Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high-throughput chemical screening.

ABSTRACT: Nitric oxide (NO) is a potent signaling molecule that needs to be tightly regulated to maintain metabolic and cardiovascular homeostasis. The nitric oxide synthase (NOS)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is central to this regulation. Specifically, the small-molecule ADMA competitively inhibits NOS, thus lowering NO levels. The majority of ADMA is physiologically metabolized by DDAH, thus maintaining NO levels at a physiological concentration. However, under pathophysiological conditions, DDAH activity is impaired, in part as a result of its sensitivity to oxidative stress. Therefore, the application of high-throughput chemical screening for the discovery of small molecules that could restore or enhance DDAH activity might have signif

SUBMITTER: Ghebremariam YT 

PROVIDER: S-EPMC3606823 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature