Simplified scheme of L-arginine pathways in mammalian host cells.

L-arginine is a crossroad for multiple pathways since it is the common substrate of arginase and NOS that catalyzes the production of L-ornithine, L-citrulline and NO, respectively. ADMA, a product of the proteolysis of methylated proteins by PRMT-1, is a potent inhibitor of NOS. Its concentration is regulated by DDAH that catalyzes the production of L-citrulline and dimethylamine. L-ornithine and L-glutamate serve as precursors of polyamines and glutathione. These two metabolites will be further utilized by the trypanosomes for the synthesis of trypanothione, an essential element protecting the parasites from free radicals. Abbreviations: NO, nitric oxide; NOS, nitric oxide synthase; ADMA, asymmetric dimethylarginine; DDAH, NG,NG-dimethylarginine dimethylaminohydrolase; PRMT-1, Protein arginine N-methyltransferase 1; GABA, γ-aminobutyric acid.