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Scharnagl, H; März, W; Schliack, M; Löser, R; Gross, W.
A novel assay for cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase activity using reversed-phase ion-pair chromatography: demonstration that Lifibrol (K12.148) modulates the enzyme activity.
J LIPID RES 1995 36: 622-627. Doi: 10.1016/S0022-2275(20)39896-5 [OPEN ACCESS]
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Leading authors Med Uni Graz: Scharnagl Hubert
Co-authors Med Uni Graz: März Winfried
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Abstract:: Cytosolic HMG-CoA synthase and microsomal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase catalyze two sequential steps in the mevalonate pathway. Both enzymes are negatively regulated by cholesterol. Cytosolic HMG-CoA synthase is responsible for the generation of HMG-CoA from acetyl-CoA and acetoacetyl-CoA). We have developed a new method to determine HMG-CoA synthase activity. In this assay, HMG-CoA is formed from acetoacetyl-CoA and labeled acetyl-CoA. The HMG-CoA product is isolated from the reaction mixture by means of reversed-phase ion-pair chromatography. The recovery of the product was always greater than 90%. The average within-batch coefficient of variation for HMG-CoA synthase activity was 5.1%. Using the new assay, we demonstrate that Lifibrol (K12.148), a new hypolipidemic compound, inhibits HMG-CoA synthase. Because our assay is accurate and precise it may become useful in future studies on the regulation and the pharmacological modulation of cytosolic HMG-CoA synthase.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Antilipemic Agents - pharmacology; Butanols - pharmacology; Chickens - pharmacology; Chromatography, Ion Exchange - methods; Cytosol - enzymology; Hydroxybenzoic Acids - pharmacology; Hydroxymethylglutaryl-CoA Synthase - analysis; Liver - enzymology; Research Support, Non-U.S. Gov't - enzymology
Find related publications in this database (Keywords): MEVALONATE PATHWAY; HMG-COA