Hydroxymethylglutaryl-CoA synthase, mitochondrial
Function
Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate.
Involvement in disease
3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency
HMGCS2D
A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
Post-translational modifications
Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-83 and Lys-310, inhibits the enzymatic activity.
Sequence Similarities
Belongs to the thiolase-like superfamily. HMG-CoA synthase family.
Tissue Specificity
Expression in liver is 200-fold higher than in any other tissue. Low expression in colon, kidney, testis, and pancreas. Very low expression in heart and skeletal muscle (PubMed:16940161, PubMed:21952825, PubMed:7893153). Not detected in brain (PubMed:21952825).
Isoform 3
Highest expression detected in heart and skeletal muscle.
Cellular localization
- Mitochondrion
Alternative names
HMG-CoA synthase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, HMGCS2