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HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine. [3] Its immediate precursors are β-methylglutaconyl-CoA (MG-CoA) and β-hydroxy β-methylbutyryl-CoA (HMB-CoA). [4][5][6] HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary ...
HMG-CoA is an intermediate in both cholesterol synthesis and ketogenesis. This reaction is overactivated in patients with diabetes mellitus type 1 if left untreated, due to prolonged insulin deficiency and the exhaustion of substrates for gluconeogenesis and the TCA cycle , notably oxaloacetate .
HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, EC 1.1.1.88; NADPH-dependent, EC 1.1.1.34) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a ...
HMG-CoA synthase: Acetoacetyl-CoA condenses with another Acetyl-CoA molecule to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA reductase: HMG-CoA is reduced to mevalonate by NADPH. This is the rate limiting step in cholesterol synthesis, which is why this enzyme is a good target for pharmaceuticals . mevalonate-5-kinase
Besides its role in the synthesis of ketone bodies, HMG-CoA is also an intermediate in the synthesis of cholesterol, but the steps are compartmentalised. [1] [2] Ketogenesis occurs in the mitochondria, whereas cholesterol synthesis occurs in the cytosol, hence both processes are independently regulated. [2]
Statins (or HMG-CoA reductase inhibitors) are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease. [1]Low-density lipoprotein (LDL) carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via the mechanisms described by the lipid hypothesis.
Domains. InterPro. 3-Hydroxy-3-methylglutaryl-CoA lyase (or HMG-CoA lyase) is an enzyme (EC 4.1.3.4 that in human is encoded by the HMGCL gene located on chromosome 1. It is a key enzyme in ketogenesis (ketone body formation). It is a ketogenic enzyme in the liver that catalyzes the formation of acetoacetate from HMG-CoA within the mitochondria.
The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular ...