Inactivation of 3-hydroxy-3-methylglutaryl coenzyme a reductase in cultured human blood mononuclear cells by procetofenic acid

Claudio Massaroli, Domenico Sommariva, Umberto Bortolini, Claudio Paolino, Angelo Fasoli, C Massaroli, D Sommariva, U Bortolini, C Paolino, A Fasoli

Index: Pharmacol. Res. Commun. 14(1) , 51-60, (1982)

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Abstract

The effect of procetofenic acid on 3-hydroxy-3-methylglutaryl Coenzyme A reductase (HMG-CoA reductase) activity has been studied on cultured human blood mononuclear cells. The drug produced a sharp decrease in enzyme activity both when it was added to the incubation medium and when it was added to the HMG-CoA reductase assay mixture. These findings strongly suggest that procetofenic acid inhibits HMG-CoA reductase activity by inactivating enzyme protein or by interfering with enzyme-substrate interaction. Since HMG-CoA reductase is a rate-limiting enzyme in cholesterol biosynthesis, its inhibition may explain, at least in part, the hypocholesterolemic effect of the drug.