Simvastatin (SIM) (Figure 1) reduces levels of circulating atherogenic lipoproteins by competitive inhibition of the microsomal enzyme 3-hydroxy-3-methylglutaryl-co-enzyme A(HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, a critical intermediary in the biosynthesis pathway of cholesterol1. Also SIM inhibits oxidation of native and modified low-density and high-densi...

To elucidate the control of hepatic cholesterol metabolism by leptin, rats were administered IV (intravenous) leptin, ICV (intracerebroventricular) leptin or saline. A single low dose of ICV leptin was as effective as a continuous IV infusion of high-dose leptin at decreasing the activities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7alpha-hydroxylase. These results indicate th...

Interindividual variability in low density lipoprotein (LDL) cholesterol (LDL-C) response during treatment with statins is well documented but poorly understood. To investigate potential metabolic and genetic determinants of statin responsiveness, 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo, atorvastatin (10 mg/d), bile acid sequ...

Understanding the origin and evolution of cellular processes is fundamental to understand how biological activity has shaped the history of our planet. Among these, aerobic respiration is probably one of the most debated. We have applied a phylogenomics approach to investigate the origin and evolution of dioxygen reductases (O(2)Red), the key enzymes of aerobic respiratory chains. The distribut...

As part of a program aiming at the selection of yeast strains which might be of interest as sources of natural flavours and fragrances, the bioreduction of (4R)-(-)-carvone and (1R)-(-)-myrtenal by whole-cells of non-conventional yeasts (NCYs) belonging to the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazachstania, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma and Wick...

Methods were developed for determination of microsomal HMG-CoA reductase activity from freshly isolated human lymphocytes, monocytes, and granulocytes or cultured human lymphoid cells. Reductase activity in monocytes is approximately twice that in lymphocytes or granulocytes. The activity in cultured cells is approximately 34-fold greater than that in freshly isolated cells. Assay conditions we...

Because the small bowel is a site of significant cholesterol synthesis, we determined the ileal distribution of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of the cholesterol biosynthetic pathway. Immunofluorescence microscopy on unfixed snap-frozen sections of ileum and jejunum from untreated rats or dogs showed HMG-CoA reductase in the absorpt...

Objective(s):Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in ...