Arginine is transported into mammalian macrophages by amino acid transporters (SLC7A1/7A2/7A5/7A7, SLC3A2), then metabolized by either inducible NO synthase (iNOS) into NO and citrulline, or arginase into ornithine and urea. Citrulline can feed back into arginine synthesis via ASS1 and inducible ASL. Citrulline, polyamines or proline and glutamate can be generated from ornithine via ornithine transcarbamylase (OTC), ornithine decarboxylase (ODC) or ornithine aminotransferase (OAT), respectively. The iNOS cofactor, THB, is generated by GTP via GCH1, PTS, and SPR respectively, and is a rate-limiting step in the production of NO.