The coordinated control of cholesterol biosynthesis and esterification by 25-hydroxycholesterol was studied in the macrophage-like cell line P388D1. Since 25-hydroxycholesterol rapidly stimulated incorporation of [3H]oleate into the cholesteryl ester fraction of these cells, we have tested the possibility that the well-known inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA...

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme of the mevalonate pathway, the diverse array of end products of which are vital for a variety of cellular functions, including cholesterol synthesis and cell cycle progression. We showed previously that this enzyme holds a critical role in regulating tumor cell fate, including cell death, as its expression is down-re...

Procedures were developed for the determination of the activity of the microsomal enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase, EC 1.1.1.34) in human liver. The enzyme assay could be carried out with as little as 20 mg of fresh liver tissue, thus making the method applicable to specimens obtained by percutaneous liver biopsy. Experiments were carried out to determine optim...

Dermographism, or skin writing, is the most common type of physical urticaria, manifesting as pruritic linear wheals and erythema secondary to minor trauma, such as rubbing or stroking the skin. This reaction in the superficial dermis occurs within seconds to minutes after mechanical irritation and typically resolves within 1 to 2 hours. Usually there are no associated systemic signs and sympto...

1 Background: 3-hydroxy-2-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors are effective lipid-lowering agents that also inhibit the growth of colon cancer cell lines and were noted to be associated with a reduced risk of colorectal cancer (CRC) in a randomized clinical trial of patients with myocardial infarction. We investigated the association between HMG CoA reductase inhibitors and...

Acyl-coenzyme A:cholesterol O-acyltransferase (ACATase; EC 2.3.1.26) is a membrane-bound microsomal enzyme that catalyzes the formation of long-chain fatty-acyl cholesterol esters in rat liver and other tissues. This enzyme is important in regulating the concentration of unesterified cholesterol in the cell. Having recently demonstrated that rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reduc...

Under most experimental conditions, there is a covariation between the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, and the rate-limiting enzyme in bile acid biosynthesis, cholesterol 7a-hydroxylase. The most simple explanation for the coupling between the two enzymes is that newly synthesized cholesterol is a substrate for an unsaturated cholesterol 7a-hydroxylase and t...

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...

The enoyl reductase from Mycobacterium tuberculosis (MtInhA) was shown to be a major target for isoniazid, the most prescribed first-line anti-tuberculosis agent. MtInhA (EC 1.3.1.9) protein catalyzes hydride transfer 4S hydrogen of β-NADH carbon-3 long-chain 2-trans-enoyl thioester substrates (enoyl-ACP or enoyl-CoA) yield NAD+ and acyl-ACP acyl-CoA products. latter are long carbon chains mero...

Sequence comparisons have implied the presence of genes encoding enzymes of the mevalonate pathway for isopentenyl diphosphate biosynthesis in the gram-positive pathogen Staphylococcus aureus. In this study we showed through genetic disruption experiments that mvaA, which encodes a putative class II 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is essential for in vitro growth of S...