Biotin

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of biotin
General
Common name
  • Vitamin B 7
  • Vitamin B 8 (France)
  • Vitamin H.
other names
  • (+) - biotin
  • (3a S , 4 S , 6a R ) -Biotin
  • Coenzyme R
  • 5 - [(3a S , 4 S , 6a R ) -2-oxohexahydro-1 H -thieno [3,4- d ] imidazol-4-yl] pentanoic acid
Molecular formula C 10 H 16 N 2 O 3 S
CAS number 58-85-5
ATC code

A11 HA05

Brief description colorless needles
Occurrence Prokaryotes and eukaryotes
physiology
function
Daily need
  • 5–6 μg d −1 (infants)
  • 8–12 μg · d −1 (children up to 8 years)
  • 20–30 μgd −1 (from 9 years)
  • 30–35 μg d −1 (pregnant and breastfeeding women)
Consequences in case of deficiency Inflammation of the skin and tongue, hair loss, anemia, depression, tiredness, fainting, loss of appetite, body aches, high total cholesterol levels, hypoglycaemia
Overdose not known
properties
Molar mass 244.31 g · mol -1
Physical state firmly
Melting point

232-233 ° C

solubility soluble in water (220 mg · l −1 at 25 ° C), in ethanol 96% (800 mg · l −1 at 25 ° C); more soluble in hot water, in dilute alkalis; insoluble in other common organic solvents
safety instructions
Please note the restricted labeling requirements for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Biotin , also known as vitamin B 7 or vitamin H (also vitamin I ), is a water-soluble vitamin from the B complex . As a prosthetic group of enzymes, it plays an important role in the metabolism, but is also important in the cell nucleus for the epigenetic regulation of gene function.

The French nomenclature often names biotin as vitamin B 8 , while “adenylic acid” ( adenosine monophosphate ) is found as vitamin B 8 in Anglo-Saxon and German literature ; Sometimes inositol , which is not a vitamin, or folic acid , which also belongs to the vitamin B complex, is also referred to as vitamin B 8 . However, the name recommended by the IUPAC is only biotin.

history

The substance was discovered in several steps:

  • 1898 - Steinitz - Vitamin H (from H aut)
  • 1901 - Eugene Wildiers and Manile Ide - “Bios”: an aqueous extract from yeast contains a substance that is necessary for yeast to grow
  • 1927 - MA Boas - Description of the "protein injury syndrome", a form of dermatitis : caused by a protein (avidin) contained in egg white, which binds biotin very tightly and reduces its biological availability.
  • 1931 - Paul György - Vitamin H
  • 1936 - Fritz Kögl and Benno Tönnis - First isolation of 1.1 mg biotin from 250 kg dried egg yolk
  • 1940 - György - Finding that biotin is identical to vitamin H and coenzyme R.
  • 1942 - Vincent du Vigneaud - Elucidation of the chemical structure
  • 1943 - Harris et al. - chemical synthesis of biotin

Occurrence and nutrition

Biotin is contained in a great many foods, but mostly only in the single-digit microgram range. The following examples give an overview and relate to 100 g of the food: dry yeast (200 μg), beef liver (103 μg), egg yolk (50 μg), soy (30 μg), oat flakes (20 μg), walnuts (19 μg ), mushrooms (12 ug), paddy rice (12 ug), wheat - whole grain flour (8 ug), fish (7 ug), spinach (6 ug), bovine - and pork (5 ug), bananas (5 ug), Cow's milk (3 μg), apples (1 μg). It has also been described in baker's yeast , wheat bran , peanut butter , porcini mushrooms and liver . It has been known since the 1940s that bacteria contained in the normal intestinal flora produce biotin in addition to other B vitamins and, depending on the type of bacteria and the time available, use it to enrich their environment to varying degrees. One consequence is that the excretions contain more biotin than the food previously consumed. It is very likely that biotin from this source will be used in certain amounts by the organism. However, there is uncertainty about the amount of this contribution.

The German Nutrition Society cites 30–60 μg / day as an estimate for the appropriate intake in healthy adults. In pregnancy and lactation , the same recommendation applies. For infants , the required amount of biotin is assumed to be 5–10 μg / day.

The European RDA states that the desirable intake of biotin for healthy adults is 50 μg / day; a few years ago, 150 μg / day was given.

The exact need is unknown due to the lack of meaningful experimental studies. This makes it necessary to base the information on biotin requirements on plausibility considerations. In the case of infants, for example, the average biotin content of breast milk and the daily amount consumed are used as the basis for the estimate.

Manufacturing

There are numerous multi-step processes for the chemical synthesis of (+) - biotin. In the technically relevant syntheses, fumaric acid , the amino acid ( R ) - cysteine or tetronic acid are used as starting materials. (+) - Biotin is an economically important product in the chemical industry.

properties

The chiral biotin has three stereogenic centers, so that eight stereoisomers are possible. However, only the natural (+) - biotin with (3a S , 4 S , 6a R ) configuration has full biological activity.

physical and chemical properties

Biotin is a substance that crystallizes in colorless needles and is solid at room temperature. The compound does not dissolve very much in cold water, ethanol or dilute acids, but is more soluble in hot water and alkalis . Biotin is insoluble in most organic solvents.

The vitamin is resistant to atmospheric oxygen or elevated temperatures; at 232-233 ° C, biotin melts. Strong bases or acids, oxidizing agents and UV light decompose the compound. Aqueous, neutral solutions of biotin in water are stable up to about 100 ° C. With correct storage and preparation, the losses when cooking vegetable and animal foods are less than 20%.

Physiological and biochemical basics

Biotin metabolism

Biotin is the prosthetic group of several carboxylase enzymes that perform important tasks in protein, fat and carbohydrate metabolism. In order to use the relatively small amounts of biotin contained in food effectively, a recycling mechanism has been developed. The biotin is incorporated into the carboxylases by connecting a special lysine residue of the still inoperable apocarboxylases to a biotin molecule by the enzyme holocarboxylase synthetase , which creates functional holocarboxylases. (See also apo and holoenzymes .) When these biotin-containing carboxylases are broken down again by proteolysis , what remains is biocytin , a combination of biotin and the amino acid lysine. In the next step, biocytin is cleaved by the enzyme biotinidase and biotin is recovered.

However, this biotin cycle is not completely closed, since both biotin and biocytin get into the urine and can be excreted in this way. In addition, the side chain of biotin can fall victim to β-oxidation . The resulting degradation products are not biologically active and are also excreted with the urine. Compensating for these losses is not a problem for healthy people with a normal diet. Since most of the biotin contained in food is not in free form, but rather in protein-bound form, the action of biotinidase is necessary for the release and absorption of biotin even after complete proteolysis of food proteins. In addition, the biotinidase has a storage function within the bloodstream , as it binds biotin to itself to a certain extent and thus protects it from being excreted by the kidneys . Transporter proteins are responsible for the uptake of biotin from the intestine and its transmission into the body tissue , of which only the sodium- dependent multivitamin transporter (SMVT) has been generally identified. If there is a lack of biotin, the increased formation of SMVT can intensify absorption from the intestine and recovery from the kidney tubules. There are indications of the existence of other transporters.

Biotin as a prosthetic group

Biotin is the prosthetic group of carboxylases , more precisely the carboxy transferases . Through their action, carbon dioxide can also be fixed in the animal organism. Examples are:

Pyruvate Carboxylase Reaction

The figure shows the function of biotin as a prosthetic group in the reaction catalyzed by pyruvate carboxylase . Before the addition to the nitrogen of the biotin, the carbon dioxide, which is present as hydrogen carbonate, is converted with ATP into an active form, the carboxyphosphate , a mixed anhydride of phosphoric and carbonic acid. As a prosthetic group, biotin is firmly bound to a lysine residue of the enzyme. The unit (also called biocytin ) acts as a kind of turntable (propeller principle) through which the pyruvate binding site can be operated. The pyruvate is bound there in its enol form , which enables the direct takeover of the CO 2 residue. The reaction exemplifies the use and regeneration of a prosthetic group on one and the same enzyme.

Function in the nucleus

Biotin also plays a role in the cell nucleus , where it can modify histones . It is known that several lysine residues of the histones H2A , H3 and H4 can occur biotinylated. Through this histone modification , biotin has an influence on the structure of the chromatin and the instant readability of the genetic information ( gene silencing ). Biotin is involved in regulating the expression of a large number of genes , probably more than 2000. There is evidence that the enzymes holocarboxylase synthetase and biotinidase can transfer biotin to histones, whereby the biotinidase is probably also able to debiotinylate histones. How these processes work in detail is the subject of current research.

Biotin deficiency

A biotin deficiency affects the carbohydrate , protein and fat metabolism . These consequences result primarily from a functional restriction of the biotin-dependent carboxylases . The clinical picture is therefore generally referred to as multiple carboxylase deficiency . In addition to an actual biotin deficiency, genetic defects in the area of ​​biotin metabolism are also possible triggers.

Symptoms

The following symptoms have been observed in humans as a result of a biotin deficiency: skin disorders , depression , extreme fatigue, drowsiness, muscle pain , hypersensitivity , local abnormal sensations , hallucinations , loss of appetite , nausea , hair loss , color changes in the hair, brittle nails , increased cholesterol levels , abnormally high levels of odd numbers Fatty acids , disorders of the heart function , anemia , gray-pale skin color , movement disorders ( ataxia ), as well as hypotension (low blood pressure), also an increased susceptibility to infections ( candidiasis , keratoconjunctivitis , glossitis ). was ascertained.

Other effects were also found in animals, such as metabolic changes and obesity of the heart muscle, fatty liver , sudden death from hypoglycaemia during exercise, impairment of the immune system and poorer wound healing . In chickens , biotin deficiency significantly reduced the biotin content of the eggs, which led to a reduced hatching rate and frequent malformations of the chicks, although the number of eggs laid remained unchanged. Even in some mammalian species have teratogenic effects of biotin deficiency described.

causes

  • Avidin , one in the egg white contained protein is to bind very tightly able biotin. In addition, avidin is not attacked by digestive enzymes . Heating denatures the avidin and makes it harmless. On the other hand, if the consumption of raw egg white is large enough, all biotin in the intestine can be bound by avidin. This means that both the biotin contained in the food and the biotin formed by the intestinal flora become inaccessible to the organism. As soon as the body's own reserves are exhausted, the symptoms of the biotin deficiency develop. As part of an experiment with volunteers, this started after three to four weeks. In general, this property of avidin is used to generate a biotin deficiency relatively quickly and reliably in humans or animals for experimental purposes.
  • Patients with short bowel syndrome who are dependent on intravenous nutrition develop deficiency symptoms within months or even years if the infusions do not contain biotin. This happens much faster in babies. In addition to shortening the small intestine , damage to the intestinal flora is also one of the risk factors. Long-term use of antibiotics can lead to a biotin deficiency. Chronic alcoholism is also often associated with a depletion of biotin in the body.
  • A biotin deficiency caused solely by a diet low in biotin has hardly been described in humans. An exception were infants who were given a form of ready-to-eat food composed of individual nutrients that did not contain biotin for a long time. In the case of some animals such as chickens or turkeys, however , a biotin deficiency can relatively easily occur due to feed that is poor in biotin.
  • Biotin deficiency was found in some kidney patients who had to undergo dialysis treatment for a long time .
  • Anticonvulsants seem to influence the biotin balance, so that a more or less severe biotin deficiency is expressed.
  • During pregnancy, about a third of women have biochemical changes that indicate a slight biotin deficiency. This usually does not result in any external symptoms. It is believed that biotin is broken down more quickly during pregnancy, since less biotin but higher concentrations of its metabolites are measured in the urine of pregnant women .

Overdose

So far, no harmful effects of biotin have appeared in humans. Everything indicates that the therapeutic breadth is very large. In patients with various disorders of the biotin metabolism, there have been long-term observations on the intake of up to 10 mg biotin per kilogram body weight per day. No negative effects of the high biotin dose were observed. However, some of the patients show irreversible damage because the treatment with biotin started too late . The transfer of such results from metabolic patients to healthy people is of course not easily possible.

Due to the inadequate data situation, no LOAEL value has so far been given officially . (This is the lowest dose that can cause adverse effects.) Few studies have been carried out on animals that have received amounts of biotin large enough to cause adverse effects. For example, in a test lasting several weeks on young rats, it was found that a daily dose of biotin of approximately 80 mg per kilogram of body weight adversely affected their feed intake and growth, which was further increased as the dose continued to rise. Converted to an average weight of 65 kg, this would result in a daily intake of more than 5 g biotin, which corresponds to 100,000 times the physiological requirement.

Although biotin was tolerated by rats in 5,000 to 10,000 times the normal dose without impairment, in pregnant female rats after injections of more than 1 mg biotin per kilogram body weight, resorption by fetuses , combined with impaired estrogen formation, occurred.

Biotin can falsify laboratory values ​​that are determined using immunological methods based on the biotin-streptavidin interaction. Depending on the test setup, false high or false low results can occur. These disorders can occur even with normal biotin dosages.

use

Biotin as a drug

Biotin preparations are used for the treatment and prophylaxis of a biotin deficiency. For prophylaxis, 0.2 mg / day is sufficient. In order to safely compensate for an existing deficiency within a short time, however, a significantly higher dose may be required. Biotin is often part of the multivitamin preparations that are added to infusion solutions when patients have to be fed parenterally over a long period of time, i.e. bypassing the gastrointestinal tract .

Lifelong treatment with very high doses of biotin is the common and extremely effective therapy for the following rare, genetic metabolic diseases :

Biotin is currently being tested in high doses under the name MD1003 against progressive multiple sclerosis in pilot studies.

Biotin in molecular biotechnology

Biotin can be used to label various molecules ( biotinylation ). The interaction between biotin and avidin or streptavidin is used for detection .

See also

Web links

Wiktionary: Biotin  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ^ A b c The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .
  2. ^ David E. Metzler, Carol M. Metzler: Biochemistry: The Chemical Reactions of Living Cells, Volume 1. ISBN 978-0-080-92470-0 , 2001, p. 724.
  3. ↑ a b c d e f Entry on biotin. In: Römpp Online . Georg Thieme Verlag, accessed on April 25, 2012.
  4. ↑ a b Data sheet Biotin, ≥99% (TLC), lyophilized powder from Sigma-Aldrich , accessed on March 16, 2013 ( PDF ).
  5. ↑ a b Y. I. Hassan, J. Zempleni: Epigenetic regulation of chromatin structure and gene function by biotin. In: J. Nutr. 136 (7); 2006 Jul: pp. 1763-5 PMID 16772434 (free full text access ).
  6. ↑ a b Matthias Weider: Identification of cis and trans components of biotin-dependent transcription regulation in Saccharomyces cerevisiae. (PDF; 17.26 MB) Dissertation at the Friedrich-Alexander-University Erlangen-Nürnberg , 2006.
  7. ↑ Steinitz, Franz: About the behavior of phosphorus-containing protein bodies in the metabolism . In: Arch Ges Physiol . 72, 1898, pp. 75-104. doi : 10.1007 / BF01662124 .
  8. ↑ Harris, JA; Wolf, DE; Mozingo, R .; Folkers, K .: Synthetic biotin . In: Science . 97, 1943, p. 447. doi : 10.1126 / science.97.2524.447 .
  9. ↑ Nutrient database of the University of Hohenheim (accessed on October 31, 2009).
  10. ^ PR Burkholder, I. McVeigh: Synthesis of Vitamins by Intestinal Bacteria. In: Proceedings of the National Academy of Sciences . Volume 28, Number 7, July 1942, pp. 285-289, PMID 16578052 , PMC 1078469 (free full text).
  11. ↑ a b c K. S. Roth: Biotin in clinical medicine - a review. In: The American journal of clinical nutrition. Volume 34, Number 9, September 1981, pp. 1967-1974, PMID 6116428 (Review).
  12. ↑ a b H. M. Said: Biotin: the forgotten vitamin. In: The American journal of clinical nutrition. Volume 75, Number 2, February 2002, pp. 179-180, PMID 11815306 (review).
  13. ↑ Reference values for nutrient intake at the DGE (as of 2008). Table for biotin (accessed November 1, 2009).
  14. ↑ Directive 2008/285 / EC (PDF) of the Commission of October 28, 2008 amending Directive 90/496 / EEC (PDF) of the Council on the nutritional labeling of foods with regard to the recommended daily allowances, the conversion factors for the energy value and the definitions.
  15. ↑ a b c d e f g h i K. Pietrzik, I. Golly, D. Loew: Handbuch Vitamins. Urban & Fischer Verlag, Elsevier GmbH, Munich 2008; Pp. 147-154, 416; ISBN 978-3-437-55361-5
  16. ↑ a b c d e f g D. M. Mock: Biotin In: J. Zempleni, RB Rucker, DB McCormick, JW Suttie (Editors): Handbook of Vitamins. 4th edition. CRC Press, 2007; Pp. 361-384; ISBN 0-8493-4022-5 .
  17. ↑ Bernd Schäfer: Natural substances of the chemical industry , Elsevier GmbH, Spektrum Verlag, 2007, pages 455-465, ISBN 978-3-8274-1614-8 .
  18. ↑ Bernd Schäfer: Natural substances of the chemical industry , Elsevier GmbH, Spektrum Verlag, 2007, p. 449, ISBN 978-3-8274-1614-8 .
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  20. ↑ a b c E. R. Baumgartner, T. Suormala: Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. In: International journal for vitamin and nutrition research. Volume 67, Number 5, 1997, pp. 377-384, PMID 9350481 (review).
  21. ↑ a b D. Balnave: Clinical symptoms of biotin deficiency in animals. In: The American journal of clinical nutrition. Volume 30, Number 9, September 1977, pp. 1408-1413, PMID 143210 (review).
  22. ↑ a b A. Taniguchi, T. Watanabe: Roles of biotin in growing ovarian follicles and embryonic development in domestic fowl. In: Journal of nutritional science and vitaminology. Volume 53, Number 6, December 2007, pp. 457-463, PMID 18202531 (review).
  23. ^ A b P.T. Ozand, GG Gascon, M. Al Essa, S. Joshi, E. Al Jishi, S. Bakheet, J. Al Watban, MZ Al-Kawi, O. Dabbagh: Biotin-responsive basal ganglia disease: a novel entity. In: Brain: a journal of neurology. Volume 121 (Pt 7), July 1998, pp. 1267-1279, PMID 9679779 .
  24. ↑ Compilation of tolerable upper intake quantities for macro and micronutrients (status: March 2006; accessed: August 2009) at the DGE . (PDF, 608 kB)
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  26. ↑ Health trap "Vitamin H" [1]
  27. ↑ Guideline Parenteral Nutrition of the DGEM , Chapter 7: Water, electrolytes, vitamins and trace elements (PDF, 139 kB) ( Memento of July 10, 2007 in the Internet Archive ); Printed: HK Biesalski, SC Bischoff, H.-J. Böhles, A. Mühlhofer: 7 Water, electrolytes, vitamins and trace elements. In: Current. Nutritional med. 32 (Suppl. 1); May 2007: pp. S30-S34.
  28. ↑ A. Tourbah, C. Lebrun-Frenay et al. a .: MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomized, double-blind, placebo-controlled study. In: Multiple sclerosis. Volume 22, number 13, November 2016, pp. 1719–1731, doi : 10.1177 / 1352458516667568 , PMID 27589059 , PMC 5098693 (free full text).
  29. ↑ Thomas Boenisch (editor): Handbook of Immunochemical Staining Methods, 3rd edition 2003, DakoCytomation GmbH, Hamburg, Germany.