Page - (000060) - in Biomedical Chemistry: Current Trends and Developments

Biotin-dependent enzymes are common in living organisms and are involved in carboxylation reactions. Biotinylation occurs by the addition of a biotin molecule to a specific lysine residue (Fig. 1.1.11). Figure 1.1.11: Biotin and enzyme-bound biotin. The carboxylation catalysed by biotin-dependent enzymes use carbonate (HCO3−) as source of the carboxyl group, ATP to activate it and Mg2+ to decrease the overall negative charge. The mechanism involves a nucleophilic attack of the biotin moiety on the activated carbonate, resulting in the formation of carboxybiotin (Scheme 1.1.45). Nucleophilic attack by the substrate on carboxybiotin results in the transfer of the carboxyl group from biotin to the substrate, as shown in Scheme 1.1.45 with acetyl-CoA. Scheme 1.1.45: Acetyl-CoA carboxylation mechanism. References Allen, K. N., & Dunaway-Mariano, D. (2004). Phosphoryl group transfer: evolution of a catalytic scaffold. Trends in Biochemical Sciences, 29(9), 495–503. Cleland, W., & Hengge, A. (1995). Mechanisms of phosphoryl and acyl transfer. FASEB J, 9(15), 1585–1594.