fig1

Figure 1. Urea and citrulline-NO cycles with connections to arginine deprivation by ADI-PEG20. Within the mitochondria, CPS1 incorporates ammonia into carbamoyl phosphate. OTC then condenses carbamoyl phosphate with ornithine, forming citrulline. In the cytoplasm, ASS1 catalyzes the condensation of aspartate with citrulline to form argininosuccinate. ASL cleaves argininosuccinate into fumarate and arginine. Arginine is hydrolyzed into ornithine and urea by ARG1, completing the cycle. Alternatively, NOS can hydrolyze arginine to regenerate citrulline while producing NO. ADI-PEG20 degrades arginine to citrulline and ammonia extracellularly. Citrulline can then be imported and converted to arginine by ASS1 and ASL. ADI-PEG20: PEGylated arginine deiminase; CPS1: carbamoyl phosphate synthetase I; OTC: ornithine transcarbamoylase; ASS1: argininosuccinate synthetase 1; ASL: argininosuccinate lyase; ARG1: arginase 1; NOS: nitric oxide synthase; NO: nitric oxide;