Names & Taxonomy

Uniprot ID:
P35914
Entry Name:
HMGCL_HUMAN
Status:
reviewed
Protein Names:
Hydroxymethylglutaryl-CoA lyase, mitochondrial (HL) (HMG-CoA lyase) (EC 4.1.3.4) (3-hydroxy-3-methylglutarate-CoA lyase)
Gene Names:
HMGCL
Gene Names Primary:
HMGCL
Organism:
Homo sapiens (Human)

Structure

Length:
325
Sequence:
MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Mitochondrion matrix. Peroxisome. Note=Unprocessed form is peroxisomal.

Function

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.
Pathway:
Metabolic intermediate metabolism; (S)-3-hydroxy-3-methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA: step 1/1.
Catalytic Activity:
(S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate.
Cofactor:
COFACTOR: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=200 uM for magnesium ion
Enzyme Regulation:
ENZYME REGULATION: Stimulated by reducing agents such as dithiothreitol (DTT).
Active Site:
ACT_SITE 266 266
Gene Ontology Go:
mitochondrial inner membrane
mitochondrial matrix
mitochondrion
peroxisome
carboxylic acid binding
fatty-acyl-CoA binding
hydroxymethylglutaryl-CoA lyase activity
magnesium ion binding
manganese ion binding
metal ion binding
protein homodimerization activity
receptor binding
acyl-CoA metabolic process
cellular ketone body metabolic process
cellular lipid metabolic process
ketone body biosynthetic process
leucine catabolic process
liver development
mitochondrion organization
protein tetramerization
response to fatty acid
response to nutrient
response to starvation
small molecule metabolic process
Gene Ontology Biological Process:
acyl-CoA metabolic process
cellular ketone body metabolic process
cellular lipid metabolic process
ketone body biosynthetic process
leucine catabolic process
liver development
mitochondrion organization
protein tetramerization
response to fatty acid
response to nutrient
response to starvation
small molecule metabolic process
Gene Ontology Molecular Function:
carboxylic acid binding
fatty-acyl-CoA binding
hydroxymethylglutaryl-CoA lyase activity
magnesium ion binding
manganese ion binding
metal ion binding
protein homodimerization activity
receptor binding
Gene Ontology Cellular Component:
mitochondrial inner membrane
mitochondrial matrix
mitochondrion
peroxisome
Keywords:
3D-structure
Acetylation
Alternative splicing
Complete proteome
Disease mutation
Disulfide bond
Lyase
Metal-binding
Mitochondrion
Peroxisome
Reference proteome
Transit peptide

Publication

PubMed ID:
8440722 14702039 16710414 15489334 8617516 21952825 7527399 8566388 12464283 12874287 15122894 19608861 21269460 22865860 22847177 24275569 25944712 16330550 8798725 9463337 9784232 11129331 12746442 17173698 16601870 17459752 19036343 19177531