Page - (000050) - in Biomedical Chemistry: Current Trends and Developments

2. The diphosphate group leaves, resulting in an activated acid in the form of a mixed anhydride (acyl AMP). (PPi is a good leaving group as it is stable and not nucleophilic) 3. Another acyl substitution is performed on the mixed anhydride by the thiol moiety in CoA (a moderate nucleophile). Again, this is facilitated because AMP is a good leaving group. Scheme 1.1.37: Activation of a fatty acid via esterification. With the thioester (activated fatty acid) formed, β-oxidation may now occur through a sequence of dehydrogenation, hydration and dehydrogenation reactions: 1. The Cα-Cβ single bond is oxidised to a double bond, with flavin adenine nucleotide (FAD) as the oxidant. This step occurs in a family of acyl-CoA dehydrogenases where the products are FADH2 (reduced FAD) and α,β-unsaturated acyl-CoA. The mechanistic details of this step are not yet fully resolved, though it is known that one of the α protons may be first attacked by 376-Glu and a β-hydride is abstracted from the fatty acid by FAD.