Acetyl-CoA is one of the most “connected" metabolites in biochemistry, appearing in fatty acid oxidation/reduction, pyruvate oxidation, the citric acid cycle, amino acid anabolism/catabolism, ketone body metabolism, steroid/bile acid synthesis, and (by extension from fatty acid metabolism) prostaglandin synthesis. Most of these pathways will be dealt with separately. Here we will cover the last three.
Figure 6.7.1: Pathways for Cholestrol and Ketone Body Synthesis
The pathways for ketone body synthesis and cholesterol biosynthesis overlap at the beginning. Each of these starts by combining two acetyl-CoAs together to make acetoacetyl-CoA. Not coincidentally, that is the next to last product of oxidation of fatty acids with even numbers of carbons. In fact, the enzyme that catalyzes the joining is the same as the one that catalyzes its breakage in fatty acid oxidation – thiolase. Thus, these pathways start by reversing the last step of the last round of fatty acid oxidation. Both pathways also include addition of two more carbons from a third acetyl-CoA to form Hydroxy-Methyl-Glutaryl-CoA, or HMG-CoA, as it is more commonly known. It is at this point that the two pathways diverge.