Dimethylarginine dimethylaminohydrolase 1 (DDAH1)

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an intracellular hydrolase that catalyzes the hydrolysis of methylated arginines such as asymmetric dimethylarginine (ADMA) and N-monomethylarginine (NMMA), converting them to L-citrulline and methylamines. DDAH1's major physiological role is to regulate nitric oxide bioavailability by metabolizing inhibitors of nitric oxide synthase, principally ADMA, thus playing a critical part in endothelial function, vascular tone, angiogenesis, cell proliferation, and wound healing. The structure of DDAH1 includes a five-stranded propeller domain characteristic of the L-arginine/glycine amidinotransferase superfamily. Zinc can endogenously bind and competitively inhibit the enzyme by coordinating at the active site. Dysregulation of DDAH1 is implicated in cardiovascular diseases, certain cancers, and impaired tissue repair via its modulation of the NO pathway and related cell signaling mechanisms. The enzyme is recognized as both a mechanistic biomarker and a therapeutic target in these contexts.

Other names

DDAH1DDAHDDAH-1Dimethylargininine dimethylaminohydrolase 1NG,NG-dimethylarginine dimethylaminohydrolaseDimethylargininase-1HEL-S-16Epididymis secretory protein Li 16

Enzyme inhibitors block DDAH1's activity, leading to increased ADMA and reduced nitric oxide bioavailability. Modulators decrease ADMA levels, promoting nitric oxide synthesis, endothelial health, and angiogenesis. Zinc binds to the DDAH1 active site and inhibits catalytic activity.