Biotin

GABRIELA CAMPOREALE, JANOS ZEMPLENI

Present Knowledge in Nutrition

International Life Sciences Institute

Lugar: Washington DC, USA; Año: 2006; p. 314 - 326

More than 70 years ago, Boas demonstrated the requirement for the water-soluble vitamin biotin in mammals. Biotin was first isolated by Kogl and Tonnies in 1932, its chemical structure was determined by du Vigneaud et al. in 1942, and it was chemically synthesized by Harris et al. in 1943. The route of microbial biosynthesis of biotin, largely elaborated by Eisenberg et al. working with Escherichia coli, is depicted in Figure 1. In this pathway, dethiobiotin is formed from pimelyl-CoA (which can be synthesized from oleic acid) and carbamyl phosphate. Sulfur is incorporated into dethiobiotin in a synthase-dependent step, generating biotin. Early studies of biotin catabolism were primarily conducted using microbes as model organisms. In a series of groundbreaking experiments, McCormick et al. identified two pathways of biotin catabolism. In one pathway, biotin is catabolized by beta-oxidation of the valeric acid side chain. The repeated cleavage of twocarbon units leads to the formation of bisnorbiotin, tetranorbiotin, and related catabolites that are known to result from beta-oxidation of fatty acids.Beta-Ketobiotin and beta-ketobisnorbiotin are unstable and may decarboxylate spontaneously to form bisnorbiotin methyl ketone and tetranorbiotin methyl ketone.After degradation of the valeric acid side chain to one carbon (tetranorbiotin), microorganisms cleave and degrade the heterocyclic ring. In a second pathway of biotin catabolism, the sulfur in the heterocyclic ring is oxidized to produce biotin-l-sulfoxide,biotin-d-sulfoxide, and biotin sulfone. It is likely that sulfur oxidation in the biotin molecule occurs in the smooth endoplasmic reticulum in a reaction that depends on nicotinamide adenine dinucleotide phosphate. Finally, biotin is catabolized by a combination of beta-oxidation and sulfur oxidation, producing compounds such as bisnorbiotin sulfone. Mammals also catabolize biotin by both beta-oxidation and sulfur oxidation, producing bisnorbiotin, biotin-d-sulfoxide, biotin-l-sulfoxide, bisnorbiotin methyl ketone, biotin sulfone, and teranorbiotin-l-sulfoxide. Whether the beta-oxidation of biotin takes place in mitochondria or peroxisomes is uncertain. Degradation of the heterocyclic ring is quantitatively minor in mammals. Biotin catabolites and biotin each account for about half of the total biotinyl compounds in human urine and plasma.