Fig. 2

Methylarginine-mediated nitric oxide synthase inhibition. Representative image of the synthesis and regulation of ADMA. Protein Arginine Methyl Transferases (PRMT) catalyse the methylation of arginine containing protein residues to ADMA and SDMA which are released upon proteolysis. ADMA and SDMA are transported via the y⁺ cationic amino acid transporter into and out of the circulation. ADMA is metabolised by the two isoforms of dimethylarginine dimethylaminohydrolase (DDAH) in a wide range of tissues. ADMA acts intracellularly to inhibit nitric oxide synthase (NOS). ADMA is largely metabolised by DDAH to dimethylamine (DMA), a small amount is cleared unchanged through the kidney. nb. L-NMMA (monomethylarginine) is considered to have the same synthetic pathway, activity, metabolism and clearance as ADMA but is present in only 10% of the concentration