In biochemistry, hydroxymethylglutaryl-CoA synthase or HMG-CoA synthase EC 2.3.3.10 is an enzyme which catalyzes the reaction in which acetyl-CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This reaction comprises the second step in the mevalonate-dependent isoprenoid biosynthesis pathway. 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. This results in shunting of excess acetyl-CoA into the ketone synthesis pathway via HMG-CoA, leading to the development of diabetic ketoacidosis.
HMG-CoA synthase reaction
Quick Facts 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble), Identifiers ...
Close
Quick Facts 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial), Identifiers ...
Close
Quick Facts Identifiers, Symbol ...
Close
Quick Facts Identifiers, Symbol ...
Close
acetyl-CoA + H
2O + acetoacetyl-CoA
![{\displaystyle \rightleftharpoons }](//wikimedia.org/api/rest_v1/media/math/render/svg/1c37b981df851b9e54e489e017b1481e37d418f3)
(
S)-3-hydroxy-3-methylglutaryl-CoA + CoA
The 3 substrates of this enzyme are acetyl-CoA, H2O, and acetoacetyl-CoA, whereas its two products are (S)-3-hydroxy-3-methylglutaryl-CoA and CoA.
In humans, the protein is encoded by the HMGCS1 gene on chromosome 5.