DDAH1,2 hydrolyses ADMA to DMA and L-Cit

Stable Identifier
Reaction [transition]
Homo sapiens
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N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays a role in the regulation of nitric oxide generation by catalyzing the hydrolysis an endogenous inhibitor of nitric oxide synthase (NOS), N(omega),N(omega)-dimethyl-L-arginine (ADMA) to dimethylamine (DMA) and L-citrulline (L-Cit) (Forbes et al. 2008, Wang et al. 2009). DDAH2, an isoform of DDAH1 previously thought to catalyze this reaction (Cillero-Pastor et al. 2012) has recently been shown to have no detectable catalytic activity against ADMA under conditions in which DDAH1 is active (Ragavan et al. 2023).

Literature References
PubMed ID Title Journal Year
37296100 A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase

Rubets, E, Jarzebska, N, Suzuki-Yamamoto, T, Chen, Y, Bernhardt, N, Bianconi, E, Macchiarulo, A, Mukhopadhyay, D, Mangoni, AA, Wang, Y, Ruta, L, Tommasi, S, Chau, S, Grottelli, S, Tararova, ND, Ragavan, VN, Spieth, PM, Ryazanskiy, D, Weiss, N, Kimoto, M, Cellini, B, Martens-Lobenhoffer, J, Bornstein, SR, Bode-Böger, SM, Angom, RS, Maas, R, Nair, PC, Hu, X, Rodionov, RN, Lentz, SR

Nat Commun 2023
21898353 Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial protein modulating nitric oxide synthesis in normal human chondrocytes

Oreiro, N, Ruiz-Romero, C, Mateos, J, Blanco, FJ, Cillero-Pastor, B, Fernández-López, C

Arthritis Rheum. 2012
19663506 Developing dual and specific inhibitors of dimethylarginine dimethylaminohydrolase-1 and nitric oxide synthase: toward a targeted polypharmacology to control nitric oxide

Monzingo, AF, Robertus, JD, Wang, Y, Fast, W, Schaller, TH, Hu, S

Biochemistry 2009
18171027 Mechanism of 4-HNE mediated inhibition of hDDAH-1: implications in no regulation

Green-Church, KB, Forbes, SP, Guzman, JE, Parinandi, N, Druhan, LJ, Cardounel, AJ, Zhang, L

Biochemistry 2008
Catalyst Activity

dimethylargininase activity of DDAH1 [cytosol]

Orthologous Events
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