Hydroxymethylglutaryl-CoA synthase

Hydroxymethylglutaryl-coenzyme A synthase N terminal
staphylococcus aureus 3-hydroxy-3-methylglutaryl-coa synthase
Identifiers
Symbol	HMG_CoA_synt_N
Pfam	PF01154
Pfam clan	CL0046
InterPro	IPR013528
PROSITE	PDOC00942
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Hydroxymethylglutaryl-coenzyme A synthase C terminal
staphylococcus aureus 3-hydroxy-3-methylglutaryl-coa synthase
Identifiers
Symbol	HMG_CoA_synt_C
Pfam	PF08540
Pfam clan	CL0046
InterPro	IPR013746
PROSITE	PDOC00942
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.

acetyl-CoA + H₂O + acetoacetyl-CoA ${\displaystyle \rightleftharpoons }$ (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.