Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases

Methylarginines inhibit nitric oxide synthases (NOS). Cellular concentratio ns of methylarginines are determined in part by the activity of dimethylarg inine dimethylaminohydrolase (DDAH; EC 3.5.3.18). We have cloned human DDAH and identified and expressed a second novel DDAH isoform (DDAH I and II re spectively). DDAH I predominates in tissues that express neuronal NOS. DDAH II predominates in tissues expressing endothelial NOS. These results stren gthen the hypothesis that methylarginine concentration is actively regulate d and identify molecular targets for the tissue and cell-specific regulatio n of methylarginine concentration.