Regulation of early cholesterol biosynthesis in rat liver: effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
A HondaS Shefer

Abstract

Cytosolic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase catalyzes the formation of HMG-CoA, the substrate for the rate-controlling enzyme in the cholesterol biosynthetic pathway. To explore the regulation in liver, we developed a new, accurate, and reliable reversed-phase ion-pair chromatographic assay that uses nonradioactive substrates and n-propionyl coenzyme A as an internal recovery standard. The hepatic activities were measured in rats treated with cholesterol, sitosterol, cholic acid, deoxycholic acid, ursodeoxycholic acid, cholestyramine, bile fistula, lovastatin, and BM 15.766, an inhibitor of 7-dehydrocholesterol delta7-reductase, and were compared with microsomal HMG-CoA reductase and cytosolic acetoacetyl coenzyme A (AcAc-CoA) thiolase activities. HMG-CoA synthase activity was effectively suppressed in synchrony with HMG-CoA reductase activity by treatments with cholesterol (-41%, P < .05), cholic acid (-72%, P < .005), and deoxycholic acid (-62%, P < .05). However, ursodeoxycholic acid increased activity 84% (P < .05) and intravenous sitosterol did not change activity. AcAc-CoA thiolase activities also paralleled HMG-CoA reductase and HMG-CoA synthase activities, but differences were not statistically si...Continue Reading

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Citations

Oct 7, 2006·Current Opinion in Gastroenterology·S J Karpen, J M Crawford
May 12, 2009·The Journal of Steroid Biochemistry and Molecular Biology·Enrique ViturroHeinrich H D Meyer
Dec 29, 2004·FEMS Microbiology Letters·Hassan HajjajPeter Niederberger
Apr 13, 2007·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Rainie L Sharpe, Deborah L MacLatchy
Jan 13, 2021·Neurobiology of Disease·Alireza P ShabanzadehPhilippe P Monnier

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