin changes that occur in people with PKU may be related to poor ability to use biotin. Increasing dietary biotin has been known to improve seborrheic dermatitis[17] in these cases.
Diabetes
Diabetics may also benefit from biotin supplementation. In both insulin-dependent and non-insulin-dependent diabetes, supplementation with biotin can improve blood sugar control and help lower fasting blood glucose levels, in some studies the reduction in fasting glucose exceeded 50 percent. Biotin can also play a role in preventing the neuropathy often associated with diabetes, reducing both the numbness and tingling associated with poor glucose control.[18][19]
Toxicity
Animal studies have indicated few, if any, effects due to toxic 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, particularly when used in the treatment of metabolic disorders causing sebhorrheic dermatitis in infants.[20]
Laboratory uses
In the laboratory, biotin is often chemically linked to proteins for biochemical assays. Its 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) 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 GuHCl 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 primary antibodies against the antigen of interest, followed by a detection step using streptavidin conjugated to a reporter molecule, such as Horseradish peroxidase.
See also
References
- ^ Merck Index, 11th Edition, 1244.
- ^ Supplementinfo.org
- ^ 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.
{{cite book}}: CS1 maint: multiple names: editors list (link) - ^ National Health and Medical Research Council: Nutrient Reference Values for Australia and New Zealand
- ^ Zempleni J, Wijeratne SS, Hassan YI. (2009). "Biotin". Biofactors. 35 (1): 36–46. doi:10.1002/biof.8. PMID 19319844.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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. doi:10.1006/bmme.1995.1059. PMID 8593541.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Laitinen OH, Hytonen VP, Nordlund HR, Kulomaa MS. (2006). "Genetically engineered avidins and streptavidins". Cell Mol Life Sci. 63 (24): 2992–3017. doi:10.1007/s00018-006-6288-z. PMID 17086379.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Holmberg A, Blomstergren A, Nord O; et al. (2005). "The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures". Electrophoresis. 26 (3): 501–10. doi:10.1002/elps.200410070. PMID 15690449.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Zempleni J, Mock DM. (1999). "Biotin biochemistry and human requirements". J Nutr Biochem. 10 (3): 128–138. doi:10.1016/S0955-2863(98)00095-3. PMID 15539280.
- ^ "Biotin". DSM Nutritional Products. 2009-08-31. Retrieved 2010-02-19. [dead link]
- ^ Gropper S.S., Smith, J.L.,Groff, J.L. (2005). Advanced nutrition and human metabolism. Belmont. ISBN 0534559867.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ a b c d Combs, Gerald F. Jr. (2008). The Vitamins: Fundamental Aspects in Nutrition and Health. San Diego: Elsevier, Inc. ISBN 9780121834937.
- ^ Bowman, BA and Russell, RM., ed. (2006). "Biotin". Present Knowledge in Nutrition, Ninth Edition, Vol 1. Washington, DC: Internation Life Sciences Institute. ISBN 9781578811984.
{{cite book}}: CS1 maint: multiple names: editors list (link) - ^ a b Higdon, Jane (2003). "Biotin". An evidence-based approach to vitamins and minerals. Thieme. ISBN 9781588901248.
- ^ 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. doi:10.1007/BF01800660. PMID 3930841.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ biology-online.org
- ^ Murray, Michael; Pizzorno, Joseph (1997). "Encyclopedia of Natural Medicine" (Revised 2nd Edition) Three Rivers Press. ISBN 0761511571
- ^ Howstuffworks.com
- ^ Oregon State University, Linus Pauling Institute, Micronutrient Research
- ^ Combs, Gerald F. Jr. (1998). The Vitamins: Fundamental Aspects in Nutrition and Health. Ithaca: Elsevier Academic Press. ISBN 0121834921.pg. 360
External links
- Jane Higdon, "Biotin", Micronutrient Information Center, Linus Pauling Institute, Oregon State University
- Clercq, Pierre J. De (1997). "Biotin: A Timeless Challenge for Total Synthesis". Chemical Reviews. 97 (6): 1755–1792. doi:10.1021/cr950073e. PMID 11848892.
- "Biotin". DSM Nutritional Products. 2009-10-29. Retrieved 2010-05-14.