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| Names | |
|---|---|
| IUPAC name (9R,21S)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9,21-tetrahydroxy-8,8,21-trimethyl-10,14,19-trioxo-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic acid 3,5-dioxide | |
| Other names 3-hydroxy-3-methylglutaryl CoA; 3-hydroxy-3-methylglutaryl coenzyme A | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChemSpider |
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| ECHA InfoCard | 100.014.820 |
| MeSH | HMG-CoA |
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| Properties | |
| C27H44N7O20P3S | |
| Molar mass | 911.661 g/mol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in themevalonate andketogenesis pathways. It is formed fromacetyl CoA andacetoacetyl CoA byHMG-CoA synthase. The research ofMinor J. Coon andBimal Kumar Bachhawat in the 1950s atUniversity of Illinois led to its discovery.[1][2]
HMG-CoA is ametabolic intermediate in themetabolism of thebranched-chain amino acids, which includeleucine,isoleucine, andvaline.[3] Its immediate precursors areβ-methylglutaconyl-CoA (MG-CoA) andβ-hydroxy β-methylbutyryl-CoA (HMB-CoA).[4][5][6]
HMG-CoA reductase catalyzes the conversion of HMG-CoA tomevalonic acid, a necessary step in the biosynthesis of cholesterol.
 Muscle:α-Ketoisocaproate (α-KIC) Liver:α-Ketoisocaproate (α-KIC) Excreted in urine (10–40%) β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) β-Methylcrotonyl-CoA (MC-CoA) β-Methylglutaconyl-CoA (MG-CoA) Unknown enzyme  |
Mevalonate synthesis begins with thebeta-ketothiolase-catalyzedClaisen condensation of two molecules ofacetyl-CoA to produceacetoacetyl CoA. The following reaction involves the joining ofacetyl-CoA andacetoacetyl-CoA to form HMG-CoA, a process catalyzed byHMG-CoA synthase.[8]
In the final step ofmevalonate biosynthesis,HMG-CoA reductase, anNADPH-dependentoxidoreductase, catalyzes the conversion of HMG-CoA intomevalonate, which is the primary regulatory point in this pathway.Mevalonate serves as the precursor toisoprenoid groups that are incorporated into a wide variety of end-products, includingcholesterol in humans.[9]
HMG-CoA lyase breaks it intoacetyl CoA andacetoacetate.
HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).
Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds
HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).
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