Dimethylarginine dimethylaminohydrolase (DDAH)

Dimethylarginine dimethylaminohydrolase is a highly conserved enzyme present in two main isoforms (DDAH1 and DDAH2), both of which metabolize methylated arginines, notably ADMA and MMA, which are endogenous inhibitors of nitric oxide synthase (NOS). By hydrolyzing these methylarginines, DDAH regulates NO production, affecting vascular tone, angiogenesis, and cellular signaling. DDAH is broadly expressed in tissues such as the brain, kidney, liver, heart, and immune cells, and plays a significant role in the pathophysiology of cardiovascular diseases and cancer through its modulation of NO-mediated processes. Therapeutic interest focuses on DDAH as a target for conditions with excessive or dysfunctional NO signaling.

Other names

DimethylargininaseN(G),N(G)-dimethylarginine dimethylaminohydrolaseDDAHDDAH-1DDAH-2

Inhibitors: Block hydrolysis of ADMA/MMA, increase their levels, reduce NO synthesis. Activators (not widely reported in clinical use): Would increase ADMA clearance, potentially increase NO production