The HMG-CoA reductase inhibitory potential of fatty acid amides

Abstract

HMG-CoA reductase (HMGCR) plays a key role as the rate-limiting enzyme in cholesterol biosynthesis. Fatty acid amides possess a range of biochemical and physiological functions. In an attempt to identify potential inhibitors of HMGCR, three fatty acid amides - namely stearamide, oleamide, and butyramide  were investigated. Results demonstrated that these amides inhibited the activity of HMGCR, with stearamide being the most potent, followed by oleamide and butyramide. Stearamide appears to demonstrate a competitive mode of inhibition for HMGCR. Notably, these fatty acid amides interacted with key amino acid residues in the catalytic region of HMGCR through hydrogen bonding and hydrophobic interactions. These findings highlight the necessity for further research to delve into the effects of fatty acid amides on HMGCR inhibition in both in vitro and in vivo.