What is the mechanism of action of HMG-CoA?

What is the mechanism of action of HMG-CoA?

Mechanism of Action: An antihyperlipidemic that inhibits hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the enzyme that catalyzes the early step in cholesterol synthesis. Therapeutic Effect: Decreases LDL and VLDL cholesterol, and plasma triglyceride levels; increases HDL cholesterol concentration.

What is the mechanism of action of HMG CoA reductase inhibitors?

Introduction. Also known as statins, HMG-CoA reductase inhibitors work by inhibiting the synthesis of cholesterol in the liver by the enzyme HMG-CoA reductase.

What is the function of HMG-CoA reductase?

HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis. The expression level of this membrane-bound enzyme is controlled by many factors that in turn regulate cholesterol synthesis and cellular cholesterol homeostasis (reviewed in [1]).

What are reversible inhibitors of HMG-CoA reductase?

Compactin is a reversible inhibitor of HMG CoA reductase (EC 1.1. 1.34). Originally isolated from Penicillium citrinum, compactin was found to inhibit cholesterol synthesis Endo and Kuroda (1976). It was the first HMG CoA reductase inhibitor employed for lowering cholesterol levels in humans.

Which is HMG CoA reductase inhibitor?

A substance that blocks an enzyme needed by the body to make cholesterol and lowers the amount of cholesterol in the blood. HMG-CoA reductase inhibitor drugs are called statins. Also called hydroxymethylglutaryl-coenzyme A reductase inhibitor.

What is HMG-CoA reductase pathway?

HMG-CoA Reductase (or 3-hydroxy-3-methyl-glutaryl-CoA reductase or HMGR) is the rate-controlling enzyme of the mevalonate pathway, responsible for cholesterol and other isoprenoid biosynthesis. HMGR is a transmembrane protein, containing 8 domains, that is anchored in the membrane of the endoplasmic reticulum.

What does HMG-CoA reductase stand for?

HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, EC 1.1. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia.

What is the mechanism of action for statins?

Mechanism of Action Statins work by competitively blocking the active site of the first and key rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase. Inhibition of this site prevents substrate access, thereby blocking the conversion of HMG-CoA to mevalonic acid.

How does insulin regulate HMG-CoA reductase?

Insulin stimulates HMG-CoA reductase activity likely by increasing the rate of transcription, whereas glucagon acts by opposing this effect. Deficiencies in those hormones that act to increase hepatic HMG-CoA reductase gene expression lead to elevations in serum cholesterol levels.

What happens if HMG-CoA reductase activity is inhibited?

Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia.

Why does insulin activate HMG-CoA reductase?

These include insulin, glucagon, glucocorticoids, thyroid hormone and estrogen. Insulin stimulates HMG-CoA reductase activity likely by increasing the rate of transcription, whereas glucagon acts by opposing this effect. Estrogen acts to increase hepatic HMG-CoA reductase activity primarily by stabilizing the mRNA.

What is HMG-CoA reductase quizlet?

-b/c HMG CoA Reductase is the rate-limiting step of cholesterol synthesis. -decreases cholesterol levels.

Which is the regulatory point of HMG-CoA reductase?

In the final step of mevalonate biosynthesis, HMG-CoA reductase, an NADPH -dependent oxidoreductase, catalyzes the conversion of HMG-CoA into mevalonate, which is the primary regulatory point in this pathway.

Are there any statins that inhibit HMG-CoA reductase?

Statins, which inhibit HMG-CoA reductase, the rate limiting step in cholesterol synthesis, are thought to exert much of their LDL-C lowering effect by increasing hepatic availability of LDL receptors. The first statin, lovastatin, was approved by the FDA in 1987.

How is HMG-CoA reductase degradation accelerated by sterol?

HMG-CoA reductase degradation is accelerated when cells accumulate the sterol intermediate 24,25-dihydrolanosterol ( Fig. 1), and protein turnover is further stimulated by the non-sterol isoprenoid geranylgeranyl pyrophosphate (Schumacher et al., 2015).

What happens when HMG-CoA is converted to mevalonic acid?

The HMG-CoA reductase (HMGCR), converts HMG-CoA into mevalonic acid. Thus, when HMGCR activities are reduced, the cell associated cholesterols are also reduced. This results in the activation of SREBP-2-mediated signaling pathways.