HMGCL

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.

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.

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

Belongs to the HMG-CoA lyase family.

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%).

• Mitochondrion matrix
• Peroxisome
• Unprocessed form is peroxisomal.

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

• entrezGene:3155
• omim:613898
• omim:246450
• swissprot:P35914

Proteins

Metabolism

34360Da