Figure 1. NO-ADMA-DDAH pathway.

Onset of infection in sepsis leads to an up-regulation of inducible nitric oxide synthase (NOS) in response to lipopolysaccharide and pro-inflammatory cytokines. This consequently increases nitric oxide (NO) production, which has a multitude of effects on endothelial, vascular, and immune function. Asymmetric dimethylarginine (ADMA) is produced by the methylation of arginine residues on proteins by the enzyme protein-arginine methyltransferase (PRMT) and metabolized by dimethylarginine dimethylaminohydrolase (DDAH). ADMA competitively inhibits NOS, thereby limiting NO production.