HMGCS2

The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting. Mutations in this gene are associated with HMG-CoA synthase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

Full Name

3-Hydroxy-3-Methylglutaryl-CoA Synthase 2

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.

Biological Process

Acetyl-CoA metabolic process Source: UniProtKB
Adipose tissue development Source: Ensembl
Brain development Source: Ensembl
Cellular response to amino acid stimulus Source: Ensembl
Cellular response to fatty acid Source: Ensembl
Cellular response to glucocorticoid stimulus Source: Ensembl
Cellular response to insulin stimulus Source: Ensembl
Cellular response to lipopolysaccharide Source: Ensembl
Cholesterol biosynthetic process Source: UniProtKB-KW
Farnesyl diphosphate biosynthetic process, mevalonate pathway Source: GO_Central
Ketone body biosynthetic process Source: UniProtKB
Kidney development Source: Ensembl
Liver development Source: Ensembl
Lung development Source: Ensembl
Midgut development Source: Ensembl
Multicellular organismal response to stress Source: Ensembl
Response to cAMP Source: Ensembl
Response to ethanol Source: Ensembl
Response to glucagon Source: Ensembl
Response to growth hormone Source: Ensembl
Response to linoleic acid Source: Ensembl
Response to metal ion Source: Ensembl
Response to monosaccharide Source: Ensembl
Response to nutrient Source: Ensembl
Response to prostaglandin F Source: Ensembl
Response to starvation Source: Ensembl
Response to temperature stimulus Source: Ensembl
Response to testosterone Source: Ensembl
Response to triglyceride Source: Ensembl
Response to xenobiotic stimulus Source: Ensembl

Cellular Location

Mitochondrion

Involvement in disease

3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D):
A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly.

PTM

Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-83 and Lys-310, inhibits the enzymatic activity.