HMGCS2
HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2) is a mitochondrial enzyme that catalyses the first reaction of ketogenesis, the pathway that supplies lipid-derived energy when carbohydrate is scarce. It is also known as mitochondrial hydroxymethylglutaryl-CoA synthase. Browse Assay Genie's current range of HMGCS2 research reagents below, or read on for the biology behind the target.
HMGCS2 catalyses the first irreversible step in ketogenesis. It condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA. In the pathway described in the UniProt annotation, HMG-CoA is then converted by HMG-CoA reductase (HMGCR) into mevalonate. Ketogenesis is a metabolic pathway that provides lipid-derived energy to various organs during carbohydrate deprivation, such as fasting, so the HMGCS2 enzyme sits at a key control point of fasting metabolism.
The HMGCS2 gene encodes a protein that belongs to the HMG-CoA synthase family and, more broadly, the thiolase-like superfamily. The enzyme is located in the mitochondrion, and its classification under EC 2.3.3.10 reflects its synthase activity. Alternatively spliced transcript variants encoding different isoforms have been reported for this gene. Researchers working on the HMGCS2 protein often consider it alongside HMGCS1, the other member of the HMG-CoA synthase family.
The gene was previously named 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial), and the mouse and rat orthologs are both written Hmgcs2. Mutations in HMGCS2 are associated with HMG-CoA synthase deficiency, which makes the enzyme relevant to studies of inherited disorders of ketone body production and of energy metabolism during fasting.
HMGCS2 catalyses the first reaction of ketogenesis, which supplies lipid-derived energy to organs when carbohydrate is limited, as in fasting.
As a mitochondrial member of the thiolase-like superfamily, HMGCS2 is a subject for studies of acetyl-CoA condensation and HMG-CoA formation.
Mutations in the HMGCS2 gene are associated with HMG-CoA synthase deficiency, making it a focus for research into disorders of ketone body production.
HMGCS2 produces HMG-CoA, which HMG-CoA reductase (HMGCR) converts into mevalonate, connecting ketogenic and mevalonate metabolism.
HMGCS2 is a mitochondrial enzyme that catalyses the first irreversible step in ketogenesis. It condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which HMG-CoA reductase (HMGCR) converts into mevalonate. Ketogenesis provides lipid-derived energy during carbohydrate deprivation such as fasting.
The official name is 3-hydroxy-3-methylglutaryl-CoA synthase 2, and UniProt lists it as hydroxymethylglutaryl-CoA synthase, mitochondrial. Earlier names included the term 'mitochondrial' in brackets. Alternatively spliced transcript variants encoding different isoforms have been found for the HMGCS2 gene.
Mutations in HMGCS2 are associated with HMG-CoA synthase deficiency. Orthologs named Hmgcs2 exist in both mouse and rat, so rodent models can be used to study the gene. Check the datasheet of any product for its validated reactivity.
Other members of the HMG-CoA synthase family and related enzymes of ketogenesis and the mevalonate pathway with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P54868; product specifications from Assay Genie datasheets.