RT Book, Section A1 Craigen, William J. A1 Kozicz, Eva Morava A2 Kline, Mark W. SR Print(0) ID 1182928883 T1 Biotin Responsive Disorders T2 Rudolph's Pediatrics, 23e YR 2018 FD 2018 PB McGraw-Hill Education PP New York, NY SN 9781259588594 LK accesspediatrics.mhmedical.com/content.aspx?aid=1182928883 RD 2024/03/28 AB Biotin (vitamin B7 or vitamin H) is a water-soluble vitamin that functions as a carboxyl carrier in carboxylation, decarboxylation, and transcarboxylation reactions, and is attached to a lysine residue in a highly conserved domain common to all biotin-dependent carboxylases. The 5 biotin-dependent carboxylases in humans are mitochondrial propionyl-coenzyme A (CoA), β-methylcrotonyl-CoA, pyruvate carboxylases, and mitochondrial and cytosolic forms of acetyl-CoA carboxylase, with each carboxylase having specific roles in fatty acid, glucose, and amino acid metabolism. Biotin is covalently attached to carboxylases by the enzyme holocarboxylase synthetase (HLCS) encoded by the HLCS gene, while biotinidase, encoded by the BTD gene, provides free biotin following proteolysis of the carboxylase protein. Hence, biotinidase deficiency (Mendelian Inheritance in Man [MIM] no. 253260) reflects an inability to hydrolyze biocytin (biotinyllysine) or small biotin-containing peptide fragments from carboxylases, leading to a lack of free biotin, while holocarboxylase synthetase deficiency (MIM no. 253270) reflects a failure to incorporate biotin into the apoenzymes. The activity of HLCS involves a 2-step, adenosine triphosphate (ATP)-dependent reaction in which biotin is first activated to biotinyl-5’-adenosine monophosphate (AMP) and then transferred to the apocarboxylase substrate, with release of AMP. Failure to attach or recycle biotin leads to significantly reduced activity of these biotin-dependent carboxylases and results in multiple carboxylase deficiency. Humans cannot synthesize biotin, and they obtain it from exogenous sources via intestinal absorption. Absorption of biotin and transport of the vitamin into a variety of cell types occurs via a saturable, Na+-dependent, carrier-mediated mechanism that involves the human sodium-dependent multivitamin transporter, hSMVT, encoded by the SLC5A6 gene, which has been shown to also transport pantothenate and lipoate.