Biotin - Carboxybiotin
Adequate Intake ?:
CO2 transfer/carboxylation reactions for nutrient metabolism and energy production; gene expression. Dermatitis, hypotonia, nervous system dysfunction, alopecia. Major Food Sources: Liver, soybeans, eggs. AI: 30 mcg
History & Discovery:
Szent-Gyorgyi, a Hungarian Professor in Biochemistry, who isolated Vitamin B6, also isolated Vitamin B7. He found that feeding liver to the animals could prevent "egg white injury". He identified this mysterious substance as "factor X" and called it Vitamin H at first.
"The isolation of biotin as the methyl ester from egg yolk and vitamin H from liver has been described, and the identity of vitamin H and coenzyme R with biotin has been established."
Hungarian scientist Paul Gyorgy began investigating the factor responsible for egg-white injury in 1933 and in 1939, was successful identifying what he called "Vitamin H" (the H represents Haar und Haut, German for 'hair and skin'). Further chemical characterization of vitamin H revealed that it was water-soluble and present in high amounts in the liver. After experiments performed with yeast and Rhizobium trifolii, West and Wilson isolated a compound they called co-enzyme R.
By 1940, it was recognized that all three compounds were identical and were collectively given the name: biotin. Gyorgy continued his work on biotin and in 1941 published a paper demonstrating that egg-white injury was caused by the binding of biotin by avidin.
Avidin is a protein in egg-whites that binds to biotin and their interaction is the strongest non-covalent protein bond known in nature. Heat denatures this protein bond.
Biotin is protein-bound in liver, dairy, meat, fish, eggs, spinach, carrots, cabbage, sweet potato, bananas, avocado, nuts, bananas, berries.
Proteolysis occurs through pepsin and proteasis release in the stomach yielding biotin and byocitin.
The Jejunum is the primary site of absorption. Biocytin is converted with biotinisade into biotin, which is then transported into the enterocytes with the SMVT transporter.
Absorption and Storage:
Nearly 100% absorbed. Stored in small quantities in muscle, liver, and brain.
Free biotin found in blood (80%), with the remainder bound to albumin and globulins.
Uptake into tissues requires SVMT1 with dietary intakes.
Biotin's Main Function:
Co-factor for Carboxylation: Biotin functions in cells as a coenzyme carrier for the transfer of "activated biocarbonate" (HCO3) to substrates in an ATP and magnesium-dependent process. Biotin carries and donates CO2; hence it's role as a co-factor for carboxylation (adding CO2).
Pyruvate carboxylase -> converts pyruvate to oxaloacetate # Replenishes oxaloacetate for TCA cycle, necessary for gluconeogenesis
Acetyl-CoA carboxylase -> forms malonyl-CoA from acetate # Commits acetate units to fatty acid synthesis
Propionyl-CoA carboxxylase -> converts propionyl-CoA to methylmalonyl-CoA # Provides mechanism for metabolism of some amino acids and odd-chain fatty acids
B-methylcrotonyl-CoA carboxylase -> converts B-methylcrotonyl-CoA to B-methylglutaconyl-CoA # Allows catabolism of leucine and certain isoprenoid compounds
Main roles as a carboxylase: Pyruvate loses a hydrogen, but gains one carbon and two oxygen molecules.
When attached to a carboxylase, biotin is called holocarboxylase
Non co-factor Roles: Histones are small proteins that group together and are found bound to DNA for gene expression. Biotinylation of the histones, done through biotinidase, causes the histones to uncoil and thus creates pores through which transcription factors can reach DNA and activate gene promoter sequences.
Deficiency Diseases, Detection, Cures:
Nausea and vomiting and diarrhea
Nervous system - general effects
Lots of raw eggs (more than 15 or 20 a day) - Avidin binds to biotin and needs heat to break down for biotin releasal.
Anticonvulsant anti-seizure meds such as phenobarbital and carbamezepine
Blood levels after 2-4 weeks
Urine better marker: 3-hydroxyisovaleric acid and 3-hydroxygisoveleryl carnitine generated from altered metabolism of b-methylcrotonyl-CoA