While tumor cells with CPS1 overexpression generate high amounts of carbamoyl phosphate that may translocate into the cytoplasm and then support CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase)-mediated de novo pyrimidine synthesis [27,31,48], the reduction of CPS1 in HCC rewires ammonia metabolism by recycling ammonia to glutamine for the initiation of de novo pyrimidine biosynthesis [28,49]. This evidence concerns the gene CPS1 and hepatocellular carcinoma.