HMGCL

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]

Full Name

3-Hydroxymethyl-3-Methylglutaryl-CoA Lyase

Function

Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. 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.

Biological Process

Ketone body biosynthetic process Source: UniProtKB
Leucine catabolic process Source: GO_Central
Lipid metabolic process Source: BHF-UCL
Mitochondrion organization Source: Ensembl

Cellular Location

Mitochondrion matrix; Peroxisome. Unprocessed form is peroxisomal.

Involvement in disease

3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD):
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.