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MGP001465

UniProt Annotations

Entry Information
Gene Name3-hydroxymethyl-3-methylglutaryl-CoA lyase
Protein EntryHMGCL_HUMAN
UniProt IDP35914
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P35914-1; Sequence=Displayed; Name=2; Synonyms=HMGCS2delta5,6; IsoId=P35914-2; Sequence=VSP_047444; Note=The transcript is not translated, but would result in a catatically impaired product if it was.; Name=3; Synonyms=HMGCS2delta5,6,7; IsoId=P35914-3; Sequence=VSP_047444, VSP_043788; Note=Very low expression. The transcript is not translated, but would result in a catatically inactive product if it was.;
Biophysicochemical PropertiesKinetic parameters: KM=200 uM for magnesium ion {ECO:0000269|PubMed:12874287, ECO:0000269|PubMed:15122894}; KM=48 uM for HMG-CoA {ECO:0000269|PubMed:12874287, ECO:0000269|PubMed:15122894}; Vmax=191 umol/min/mg enzyme {ECO:0000269|PubMed:12874287, ECO:0000269|PubMed:15122894};
Catalytic Activity(S)-3-hydroxy-3-methylglutaryl-CoA = acetyl- CoA + acetoacetate. {ECO:0000255|PROSITE-ProRule:PRU10115, ECO:0000269|PubMed:22847177, ECO:0000269|PubMed:22865860}.
CofactorName=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000269|PubMed:12874287};
Disease3-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. {ECO:0000269|PubMed:11129331, ECO:0000269|PubMed:12746442, ECO:0000269|PubMed:16601870, ECO:0000269|PubMed:17173698, ECO:0000269|PubMed:17459752, ECO:0000269|PubMed:19036343, ECO:0000269|PubMed:19177531, ECO:0000269|PubMed:8798725, ECO:0000269|PubMed:9463337, ECO:0000269|PubMed:9784232}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationStimulated by reducing agents such as dithiothreitol (DTT). {ECO:0000269|PubMed:12874287}.
FunctionKey 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. {ECO:0000269|PubMed:22847177, ECO:0000269|PubMed:22865860, ECO:0000269|PubMed:8566388}.
PathwayMetabolic intermediate metabolism; (S)-3-hydroxy-3- methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3- methylglutaryl-CoA: step 1/1.
SimilarityBelongs to the HMG-CoA lyase family. {ECO:0000305}.
Subcellular LocationMitochondrion matrix. Peroxisome. Note=Unprocessed form is peroxisomal.
SubunitHomodimer; disulfide-linked. Can also form homotetramers. {ECO:0000269|PubMed:12464283, ECO:0000269|PubMed:16330550}.
Tissue SpecificityHighest 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%). {ECO:0000269|PubMed:21952825}.
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