Acyl-CoA dehydrogenase is an enzyme that catalyzes the first step in fatty acid beta-oxidation, which introduces a double bond between the alpha and beta carbons of acyl-CoA. 

 a) Provide a reasonable mechanism for the conversion catalyzed by Acyl CoA Dehydrogenase. Use B to denote a generic basic residue in the enzyme, and H-B as a generic acidic residue. 

b) Do you expect this reaction to work for this molecule? Why or why not?

SOLUTION:

a) Here is a reasonable mechanism:

Note that the proton adjacent to the carbonyl (called the alpha proton) is the one that gets deprotonated because it’s more acidic. This is because the conjugate base is resonance stabilized by the carbonyl! This explains why a C-H bond of a regular hydrocarbon has a pKa close to 50, while a C-H bond adjacent to a carbonyl has a pKa close to 20!

As an additional exercise, try drawing the structure of FADH2 based on this mechanism! Google the molecule online if you want to check your answer. 

b) NO! There is no longer a carbonyl group, so the conjugate base cannot be stabilized by resonance anymore. Therefore, this specific reaction will not occur, since all the C-H bonds have a pKa close to 50 in this molecule.