Figure 5.

Schematic representation of L-arginine metabolism in Leishmania-infected macrophages. The uptake of L-arginine in macrophages occurs via cationic transporter (CAT). In infected-macrophages, depending on L-arginine availability can direct to Nitric Oxide Synthase 2 (NOS2) expression and nitric oxide (NO) and citrulline production, or can direct to arginase 1 (ARG1) expression and ornithine production. Further, ornithine supplies proline, glutamate and putrescine production by ornithine cyclodeaminase (OCD), ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC), respectively. Putrescine and S-adenosyl-methionine are the substrate for spermidine synthase (SpdS) and spermine synthase (SpmS) producing spermidine and spermine, respectively. In infected macrophages, L-arginine transport can occur by polyamine transporter (POT) and other unknown transporters (?). The uptake of L-arginine in Leishmania occurs via amino acid permease 3 (AAP3) and depending on L-arginine availability can direct to nitric oxide synthase-like (NOS) expression and NO and citrulline production, or can direct to arginase (ARG) expression and ornithine production. Ornithine supplies proline, glutamate, and putrescine production by OCD, OAT, and ODC, respectively. Putrescine is the substrate for SpdS and SpmS producing spermidine and spermine, respectively. Spermidine is the substrate to produces gluthationyl spermidine and subsequently tripanothine. Blue arrows represent the higher levels of metabolites found in infected-macrophages compared to uninfected.