Fig. 5.
CoA thioesters of ketone bodies are not plausible inhibitors of HMGCR. (A) Structure of the HMGCR substrate 3-hydroxy-3-methylglutaryl coenzyme A, the ketone bodies β-hydroxybutyrate and acetoacetate, and four statin inhibitors of HMGCR. The seemingly common pharmacophore is highlighted in red. (B) Michaelis-Menten kinetic analysis of human HMGCR activity with the indicated test inhibitors suggests that neither is physiologically likely: the Ki for both is much higher than the KM for the substrate.