Hmg Coa Reductase Inhibitor Mechanism Of Action
By inhibiting this enzyme hmg coa reductase inhibitors decrease cholesterol levels. It s worth noting that statins reduce cholesterol production in the liver.
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Low density lipoprotein ldl carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via the mechanisms.
Hmg coa reductase inhibitor mechanism of action. Nadph dependent ec 1 1 1 34 of the mevalonate pathway the metabolic pathway that produces cholesterol and other isoprenoids normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and. There may also be some reduction in ldl production as a result of inhibition of hepatic synthesis of very low density lipoprotein vldl the. The primary site of action of hmg coa reductase inhibitors is the liver.
Hmgr is the target of statins that are prescribed to improve the quality of life of millions of people worldwide and more recently has been identified as a target for the development of antimicrobial agents. Hmg coa reductase inhibitors competitively inhibit the activity of hmg coa reductase the rate limiting enzyme in cholesterol synthesis. By competitively inhibiting the rate limiting enzyme statins reduce ldl levels in the blood.
Hmg coa reductase is an enzyme. Mevalonate is part of an enzyme cascade that leads to cholesterol synthesis. Hmg coa reductase 3 hydroxy 3 methyl glutaryl coenzyme a reductase officially abbreviated hmgcr is the rate controlling enzyme nadh dependent ec 1 1 1 88.
Recall from a previous discussion that the enzyme hmg coa reductase is an essential enzyme in the cholesterol synthesis pathway. Drugs in this class are hmg coa reductase inhibitors. Statins also known as hmg coa reductase inhibitors are a class of lipid lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease they are the most common cholesterol lowering drugs.
The new inhibitors of hydroxymethylglutaryl coenzyme a hmg coa reductase are synthetic compounds of fungal origin inhibiting a key and unidirectional enzyme in the sterol biosynthetic pathway. 63 inhibition of cholesterol synthesis in the liver leads to upregulation of ldl receptors and an increase in catabolism of ldl cholesterol. Inhibition of this enzyme results in a transient modest decrease in cellular cholesterol concentration.
The seven decades of research on the mechanism of hmg coa reductase hmgr provided a detailed reaction pathway for what is one of the most biomedically important and mechanistically most complex enzymes. Inhibition of hmg coa reductase prevents conversion of hmg coa to mevalonate the rate limiting step in cholesterol biosynthesis. The rate limiting enzyme in the mevalonate pathway.
Mechanism of action and effects pubmed the beneficial effects of statins are the result of their capacity to reduce cholesterol biosyntesis mainly in the liver where they are selectively distributed as well as to the modulation of lipid metabolism derived from their effect of inhibition upon hmg coa reductase. Treatment with hmg coa reductase inhibitors or statins has been shown to reduce plasma ldl cholesterol apolipoprotein apo b and triglyceride concentrations in a variety of hypercholesterolemic subjects 3 4 5 6 7 8 9 10 while modestly increasing levels of high density lipoprotein hdl cholesterol 3.
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