Dimethylargininase

Dimethylargininase is an enzyme that plays a crucial role in the metabolism of nitric oxide. It is responsible for the hydrolysis of N,N-dimethyl-L-arginine (ADMA) and N-monomethyl-L-arginine (L-NMMA), which are natural inhibitors of nitric oxide synthase (NOS).

Function

Dimethylargininase exists in two isoforms, dimethylargininase 1 (DDAH1) and dimethylargininase 2 (DDAH2). Both isoforms are involved in the regulation of nitric oxide production by metabolizing the methylarginines ADMA and L-NMMA.

ADMA and L-NMMA are derived from the protein turnover of methylated arginine residues. They inhibit NOS by competing with L-arginine for the active site of the enzyme. By metabolizing these inhibitors, dimethylargininase helps to maintain the production of nitric oxide, which is a key regulator of vascular tone, platelet aggregation, and neurotransmission.

Clinical significance

Abnormal dimethylargininase activity has been associated with various pathological conditions, including cardiovascular diseases, renal disease, and diabetes. Elevated levels of ADMA, resulting from reduced dimethylargininase activity, can lead to decreased nitric oxide production and subsequent endothelial dysfunction, which is a key factor in the development of atherosclerosis and hypertension.

See also

• Nitric oxide synthase
• Arginine
• Atherosclerosis
• Hypertension