HMGCL Antibody – Mouse Monoclonal

The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Function: Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism. Ref.11 Ref.17 Ref.18

Catalytic activity: (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate. Ref.17 Ref.18

Cofactor: Divalent metal cations. Ref.13

Enzyme regulation: Stimulated by reducing agents such as dithiothreitol (DTT). Ref.13

Pathway: Metabolic intermediate metabolism; (S)-3-hydroxy-3-methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA: step 1/1.

Subunit structure: Homodimer; disulfide-linked. Can also form homotetramers. Ref.12 Ref.19

Subcellular location: Mitochondrion matrix. Peroxisome. Note: Unprocessed form is peroxisomal. Ref.10 Ref.12

Tissue specificity: Highest expression in liver. Expressed in pancreas, kidey, intestine, testis, fibroblasts and lymphoblasts. Very low expression in brain and skeletal muscle. The relative expression of isoform 2 (at mRNA level) is highest in heart (30%), skeletal muscle (22%), and brain (14%). Ref.9

Involvement in disease: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:246450]: An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29

Sequence similarities: Belongs to the HMG-CoA lyase family.

Biophysicochemical propertiesKinetic parameters:KM=200 µM for magnesium ion Ref.13 Ref.14KM=48 µM for HMG-CoAVmax=191 µmol/min/mg enzyme