Biotin Metabolism in M. musculus
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Biotin Metabolism in M. musculus

Biotin is a water-soluble vitamin found in all organisms that functions as a cofactor of Biotin-dependent carboxylases. It belongs to the B-Complex group of Vitamins and is an essential micronutrient for all mammals. The role of Biotin (or Vitamin-H) in Carboxylases is to act as vector for carboxyl-group transfer between donor and acceptor molecules during Carboxylation reaction (Ref.1). In M. musculus (Mus musculus), Biotin is a covalently bound as a prosthetic group in Biotin-dependent Carboxylases. It is covalently attached to Carboxylases by the action of Biotin-Protein Ligase. As a co-factor Biotin changes Apocarboxylases into active Holocarboxylases. For Biotin-Protein Ligase, Biotin addition occurs as an ATP-dependent, two-step reaction that, in the first step, involves synthesis of the intermediate, Biotinyl-5-AMP. In the second step, Biotinyl-5-AMP is used to transfer Biotin, with release of AMP, to a specific Lysine residue in a highly conserved region in Apocarboxylases. Biotin enters into to the body through food and is also synthesized by the normal microflora present in the murine intestine, where it is partly absorbed by colonocytes (Ref.1 & 2).

Biotin is present in very low concentrations in nature, thus putting the metabolic homeostasis of the cell at risk. Unlike Bacteria, higher organisms are unable to synthesize Biotin and thus depend entirely on the Vitamins present in foods to satisfy their Vitamin requirements. To deal with their Biotin requirements, higher organisms have evolved to a very efficient and complex Biotin cycle to ensure adequate supply and utilization of the Vitamin (Ref.2 & 3). Most Biotin present in foods is not readily available because it is protein-bound and must be released from the Holocarboxylases to which it is attached before it can be used in Carboxylation reactions. This reaction is carried out by Peptide Hydrolases and pancreatic Btd (Biotinidase), which specifically cleaves the quasi-peptide bond between Biotin and Epsilon-amino group of L-Lysine residue to which it is attached in the Biocytin (Biotin-Lysine) complex. Biotin released in intestinal lumen is actively absorbed in a sodium-dependent fashion across the brush-border membrane of enterocytes. Once inside the cell, Biotin is again covalently attached to Apocarboxylases by Biotin-Protein Ligase and the cycle continues. L-Lysine is further subjected to degradation. During turnover of Carboxylases, Biotinylated peptides are then cleaved by cytoplasmic or plasma Btd thus allowing Biotin to be recycled and used in Biotinylation of new carboxylases. The importance of this cycle in maintaining Biotin levels within the cell is evidenced by the fact that mutations in either Btd or Peptide Hydrolases results in a potentially lethal metabolism disorder. Biotin may also play a role in other cellular events in eukaryotic organisms such as transcriptional or translational regulation or enhancement of activity of different Hepatic enzymes. In these studies, Biotin appears to augment Glucokinase enzymatic activity and transcription of its gene. It is proposed that Biotin has different roles in the cell that vary from those of its function as carboxylase cofactor (Ref.3 & 4).