Mechanism of synthesis of citryl CoA by citrate synthase. (1) In the substrate complex (left), His 274 donates a proton to the carbonyl oxygen of acetyl CoA to promote the removal of a methyl proton by Asp 375 to form the enol intermediate (center). (2) Oxaloacetate is activated by the transfer of a proton from His 320 to its carbonyl carbon atom. (3) Simultaneously, the enol of acetyl CoA attacks the carbonyl carbon of oxaloacetate to form a carbon–