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Statin therapy inhibits Fatty Acid Synthase via dynamic protein modifications

ABSTRACT: Recent discoveries revealed HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. Upon statin treatment, we observed a strong increase in HMG-CoA levels, and only a single protein was modified. Mass spectrometry revealed fatty acid synthase (FAS) was modified on active site residues and, importantly, the modification is located on non-lysine side-chains.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Liver

SUBMITTER: Alec Trub

LAB HEAD: Matthew D Hirschey

PROVIDER: PXD030952 | Pride | 2022-05-20

REPOSITORIES: Pride

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Statin therapy inhibits fatty acid synthase via dynamic protein modifications.

Trub Alec G AG Wagner Gregory R GR Anderson Kristin A KA Crown Scott B SB Zhang Guo-Fang GF Thompson J Will JW Ilkayeva Olga R OR Stevens Robert D RD Grimsrud Paul A PA Kulkarni Rhushikesh A RA Backos Donald S DS Meier Jordan L JL Hirschey Matthew D MD

Nature communications 20220510 1

Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. Upon statin treatment, we ...[more]

PMID: 35538051

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