Molecular genetics of biotin metabolism: old vitamin, new science.
Biotin is a water-soluble vitamin that participates as a cofactor in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. It functions as the carboxyl carrier for biotin-dependent carboxylases. Its covalent attachment to carboxylases is catalyzed by holocarboxylase synthetase. Our interest in biotin has been through the genetic disease, "biotin-responsive multiple carboxylase deficiency," caused by deficient activity of holocarboxylase synthetase. As part of these studies, we made the unexpected findings that the enzyme also targets to the nucleus and that it catalyzes the attachment of biotin to histones. We found that patients with holocarboxylase synthetase deficiency have a much reduced level of biotinylated histones, yet the importance of this process is unknown. The dual nature of biotin, as the carboxyl-carrier cofactor of carboxylases and as a ligand of unknown function attached to histones, is an enigma that suggests a much more involved role for biotin than anticipated. It may change our outlook on the optimal nutritional intake of biotin and its importance in biological processes such as development, cellular homeostasis and regulation.
Gravel
Roy A
RA
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1. rgravel@ucalgary.ca
Narang
Monica A
MA
D000818:Animals; D001710:Biotin / Q000378:metabolism*; D043523:Biotinidase / Q000235:genetics / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D029968:Escherichia coli Proteins; D006657:Histones; D012097:Repressor Proteins; D014157:Transcription Factors; D001710:Biotin; D043523:Biotinidase; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases; C058125:birA protein, E coli