Using your knowledge of fatty acid biosynthesis, provide an explanation for the following experimental observations:
(a) The addition of uniformly labeled [14C] acetyl-CoA to a soluble liver fraction yields palmitate uniformly labeled with 14C.
(b) However, the addition of a trace of uniformly labeled [14C]acetyl-CoA in the presence of an excess of unlabelled malonyl-CoA to a soluble liver fraction yields palmitate labeled with 14C only in C-15 and C-16.
How does fatty acid biosynthesis proceed?
Acetyl-CoA is used to form malonyl-CoA with the help of acetyl-CoA carboxylase and CO2. This is an important key in the process. Once malonyl-CoA is formed, the malonyl group is transferred to the fatty acid synthase as malonyl-ACP. Likewise, the acetyl group from acetyl-CoA is transferred to the enzyme as acetyl-ACP. These two activated groups react via the 3-ketoacyl synthase to form acetoacetyl-ACP. This acetoacetyl-ACP complex is reduced (forming the alcohol), then dehydrated (with the loss of H2O) forming the double bond, then reduced again forming the butyryl-ACP complex.
This cycle is now repeated and the chain grows by two carbons each round.
Now, where are the two carbons from the malonyl unit in the first condensation? The two carbons from malonyl unit are the two carbons nearest the ACP group. Or, ...
This solution give detailed explanations for two given experimental observations, addressing soluble liver fractions yield and malonyl-CoA