In humans, vitamin B7 (biotin) is a covalently bound cofactor (“prosthetic group”) attached at the active site of five enzymes known as ‘carboxylases’ (3). The attachment of biotin to another molecule, such as a protein (e.g. histone), is known as ‘biotinylation’. The holocarboxylase synthetase (HCS) catalyses the post-translational biotinylation of the apocarboxylases, thus converting them into biological active holocarboxylases (45). The release of biotin from peptide products after the breakdown of biotinylated proteins is catalysed by the enzyme biotinidase (45). In mammals, five biotin-dependent carboxylases exist: acetyl-Coenzyme A (CoA) carboxylase 1 (ACC1) and acetyl-CoA carboxylase 2 (ACC2), pyruvate carboxylase (PC), methylcrotonyl-CoA carboxylase (MCC), and propionyl-CoA carboxylase (PCC) (45, 46).
Each carboxylase catalyzes an essential metabolic reaction required for the synthesis of fatty acids (ACC1 & 2), the formation of glucose from sources other than carbohydrates (e.g., amino acids; PC), the catabolism of leucine (an essential amino acid), and the metabolism of certain amino acids, cholesterol and certain fatty acids (PCC) (4, 46).
Evidence indicates that biotinylation of histones in the eukaryotic nuclei plays a role in regulating DNA replication , genome stability (59) (chromatin structure) and gene expression (‘transcription’) of proteins involved in biotin and intermediary metabolism (60) as well as cell division (‘proliferation’) (61) and other cellular responses (5, 6, 7, 45, 58).
The European Food Safety Authority (EFSA), which provides scientific advice to assist policy makers, has confirmed that clear health benefits have been established for the dietary intake of biotin in contributing to:
