Hydroxymethylglutaryl-CoA lyase

Hydroxymethylglutaryl-CoA lyase
	Model structure of the human HMG-CoA lyase according to PDB 2cw6 . A monomer is shown; the magnesium (II) ion it contains is shown in blue.
	Existing structural data : 2cw6 , 3MP3 , 3MP4 , 3MP5
Properties of human protein
Mass / length primary structure	298 amino acids
Secondary to quaternary structure	Homodimer
Identifier
Gene name	HMGCL
External IDs	OMIM : 246450 ; UniProt : P35914 ; MGI : 96158 ;
Enzyme classification
EC, category	4.1.3.4 , lyase
Response type	Cleavage of a CC bond
Substrate	HMG-CoA
Products	Acetyl-CoA + acetoacetate
Occurrence
Homology family	HMGCL-like
Parent taxon	Creature
	Orthologue

Hydroxymethylglutaryl-CoA lyase (short: HMG-CoA lyase or HL ) is the enzyme , the cleavage of HMG-CoA into acetyl-CoA and acetoacetate catalyzed . In plants and bacteria, HMG-CoA becomes part of the mevalonate pathway to build up the isoprenoids via an HMG-CoA lyase . In the mitochondria and peroxisomes of vertebrates , HMG-CoA is part of the synthesis of the keto bodies and the breakdown of the amino acid leucine. In humans, the enzyme is localized in fibroblasts , lymphocytes and the liver . Mutations in HMGCL - gene can hereditary enzyme deficiency HMG-CoA lyase deficiency lead of with severe hypoglycemia and coma associated. HL deficiency is extremely rare outside of Saudi Arabia, Portugal, and Japan.

Catalyzed reaction

⇒ +

HMG-CoA is converted to acetyl-CoA and acetoacetate.

The magnesium ion (in green) is complexed by four amino acids and probably two water molecules (in blue). The amino acids are aspartate 42, histidine 233 and 235, and asparagine 275.

Individual evidence

↑ UniProt P35914
↑ Muroi J, Yorifuji T, Uematsu A, et al : Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency . In: Hum. Genet. . 107, No. 4, October 2000, pp. 320-6. PMID 11129331 .
↑ Mitchell GA, Ozand PT, Robert MF, et al : HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q . In: Am. J. Hum. Genet. . 62, No. 2, February 1998, pp. 295-300. doi : 10.1086 / 301730 . PMID 9463337 . PMC 1376904 (free full text).
↑ Ashmarina LI, Rusnak N, Miziorko HM, Mitchell GA: 3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human liver peroxisomes . In: J. Biol. Chem. . 269, No. 50, December 1994, pp. 31929-32. PMID 7527399 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Ketone Body Biosynthesis - Learning and Teaching Materials

Wikibooks: Biochemistry and Pathobiochemistry: beta-Hydroxy-beta-methylglutaryl-CoA - learning and teaching materials

Gopinathrao / reactome.org: HMG CoA ⇒ acetoacetic acid + acetyl CoA

[1] UniProt P35914

[2] Muroi J, Yorifuji T, Uematsu A, et al : Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency . In: Hum. Genet. . 107, No. 4, October 2000, pp. 320-6. PMID 11129331 .

[3] Mitchell GA, Ozand PT, Robert MF, et al : HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q . In: Am. J. Hum. Genet. . 62, No. 2, February 1998, pp. 295-300. doi : 10.1086 / 301730 . PMID 9463337 . PMC 1376904 (free full text).

[4] Ashmarina LI, Rusnak N, Miziorko HM, Mitchell GA: 3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human liver peroxisomes . In: J. Biol. Chem. . 269, No. 50, December 1994, pp. 31929-32. PMID 7527399 .