Assessing the HMG-CoA reductase inhibitory potential of five fatty acids

Abstract

Fatty acids play a key role as building blocks of lipids. Their lipid-lowering properties have been proven in early biochemical investigations. This investigation focuses on assessing the effects of five fatty acids—including oleic acid, linoleic acid, docosahexaenoic acid (DHA), 5,8,11,14-eicosatetraynoic acid (ETYA), and butyric acid—on the direct inhibition of HMG-CoA reductase (HMGCR), the rate-limiting enzyme involved in cholesterol biosynthesis. To the best of our knowledge, this is the first time that the inhibitory effects of these fatty acids on direct HMGCR activity have been investigated. The fatty acids tested displayed varying levels of HMGCR inhibitory potential, with oleic acid exhibiting the highest efficacy, followed by linoleic acid, DHA, ETYA, and butyric acid. In silico analysis discovered that these fatty acids make hydrophobic interactions and hydrogen bonds with the catalytic domain of HMGCR. This preliminary investigation provides a foundational basis for evaluating the detailed effects of fatty acids as potential treatment options in combination with cholesterol-lowering drugs such as statins.