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

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

Stable Identifier

R-HSA-70577

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

ATP + aspartate + citrulline <=> argininosuccinate + AMP + pyrophosphate

ReviewStatus

5/5

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

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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