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HMG coenzyme A.svg
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
3D model (JSmol)
Molar mass 911.661 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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. The research of Minor J. Coon and Bimal Kumar Bachhawat in the 1950s at University of Illinois led to its discovery.[1][2]

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]


Mevalonate pathway

Mevalonate synthesis begins with the beta-ketothiolase-catalyzed Claisen condensation of two molecules of acetyl-CoA to produce acetoacetyl CoA. The following reaction involves the joining of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA, a process catalyzed by HMG-CoA synthase.[7]

In the final step of mevalonate biosynthesis, HMG-CoA reductase, an NADPH-dependent oxidoreductase, catalyzes the conversion of HMG-CoA into mevalonate, which is the primary regulatory point in this pathway. Mevalonate serves as the precursor to isoprenoid groups that are incorporated into a wide variety of end-products, including cholesterol in humans.[8]

Mevalonate pathway

Ketogenesis pathway

HMG-CoA lyase breaks it into acetyl CoA and acetoacetate.

See also


  1. Sarkar, Debi P. (2015). "Classics in Indian Medicine". The National Medical Journal of India (28): 3. 
  2. Surolia, Avadhesha (1997). "An outstanding scientist and a splendid human being". Glycobiology 7 (4): v–ix. doi:10.1093/glycob/7.4.453. 
  3. "Valine, leucine and isoleucine degradation - Reference pathway". Kanehisa Laboratories. 27 January 2016. 
  4. 4.0 4.1 4.2 "International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)". Journal of the International Society of Sports Nutrition 10 (1): 6. February 2013. doi:10.1186/1550-2783-10-6. PMID 23374455. 
  5. 6.0 6.1 6.2 Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.). Academic Press. May 2015. pp. 385–388. ISBN 978-0-12-387784-0. Retrieved 6 June 2016. "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" 
    Figure 8.57: Metabolism of L-leucine
  6. Garrett, Reginald H. (2013). Biochemistry. Cengage Learning. pp. 856. ISBN 978-1-305-57720-6. 
  7. "Molecular modeling of the reaction pathway and hydride transfer reactions of HMG-CoA reductase". Biochemistry 51 (40): 7983–95. October 2012. doi:10.1021/bi3008593. PMID 22971202.