# 10.8: Biotin

The 2 primary dietary forms of biotin are free biotin and biocytin (aka biotinyllysine)1. The structure of biotin is shown below.

Biocytin is biotin bound to the amino acid lysine as seen in its structure below.

Free biotin is believed to be highly absorbed. Before uptake, biocytin is acted on by the enzyme biotinidase, forming free biotin and lysine. Free biotin is then taken up into the enterocyte through the sodium-dependent multivitamin transporter (SMVT), as shown below1,4,5.

Most biotin is excreted in the urine.

## Biotin Functions

Biotin is an important cofactor for carboxylase enzymes. As the name sounds, these enzymes add carboxylic acid groups ($$\ce{-COOH}$$) to whatever compound they act on. In fatty acid synthesis, biotin is required by the enzyme that forms malonyl-$$\ce{CoA}$$ from acetyl-$$\ce{CoA}$$, as shown below1.

Another biotin-requiring carboxylase is one that converts pyruvate to oxaloacetate in gluconeogenesis as shown below1.

In addition to these two functions, biotin is also important for histone biotinylation and the breakdown of isoleucine, leucine, methionine, and threonine1.

Histone biotinylation is an epigenetic modification that is described in the next section.

Biotin is an effective treatment for brittle nail syndrome, but it has not been shown to improve healthy nails8. There is little evidence to suggest that biotin improves healthy hair as well9.

## Epigenetics

What is epigenetics? Epigenetics means "above the genome." To use a computer analogy, if the DNA sequence is the hardware, epigenetics can be viewed as the software. The nucleotide sequence of the human genome is known, and there is surprisingly little difference between individuals. However, the 2 main epigenetic modifications play a major role in determining what genes are expressed:

• DNA methylation
• Histone modification

These epigenetic modifications are illustrated in the following figure.

DNA methylation is the addition of a methyl group to a DNA base, which decreases gene transcription. Conversely, demethylation increases gene transcription.

DNA does not exist simply as long double strands, instead it is packaged and shaped so that it can fit in the nucleus of our cells. The first part of this packaging is that DNA is wrapped around proteins called histones as shown below.

Histone modification occurs when there are additions or subtractions to the histones themselves. The most common is acetylation (addition of an acetyl group) or deacetylation of histones. The structure of acetyl is shown below.

Histone acetylation causes the DNA structure to open up so that transcription can occur. Histone deacetylation causes the DNA to become more tightly packed, preventing transcription from occurring.

Together, these modifications to DNA and histones are known as the epigenetic code. The following two videos do a good job explaining epigenetics and tying together its two different methods of modification. The Tale of 2 Mice describes how great an impact that the methylation status (whether it is methylated or unmethylated) of the agouti gene has on physical characteristics of genetically identical mice. The second video illustrates how histone modifications impact gene transcription.

How does this relate to biotin? Histones can be biotinylated, or have biotin added to the histone. However, it should be noted that histone biotinylation is rare (<0.001% of human histones H3 and H4), so it is questionable how much impact this action has13.

## Biotin Deficiency & Toxicity

Biotin deficiency is very rare. Symptoms of biotin deficiency include14:

• Skin rash
• Hair loss
• Neurological Impairments

There are a couple of ways that a person could develop a deficiency in biotin. First, a very small number of people are born with a mutation in biotinidase that results in them not being able to cleave biocytin for absorption1. Another way is through the consumption of raw eggs. Drinking raw eggs is not something that most people do. However, some people do it to imitate Sylvester Stallone's movie character Rocky, who consumed them as part of his boxing training regimen. If you are not familiar with this movie the link below shows you how Rocky consumed his raw eggs.

The potential problem with consuming raw eggs routinely is that raw egg whites contain a protein called avidin which binds biotin and prevents its absorption. However, it would take more than two dozen egg whites consumed daily over many months to cause a deficiency, making this an unlikely occurrence15. Cooking denatures avidin and prevents it from binding biotin, meaning that cooked eggs are not a concern.

No toxicity of biotin has been reported.

## References

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
2. en.Wikipedia.org/wiki/File:Bi..._structure.svg
3. commons.wikimedia.org/wiki/File:Biocytin.svg
4. Said H, Mohammed Z. (2006) Intestinal absorption of water-soluble vitamins: An update. Curr Opin Gastroenterol 22(2): 140-146.
5. Zempleni J, Wijeratne SSK, Hassan Y. (2009) Biotin. Biofactors 35(1): 36-46.
6. en.Wikipedia.org/wiki/File:An...%28edit%29.svg
7. en.Wikipedia.org/wiki/File:CellRespiration.svg
8. Scheinfeld N, Dahdah MJ, Scher R. (2007) Vitamins and minerals: their role in nail health and disease. 6(8): 782-787.
9. Famenini S, Goh C. (2014) Evidence for supplemental treatments in androgenetic alopecia. 13(7): 809-812.
10. https://en.Wikipedia.org/wiki/Epigen...mechanisms.jpg
11. en.Wikipedia.org/wiki/File:Nu..._structure.png
12. en.Wikipedia.org/wiki/File:Acetyl.svg
13. Kuroshi T, Rios-Avila L, Pestinger V, Wijeratne SSK, Zempleni J. (2011) Biotinylation is a natural, albeit rare, modification of human histones. Mol Genet Metab, 104, 537-545.
14. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw's perspectives in nutrition. New York, NY: McGraw-Hill.
15. Whitney E, Rolfes SR. (2008) Understanding nutrition. Belmont, CA: Thomson Wadsworth.