CHAPTER 10: Biochemistry of Biotin

Biotin serves as a coenzyme for five carboxylases in mammals; the covalent binding of biotin to carboxylases is catalysed by holocarboxylase synthetase (HLCS). Biotin-dependent carboxylases play essential roles in fatty acid synthesis, mitochondrial uptake of fatty acid, gluconeogenesis, metabolism of odd-chain fatty acids and catabolism of leucine. HLCS also catalyses the binding of biotin to histones, thereby mediating gene repression and genome stability. It is unknown whether gene repression and genome stability depend on biotinylation of histones or physical interactions between HLCS and chromatin proteins. In addition to its roles in intermediary metabolism and chromatin biology, biotin modulates cell signals such as cGMP, NF-κB, Sp1 and Sp3, nitric oxide, receptor tyrosine kinases and biotinyl-5′-AMP, thereby altering gene expression. Consistent with the roles of biotin in intermediary metabolism, epigenetics and cell signalling, biotin deficiency has been linked with impaired immune function, birth defects and de-repression of retrotransposons. HLCS knockdown decreases heat survival and life span in Drosophila melanogaster compared with wild-type controls.