carboxybiotin

Carboxybiotin is the carboxylated form of biotin, acting as a transient intermediate in the catalytic cycle of biotin-dependent carboxylases. In these enzymes, biotin is covalently linked to a lysine residue on the biotin carboxyl carrier protein (BCCP) or within the enzyme’s biotin carboxylase/transferase framework. Carboxylation of biotin, using ATP and bicarbonate, yields carboxybiotin, which then serves as the carboxyl donor to substrate molecules.

In many biotin-dependent carboxylases, including acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase, the carboxyl group is first introduced onto biotin to form carboxybiotin. A subsequent transferase step relocates the carboxyl group from carboxybiotin to the appropriate substrate, producing the carboxylated product (for example, oxaloacetate from pyruvate or malonyl-CoA from acetyl-CoA) and regenerating free biotin for another cycle.

Biochemically, the process involves a two-step cycle: (1) carboxylation of biotin by biotin carboxylase with bicarbonate and ATP to form carboxybiotin, and (2) transfer of the carboxyl group from carboxybiotin to the substrate by the carboxyltransferase component. The carboxybiotin intermediate is typically bound within the protein complex and is considered labile and tightly regulated within the catalytic cycle.

Carboxybiotin is thus essential for carbon fixation and fatty acid synthesis pathways, linking energy metabolism to the production of four-carbon and larger carboxylated metabolites.