How do HMG-CoA reductase inhibitors work?
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, more popularly known as statins, work by reducing the cholesterol levels in the body. HMG-CoA inhibitors interfere with the ability of the body to build cholesterol from dietary fat.
What pathway is HMG-CoA reductase?
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 happens when you inhibit HMG-CoA reductase?
Inhibition of HMG-CoA reductase, a rate-limiting enzyme in hepatic cholesterol synthesis by statins, results in the reduction of intracellular cholesterol content that in turn induces an increase in SREBP-2-mediated hepatic LDL receptor synthesis (Sahebkar and Watts, 2013b) (Chapter 11).
What is HMG-CoA reductase a target for?
Thus, HMG-CoA reductase is a unique molecular target for anti-cancer therapy; it holds a pivotal role in the well-defined MVA pathway, and a specific family of inhibitors is available for immediate application in the cancer clinic. The mevalonate pathway.
What do HMG-CoA inhibitors do?
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.
What is the chemical name of HMG-CoA?
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl-CoA, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase.
Which amino acid is involved in binding of HMG-CoA reductase?
HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, EC 1.1.
What does HMG-CoA stand for?
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl-CoA, is an intermediate in the mevalonate and ketogenesis pathways.
Is HMG-CoA reductase in the liver?
HMG-CoA reductase (HMGR) catalyzes the rate-controlling step in cholesterol production. This enzyme is highly expressed in the liver, where it is subject to extensive hormonal and dietary regulation.
How are HMG-CoA reductase inhibitors used in heart disease?
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors specifically inhibit HMG-CoA reductase in the liver, thereby inhibiting the biosynthesis of cholesterol. These drugs significantly reduce plasma cholesterol level and long term treatment reduces morbidity and mortality associated with coronary heart disease.
Where does HMG-CoA reductase accumulate in the body?
Thus, active HMG-CoA reductase enzyme accumulates in the endoplasmic reticulum in response to (1) a slow rate of degradation of the protein and (2) increased transcription and enzyme synthesis (Figure 2 ). Since HMG-CoA reductase is the rate-limiting enzyme, the net result is increased cholesterol synthesis.
Which is the isoenzyme involved in the metabolic transformation of HMG-CoA?
Cytochrome P450 (CYP) 3A4 is the main isoenzyme involved in the metabolic transformation of HMG-CoA reductase inhibitors. Individuals with both low hepatic and low gastrointestinal tract levels of CYP3A4 expression may be at in increased risk of myotoxicity due to potentially higher HMG-CoA reductase inhibitor plasma concentrations.
Which is enzyme inactivates HMG-CoA carboxylase?
An excellent review on regulation of the mevalonate pathway by Nobel Laureates Joseph Goldstein and Michael Brown adds specifics: HMG-CoA reductase is phosphorylated and inactivated by an AMP-activated protein kinase, which also phosphorylates and inactivates acetyl-CoA carboxylase, the rate-limiting enzyme…