title: HMG-CoA
text: # HMG-CoA
  
  β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, 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.
  
  HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine. Its immediate precursors are β-methylglutaconyl-CoA (MG-CoA) and β-hydroxy β-methylbutyryl-CoA (HMB-CoA).
  
  HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol.
  
  ## Biosynthesis
  
  * Leucine metabolism in humans
  * L-Leucine
  * Branched-chain amino acid aminotransferase
  * α-Ketoglutarate
  * Glutamate
  * Glutamate
  * Alanine
  * Pyruvate
  * Muscle: α-Ketoisocaproate (α-KIC)
  * Liver: α-Ketoisocaproate (α-KIC)
  * Branched-chain α-ketoacid dehydrogenase (mitochondria)
  * KIC-dioxygenase (cytosol)
  * Isovaleryl-CoA
  * β-Hydroxy β-methylbutyrate (HMB)
  * Excreted in urine (10–40%)
  * HMB-CoA
  * β-Hydroxy β-methylglutaryl-CoA (HMG-CoA)
  * β-Methylcrotonyl-CoA (MC-CoA)
  * β-Methylglutaconyl-CoA (MG-CoA)
  * $CO_2$
  * $CO_2$
  * $O_2$
  * $CO_2$
  * $H_2O$
  * $CO_2$
  * $H_2O$
  * (liver) HMG-CoA lyase
  * Enoyl-CoA hydratase
  * Isovaleryl-CoA dehydrogenase
  * MC-CoA carboxylase
  * MG-CoA hydratase
  * HMG-CoA reductase
  * HMG-CoA  synthase
  * β-Hydroxybutyrate dehydrogenase
  * Mevalonate pathway
  * Thiolase
  * Unknown enzyme
  * β-Hydroxybutyrate
  * Acetoacetyl-CoA
  * Acetyl-CoA
  * Acetoacetate
  * Mevalonate
  * Cholesterol
  * Human metabolic pathway for HMB and isovaleryl-CoA relative to L-leucine. Of the two major pathways, L-leucine is mostly metabolized into isovaleryl-CoA, while only about 5% is metabolized into HMB.
  
  ## 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.
  
  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.
  
  ## Ketogenesis pathway
  
  HMG-CoA lyase breaks it into acetyl CoA and acetoacetate.
  
  