Arginase 1

Arginase-1
	Ribbon model of rat arginase 1 complexed with hydroxyarginine, according to PDB 1HQF
	Existing structural data: s. UniProt
Properties of human protein
Mass / length primary structure	322 amino acids
Secondary to quaternary structure	Homotrimer
Cofactor	2 Mn 2+
Isoforms	3
Identifier
Gene name	ARG1
External IDs	GeneCards : ARG1 ; OMIM : 608313 ; UniProt : P05089 ; MGI : 88070 ; CAS number : 9000-96-8;
Enzyme classification
EC, category	3.5.3.1 , hydrolase
Response type	Hydrolysis of a CN bond
Substrate	Arginine + H 2 O
Products	Ornithine + urea
Occurrence
Homology family	Liver arginase
Parent taxon	Vertebrates
	Orthologue

Arginase 1 (also: Leber-Arginase , ARG1 ) is the enzyme that catalyzes the last reaction step in the urea cycle of vertebrates . The arginases are a group of isozymes that occur in all living things and break down the amino acid arginine into ornithine and urea . When people can mutations in ARG1 - gene this one to Arginase deficiency, and urea cycle disorder with hyperammonemia lead. Variants of arginase were associated with side effects on beta-2 sympathomimetics in asthma patients . Another variant showed a connection with the risk of myocardial infarction .

Neutrophil granulocytes modulate the immune response by secreting arginase. Arginase is overexpressed in psoriatic lesions. This leads to a reduced availability of nitric oxide in the tissue, since arginase competes with NO synthase for arginine . The same competition within macrophages is exploited by intracellular pathogens such as Mycobacterium tuberculosis , Toxoplasma gondii, and others to evade the immune response.

The cAMP -dependent regulation of ARG1 expression is modulated by protein kinase AI and is dependent on histone deacetylation.

Catalyzed reaction

+ H ₂ O ⇔ +

Arginine is hydrolyzed to ornithine and urea.

Individual evidence

↑ UniProt P05089
↑ Litonjua AA, Lasky-Su J, K Schneiter, et al. : ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts . In: Am. J. Respir. Crit. Care Med . 178, No. 7, October 2008, pp. 688-94. doi : 10.1164 / rccm.200709-1363OC . PMID 18617639 .
↑ Dumont J, Zureik M, Cottel D, et al. : Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima media thickness . In: J. Med. Genet. . 44, No. 8, August 2007, pp. 526-31. doi : 10.1136 / jmg.2006.047449 . PMID 17369504 .
↑ Harpster MH, Bandyopadhyay S, Thomas DP, et al. : Earliest changes in the left ventricular transcriptome postmyocardial infarction . In: Mamm. Genomes . 17, No. 7, July 2006, pp. 701-15. doi : 10.1007 / s00335-005-0120-1 . PMID 16845475 .
↑ Jacobsen LC, Theilgaard-Mönch K, Christensen EI, Borregaard N: Arginase 1 is expressed in myelocytes / metamyelocytes and localized in gelatinase granules of human neutrophils . In: Blood . 109, No. 7, April 2007, pp. 3084-7. doi : 10.1182 / blood-2006-06-032599 . PMID 17119118 .
↑ Bruch-Gerharz D, Schnorr O, Suschek C, et al. : Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation . In: Am. J. Pathol. . 162, No. 1, January 2003, pp. 203-11. PMID 12507903 . PMC 1851107 (free full text).
↑ El Kasmi KC, Qualls JE, Pesce JT, et al. : Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens . In: Nat. Immunol. . 9, No. 12, December 2008, pp. 1399-406. doi : 10.1038 / ni.1671 . PMID 18978793 .
↑ Haffner I Teupser D, Holdt LM, Ernst J, Burkhardt R, Thiery J: Regulation of arginase-1 expression in macrophages by a protein kinase A type I and histone deacetylase dependent pathway . In: J. Cell. Biochem. . 103, No. 2, February 2008, pp. 520-7. doi : 10.1002 / jcb.21422 . PMID 17577214 .

Web links

Wikibooks: Urea Cycle - Learning and Teaching Materials

reactome: arginine → ornithine + urea

[1] UniProt P05089

[2] Litonjua AA, Lasky-Su J, K Schneiter, et al. : ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts . In: Am. J. Respir. Crit. Care Med . 178, No. 7, October 2008, pp. 688-94. doi : 10.1164 / rccm.200709-1363OC . PMID 18617639 .

[3] Dumont J, Zureik M, Cottel D, et al. : Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima media thickness . In: J. Med. Genet. . 44, No. 8, August 2007, pp. 526-31. doi : 10.1136 / jmg.2006.047449 . PMID 17369504 .

[4] Harpster MH, Bandyopadhyay S, Thomas DP, et al. : Earliest changes in the left ventricular transcriptome postmyocardial infarction . In: Mamm. Genomes . 17, No. 7, July 2006, pp. 701-15. doi : 10.1007 / s00335-005-0120-1 . PMID 16845475 .

[5] Jacobsen LC, Theilgaard-Mönch K, Christensen EI, Borregaard N: Arginase 1 is expressed in myelocytes / metamyelocytes and localized in gelatinase granules of human neutrophils . In: Blood . 109, No. 7, April 2007, pp. 3084-7. doi : 10.1182 / blood-2006-06-032599 . PMID 17119118 .

[6] Bruch-Gerharz D, Schnorr O, Suschek C, et al. : Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation . In: Am. J. Pathol. . 162, No. 1, January 2003, pp. 203-11. PMID 12507903 . PMC 1851107 (free full text).

[7] El Kasmi KC, Qualls JE, Pesce JT, et al. : Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens . In: Nat. Immunol. . 9, No. 12, December 2008, pp. 1399-406. doi : 10.1038 / ni.1671 . PMID 18978793 .

[8] Haffner I Teupser D, Holdt LM, Ernst J, Burkhardt R, Thiery J: Regulation of arginase-1 expression in macrophages by a protein kinase A type I and histone deacetylase dependent pathway . In: J. Cell. Biochem. . 103, No. 2, February 2008, pp. 520-7. doi : 10.1002 / jcb.21422 . PMID 17577214 .