N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1)

N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a critical hydrolytic enzyme that regulates the bioavailability of nitric oxide (NO) by metabolizing endogenous nitric oxide synthase (NOS) inhibitors, specifically asymmetric dimethylarginine (ADMA) and N(G)-monomethyl-L-arginine (L-NMMA) [1, 2, 4]. By maintaining low cellular and systemic levels of these inhibitors, DDAH1 ensures proper endothelial function, vascular homeostasis, and the regulation of blood pressure [8, 15, 16]. In cardiovascular and renal diseases, such as hypertension, congestive heart failure, and chronic kidney disease, DDAH1 activity is often impaired, leading to the accumulation of ADMA and subsequent reduction in NO signaling [1, 3, 10]. Conversely, DDAH1 is frequently overexpressed in various malignancies, including breast, prostate, and gastric cancers, where it promotes tumor growth, metastasis, and pathological angiogenesis by increasing local NO production [4, 9, 17]. This dual role makes DDAH1 a versatile therapeutic target: DDAH1 inhibitors are being developed to suppress tumor progression and manage excessive NO in septic shock, while DDAH1 activators or expression enhancers, such as farnesoid X receptor (FXR) agonists and statins, are explored for cardiovascular protection [5, 10, 12]. Monitoring ADMA levels and the L-arginine/ADMA ratio serves as a key clinical biomarker for assessing DDAH1 function and associated cardiovascular risk [1, 15].

Other names

DDAH-1Dimethylarginine dimethylaminohydrolase 1Dimethylargininase-1NG,NG-dimethylarginine dimethylaminohydrolase 1DDAHI

DDAH1 regulates nitric oxide (NO) production by hydrolyzing asymmetric dimethylarginine (ADMA) and N(G)-monomethyl-L-arginine (L-NMMA), which are competitive endogenous inhibitors of nitric oxide synthase (NOS) [1, 2, 4]. Pharmacological inhibitors of DDAH1 increase ADMA levels to reduce excessive NO production in conditions like cancer or septic shock [5, 9]. Conversely, activators or inducers of DDAH1 expression (such as FXR agonists) lower ADMA levels to restore NO bioavailability and improve endothelial function in cardiovascular and renal diseases [1, 10].