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HMGCL

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.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

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

Sequence similarities

Belongs to the HMG-CoA lyase family.

Tissue specificity

Highest expression in liver. Expressed in pancreas, kidney, 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%).

Cellular localization

  • Mitochondrion matrix
  • Peroxisome
  • Unprocessed form is peroxisomal.

Alternative names

  • HL
  • HMG-CoA lyase
  • 3-hydroxy-3-methylglutarate-CoA lyase
  • HMGCL

Target type

Proteins

Molecular weight

34360Da