HMG-CoA
# 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.

