HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGR) catalyzes the committed step in cholesterol biosynthesis. Statins are HMGR inhibitors with inhibition constant values in the nanomolar range that effectively lower serum cholesterol levels and are widely prescribed in the treatment of hypercholesterolemia. We have determined structures of the catalytic portion of human HMGR comple...

In the preceding paper evidence was presented for the biosynthesis of lysophosphatidic acid from monoglyceride and adenosine triphosphate (1). Exogenous monoglycende was found to stim.ulate the formation of phosphatidic acid as well as lysophosphatidic acid. This observation suggested that lysophosphatidic acid was being converted to phosphatidic acid and therefore was functioning as an interme...

Megraw, Robert E. (Albert Einstein Medical Center, Philadelphia, Pa.), Henry C. Reeves, and Samuel J. Ajl. Formation of lactyl-coenzyme A and pyruvyl-coenzyme A from lactic acid by Escherichia coli. J. Bacteriol. 90:984-988. 1965.-Cell extracts of propionate-adapted Escherichia coli were found to contain a lactyl-coenzyme A (CoA) synthetase which catalyzes the formation of the CoA thiolester fr...

A patient with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase, EC 4.1.3.4) deficiency presented consistently above-normal values of plasma amylase (EC 3.2.1.1). Activities measured were in the lower normal range in family members not proven heterozygotes and in the upper normal range in the proven heterozygotes. Heterozygosity was proven by intermediate HMG-CoA lyase activities determined ...

Results from large-scale clinical trials of lipid lowering with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have led to a revolution in the management of atherosclerosis. In addition to their potent effect on serum lipid levels, statins influence several other cellular pathways, including those involving inflammatory, oxidative, and thrombotic processes. These...

OBJECTIVE A recent study identified a new class of compounds designated as the sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) ligands that putatively bind to SCAP, leading to increased LDL receptor (LDLR) expression. In this study, we examined the effects of SCAP ligand GW707 in comparison with lovastatin and cytokine oncostatin M (OM) on the regulation of ...

Stearoyl-coenzyme A desaturase (SCD) is a key regulator of membrane fluidity, turns over rapidly, and represents a prototype for selective degradation of resident proteins of the endoplasmic reticulum. Using detergent-solubilized, desaturase-induced rat liver microsomes we have characterized a protease that degrades SCD. Degradation of SCD in vitro is highly selective, has a half-life of 3-4 h,...

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5) was purified to homogeneity from ox liver and obtained essentially free from acetoacetyl-CoA thiolase activity. The purification procedure included substrate elution from cellulose phosphate and chromatofocusing. The relative molecular mas was about 100 000 and S20,w0 was 6.36S. The enzyme appears to be a dimer of identical subu...

In addition to lowering low-density lipoprotein cholesterol, statins improve vascular function by cholesterol-independent effects in experimental models. These extrahepatic effects are often called “pleiotropic”; however, specific underlying molecular mechanisms have been identified in animal and cell culture studies. They relate to the inhibition of isoprenylation of small G proteins. Inhibiti...

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the ileum of rats was inactivated by Mg2+-ATP and reversibly reactivated by cytoplasmic activator from the liver. The mevalonate kinase reaction was presumably not involved in this inactivation. Studies of nucleotide specificity for the inactivation revealed that ATP was most effective in the reaction among the nucleotides tested. In ...