Using directed evolution, we have selected an adipyl acylase enzyme that can be used for a one-step bioconversion of adipyl-7-aminodesacetoxycephalosporanic acid (adipyl-7-ADCA) to 7-ADCA, an important compound for the synthesis of semisynthetic cephalosporins. The starting point for the directed evolution was the glutaryl acylase from Pseudomonas SY-77. The gene fragment encoding the beta-subu...

Inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase have been approved for treatment of hypercholesterolemia in humans. This class of therapeutic agents, in addition to lowering plasma cholesterol, reduces plasma triglyceride levels. We have investigated the mechanism of triglyceride-lowering effect of lovastatin in the hypertriglyceridemic state by using a rodent model of ...

3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Several large landmark clinical studies have shown a marked reduction of cardiovascular mortality and morbidity in patients treated with statins. Because of the strong association between serum cholesterol levels and coronary artery diseas...

BACKGROUND 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have several pleiotropic effects, including anti-inflammatory properties, and are reported to improve endothelial functions. Pathophysiologically, acute lung injury (ALI) is caused by a severe inflammatory response and endothelial dysfunction. OBJECTIVE To investigate the effects of simvastatin (an HMG-CoA reduct...

The clinical benefits of statins are strongly related to their low density lipoprotein-cholesterol (LDL-C) lowering properties. However, because mevalonic acid (MVA), the product of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase reaction, is the precursor not only of cholesterol but also of nonsteroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may result in pleiot...

RATIONALE Human atherosclerotic plaques contain large numbers of cells deprived of O(2). In murine atherosclerosis, because the plaques are small, it is controversial whether hypoxia can occur. OBJECTIVE To examine if murine plaques contain hypoxic cells, and whether hypoxia regulates changes in cellular lipid metabolism and gene expression in macrophages. METHODS AND RESULTS Aortic plaques...

BACKGROUND Polycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, hyperplastic theca compartment and increased androgen production due to, at least in part, excessive expression of several key genes involved in steroidogenesis. Previously, our group has demonstrated that simvastatin, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a rat...

Coenzyme Q10 (CoQ10) deficiency has been proposed to be causal in 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor (statin)-induced myopathies. However, the clinical benefit of supplementation is unproved. The purpose of the present study was to assess the effect of CoQ10 supplementation on myalgias presumed to be caused by statins. Patients currently receiving a statin who developed ...