What is the role of HMG-CoA reductase?
HMG-CoA reductase (HMGR), a highly conserved, membrane-bound enzyme, catalyzes a rate-limiting step in sterol and isoprenoid biosynthesis and is the primary target of hypocholesterolemic drug therapy.
What does HMG-CoA reductase reduce?
Recently, a new class of lipid-lowering drugs, HMG CoA reductase inhibitors, have been introduced. These drugs act by decreasing liver cholesterol synthesis resulting in up-regulation of LDL receptors, increased clearance of LDL from plasma, and diminution of plasma LDL levels.
What is an example of a HMG CoA reductase inhibitor?
Rosuvastatin is the most potent statin followed by atorvastatin. Statins also classify as lipophilic or hydrophilic. Lipophilic statins include simvastatin, lovastatin, and atorvastatin. Hydrophilic statins include pravastatin, fluvastatin, and rosuvastatin.
How does HMG-CoA reductase 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 does HMG-CoA stand for?
β-Hydroxy β-methylglutaryl-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. HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine.
What is the fate of HMG-CoA?
Fates of 3-Hydroxy-3-Methylglutaryl CoA. In the cytosol, HMG-CoA is converted into mevalonate. In mitochondria, it is converted into acetyl CoA and acetoacetate. The synthesis of mevalonate is the committed step in cholesterol formation.
What are HMG-CoA drugs?
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 full form?
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl-CoA, is an intermediate in the mevalonate and ketogenesis pathways. HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine.
Where is HMG-CoA reductase found?
In humans, the gene for HMG-CoA reductase (NADPH) is located on the long arm of the fifth chromosome (5q13. 3-14). Related enzymes having the same function are also present in other animals, plants and bacteria.
What CoA means?
Certificate Of Authenticity
(Certificate Of Authenticity) A document that accompanies software which states that it is an original package from the manufacturer.
What is HMG-CoA pathway?
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.
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.
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.
