» Articles » PMID: 21494411

Argininosuccinate Synthase: at the Center of Arginine Metabolism

Overview
Specialty Biochemistry
Date 2011 Apr 16
PMID 21494411
Citations 94
Authors
Affiliations
Soon will be listed here.
Abstract

The levels of L-arginine, a cationic, semi-essential amino acid, are often controlled within a cell at the level of local availability through biosynthesis. The importance of this temporal and spatial control of cellular L-arginine is highlighted by the tissue specific roles of argininosuccinate synthase (argininosuccinate synthetase) (EC 6.3.4.5), as the rate-limiting step in the conversion of L-citrulline to L-arginine. Since its discovery, the function of argininosuccinate synthase has been linked almost exclusively to hepatic urea production despite the fact that alternative pathways involving argininosuccinate synthase were defined, such as its role in providing arginine for creatine and for polyamine biosynthesis. However, it was the discovery of nitric oxide that meaningfully extended our understanding of the metabolic importance of non-hepatic argininosuccinate synthase. Indeed, our knowledge of the number of tissues that manage distinct pools of arginine under the control of argininosuccinate synthase has expanded significantly.

Citing Articles

L-Arginine and Nitric Oxide in Vascular Regulation-Experimental Findings in the Context of Blood Donation.

Kurhaluk N, Tkaczenko H Nutrients. 2025; 17(4).

PMID: 40004994 PMC: 11858268. DOI: 10.3390/nu17040665.


Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase.

Alberto-Silva C, Silva B, da Silva J, da Cunha E Silva F, Kodama R, da Silva W Pharmaceuticals (Basel). 2024; 17(7).

PMID: 39065782 PMC: 11279908. DOI: 10.3390/ph17070931.


Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.

Xu L, Zheng X, Yin S, Yang K, Fan Q, Gu Y Invest Ophthalmol Vis Sci. 2024; 65(5):29.

PMID: 38767907 PMC: 11114610. DOI: 10.1167/iovs.65.5.29.


Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages.

Kim D, Kang Y, Jin J, Park M, Kim D, Yoon G Exp Mol Med. 2024; 56(5):1123-1136.

PMID: 38689086 PMC: 11148203. DOI: 10.1038/s12276-024-01214-1.


The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.

Benza R, Grunig E, Sandner P, Stasch J, Simonneau G Eur Respir Rev. 2024; 33(171).

PMID: 38508664 PMC: 10957071. DOI: 10.1183/16000617.0183-2023.


References
1.
Icking A, Matt S, Opitz N, Wiesenthal A, Muller-Esterl W, Schilling K . NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS. J Cell Sci. 2005; 118(Pt 21):5059-69. DOI: 10.1242/jcs.02620. View

2.
Shuttleworth C, Conlon S, Sanders K . Regulation of citrulline recycling in nitric oxide-dependent neurotransmission in the murine proximal colon. Br J Pharmacol. 1997; 120(4):707-13. PMC: 1564508. DOI: 10.1038/sj.bjp.0700949. View

3.
Topal G, Topal J, Brunet A, Walch L, Boucher J, David-Dufilho M . Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells. J Pharmacol Exp Ther. 2006; 318(3):1368-74. DOI: 10.1124/jpet.106.103747. View

4.
Kobayashi K, Jackson M, Tick D, OBrien W, Beaudet A . Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. J Biol Chem. 1990; 265(19):11361-7. View

5.
Delage B, Fennell D, Nicholson L, McNeish I, Lemoine N, Crook T . Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer. 2010; 126(12):2762-72. DOI: 10.1002/ijc.25202. View