A method for solubilizing HMG-CoA reductase is described that reproducibly yielded approximately 190% of the activity assayed in rat liver microsomes. Optimal solubilization occurred when microsomal membranes were frozen at a fixed concentration, thawed, homogenized in a buffer containing 50% glycerol, and incubated at 37 degrees C for 60 minutes. A rapid spectrophotometric assay of the reducta...

Lipid lowering 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors--statins--significantly diminish the risk of cardiovascular morbidity and mortality in patients with cardiovascular diseases. Moreover, some clinical trials results indicate that this group of drugs reduces blood pressure, especially in patients with hypertension. In the article pleiotropic effects of statins th...

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-R) is the major rate-limiting enzyme of the mevalonate pathway in many organisms, including yeasts. In the yeast Saccharomyces cerevisiae, there are two isoenzymes of HMG-R (Hmg1p and Hmg2p). Both consist of an anchoring transmembrane domain and a catalytic domain. We have removed the known controlling features of HMG-R b...

The RapidFire High-throughput Mass Spectrometry System provides drug discovery researchers with mass spectrometry-based, high-throughput screening solutions for targets that have proven challenging to screen using conventional approaches. These intractable targets have substrates and products that are either too small to label or undergo modifi cations that are diffi cult to detect. RapidFire t...

The current model for reverse cholesterol transport proposes that HDL transports excess cholesterol derived primarily from peripheral cells to the liver for removal. However, recent studies in ABCA1 transgenic mice suggest that the liver itself may be a major source of HDL cholesterol (HDL-C). To directly investigate the hepatic contribution to plasma HDL-C levels, we generated an adenovirus (r...

The structure and biochemical function of the hot dog-fold thioesterase PaaI operative in the aerobic phenylacetate degradation pathway are examined. PaaI showed modest activity with phenylacetyl-coenzyme A, suggestive of a role in coenzyme A release from this pathway intermediate in the event of limiting downstream pathway enzymes. Minimal activity was observed with aliphatic acyl-coenzyme A t...

The preparation of a fluorogenic sensory material for the detection of biomolecules is described. Strategic functionalisation and copolymerisation of a water insoluble organic sensory molecule with hydrophilic comonomers yielded a crosslinked, water-swellable, easy-to-manipulate solid system for water "dip-in" fluorogenic coenzyme A, cysteine, and glutathione detection by means of host-guest in...

Hypercholesterolemia is a well-established risk factor for the development of coronary artery disease (CAD) and for CAD mortality (1). Elevated serum cholesterol levels were also a risk factor for the development of heart failure (HF) in the Framingham study (2). Reduction in serum total cholesterol levels with 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) in p...

1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients. 2. HMGCoAR levels varied four fold (9-40 pmol min-1 mg-1) and biliary cholesterol secre...

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