BioPAX pathway converted from "arginine + H2O => ornithine + urea [ARG1]" in the Reactome database. 3.5.3.1 精氨酸+水= > ornithine + urea [ARG1] 精氨酸+水= > ornithine + urea [ARG1] Cytosolic Arginase 1 (ARG1) trimer catalyzes the hydrolysis of arginine to yield ornithine and urea (DiCostanzo et al. 2005). Patients expressing mutated forms of the enzyme with diminished in vitro arginase activity can accumulate arginine to pathogenic levels in the blood (e.g., Uchino et al. 1995). Authored: D'Eustachio, P, 2003-06-24 00:00:00 Edited: D'Eustachio, P, 2003-06-24 00:00:00 Reactome DB_ID: 29356 1 cytosol GO 0005829 water [ChEBI:15377] water Reactome //www.joaskin.com ChEBI 15377 Reactome DB_ID: 29468 1 L-argininium(1+) [ChEBI:32682] L-argininium(1+) ODKSFYDXXFIFQN-BYPYZUCNSA-O InChI=1S/C6H14N4O2/c7-4(5(11)12)2-1-3-10-6(8)9/h4H,1-3,7H2,(H,11,12)(H4,8,9,10)/p+1/t4-/m0/s1 L-arginine monocation L-argininium C6H15N4O2 (2S)-2-ammonio-5-guanidiniopentanoate 175.20906 L-arginine NC(=[NH2+])NCCC[C@H]([NH3+])C([O-])=O ChEBI 32682 Reactome DB_ID: 29514 1 尿素(ChEBI: 16199) urea ChEBI 16199 Reactome DB_ID: 29498 1 L-ornithine [ChEBI:15729] L-ornithine ChEBI 15729 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 70567 ARG1 trimer [cytosol] ARG1 trimer arginase 1 homotrimer Reactome DB_ID: 70561 3 UniProt:P05089 ARG1 ARG1 ARG1 FUNCTION Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys.FUNCTION Functions in L-arginine homeostasis in nonhepatic tissues characterized by the competition between nitric oxide synthase (NOS) and arginase for the available intracellular substrate arginine. Arginine metabolism is a critical regulator of innate and adaptive immune responses. Involved in an antimicrobial effector pathway in polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated from the phagolysosome and depletes arginine in the microenvironment leading to suppressed T cell and natural killer (NK) cell proliferation and cytokine secretion (PubMed:15546957, PubMed:16709924, PubMed:19380772). In group 2 innate lymphoid cells (ILC2s) promotes acute type 2 inflammation in the lung and is involved in optimal ILC2 proliferation but not survival (By similarity). In humans, the immunological role in the monocytic/macrophage/dendritic cell (DC) lineage is unsure.PATHWAY Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1.SUBUNIT Homotrimer (PubMed:16141327, PubMed:17469833, PubMed:17562323, PubMed:18802628, PubMed:2241902). Interacts with CMTM6 (PubMed:28813417).TISSUE SPECIFICITY Within the immune system initially reported to be selectively expressed in granulocytes (polymorphonuclear leukocytes [PMNs]) (PubMed:15546957). Also detected in macrophages mycobacterial granulomas (PubMed:23749634). Expressed in group2 innate lymphoid cells (ILC2s) during lung disease (PubMed:27043409).INDUCTION By arginine or homoarginine.SIMILARITY Belongs to the arginase family. Homo sapiens NCBI Taxonomy 9606 UniProt P05089 Chain Coordinates 1 EQUAL 322 EQUAL Reactome DB_ID: 29418 6 manganese(2+) [ChEBI:29035] manganese(2+) manganese(II) manganous ion MANGANESE (II) ION manganese, ion (Mn2+) Mn(2+) ChEBI 29035 Reactome Database ID Release 77 70567 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70567 Reactome R-HSA-70567 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70567.1 GO 0004053 GO molecular function Reactome Database ID Release 77 70568 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70568 Reactome Database ID Release 77 70569 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70569 Reactome R-HSA-70569 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70569.3 16141327 Pubmed 2005 Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response Di Costanzo, L Sabio, G Mora, A Rodriguez, PC Ochoa, AC Centeno, F Christianson, DW Proc Natl Acad Sci U S A 102:13058-63 7649538 Pubmed 1995 Molecular basis of phenotypic variation in patients with argininemia Uchino, T Snyderman, SE Lambert, M Qureshi, IA Shapira, SK Sansaricq, C Smit, LM Jakobs, Cornelis Matsuda, I Hum Genet 96:255-60