Monomethylarginine

Monomethylarginine, commonly referred to as NG-monomethyl-L-arginine (NMMA), is an endogenous derivative of the amino acid arginine. It arises when protein arginine residues are methylated by protein arginine methyltransferases (PRMTs) and are later released during protein turnover. The biologically active form is the L-enantiomer, and monomethylarginine is detectable in blood plasma, urine, and tissues.

NMMA functions as an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for producing nitric oxide (NO), a key signaling molecule in vascular and nervous systems. It acts as a competitive inhibitor by competing with L-arginine at the NOS active site, thereby reducing NO production. Compared with asymmetric dimethylarginine (ADMA), NMMA is generally considered a weaker inhibitor, but it can contribute to NOS inhibition under physiological conditions.

Metabolism and clearance of NMMA involve the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which hydrolyzes NMMA to citrulline and methylamine. NMMA is also excreted in urine. Its cellular and systemic levels are influenced by renal function and the activity of DDAH, and they occur alongside other methylated arginines such as ADMA and SDMA.

Clinical and research relevance: elevated NMMA levels have been reported in conditions associated with endothelial dysfunction and impaired NO signaling, including hypertension, renal disease, sepsis, and preeclampsia. NMMA is used as a biomarker in some studies, often together with ADMA and SDMA, to assess NOS inhibition status. Measurement is typically performed by specialized analytical methods such as LC-MS/MS. In routine clinical practice, NMMA testing is less common than measurements of ADMA or SDMA.