ASS1 tetramer:NMRAL1 dimer:NADPH transforms L-Asp and L-Cit to ARSUA

Stable Identifier
Reaction [transition]
Homo sapiens
ATP + aspartate + citrulline <=> argininosuccinate + AMP + pyrophosphate
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Cytosolic argininosuccinate synthase (ASS1 tetramer) catalyzes the reaction of aspartate (L-Asp), citrulline (L-Cit), and ATP to form argininosuccinate (ARSUA), AMP, and pyrophosphate (PPi). The function of the human enzyme in vivo is inferred from the hypercitrullinemia observed in patients with defective forms of the enzyme (e.g., Engel et al. 2009). The enzyme is active as a homotetramer (O'Brien 1980; Karlberg et al. 2008) and binds NmrA-like family domain-containing protein 1 (NMRAL1). NMRAL1 is a redox sensor protein that can undergo restructuring and subcellular redistribution in response to changes in intracellular NADPH/NADP+ levels. Under normal NADPH levels, it can form an asymmetrical dimer with one subunit occupied by one NADPH molecule, hiding the binding site for ASS1 thus impairing its activity and reducing the production of nitric oxide (Zheng et al. 2007, Zhao et al. 2008).

Literature References
PubMed ID Title Journal Year
18263583 An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability

Zheng, X, Li, Y, Li, H, Luo, M, Zhao, Y, Zhang, J, Ren, J

J. Biol. Chem. 2008
18323623 Structure of human argininosuccinate synthetase

Uppenberg, J, Holmberg-Schiavone, L, Flores, A, Hammarström, M, Högbom, M, Collins, R, Karlberg, T, van den Berg, S

Acta Crystallogr D Biol Crystallogr 2008
19006241 Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene

Häberle, J, Engel, K, Höhne, W

Hum Mutat 2009
518841 Isolation and characterization of argininosuccinate synthetase from human liver.

O'Brien, WE

Biochemistry 1980
17496144 Restructuring of the dinucleotide-binding fold in an NADP(H) sensor protein

Zheng, X, Dai, X, Lu, F, Luo, M, Yao, D, Gu, X, Chen, Q, Liu, X, Zhang, C, Zhao, Y, Yu, Q

Proc. Natl. Acad. Sci. U.S.A. 2007
Catalyst Activity

argininosuccinate synthase activity of ASS1 tetramer:NMRAL1 dimer:NADPH [cytosol]

Orthologous Events
Cross References
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