fig4

Figure 4. Pyrimidine synthesis and one carbon metabolism. Several enzymes involved in pyrimidine synthesis and one carbon metabolism are overexpressed in thyroid cancer. Bold arrows indicate increased metabolite flux. Beige circles indicate enzymes not shown to be aberrantly expressed in TC. Red circles display overexpressed enzymes in TC. Inhibitors are outlined in red circles with conjoining red inhibitor (T) bars. Inhibitors in bold have demonstrated efficacy in TC models. Green arrows indicate allosteric regulation of the indicated enzyme. Enzyme/transporter/metabolite key: 1. PRPP synthetase; 2. Carbamoyl-phosphate synthetase 2; 3. Aspartate transcarbamoylase; 4. Dihydroorotase; 5. Dihydroorotate dehydrogenase; 6. Orotate phosphoribosyltransferase; 7. Orotidine-5′-phosphate decarboxylase; 8. Uridine-cytidine kinase 2; 9. Nucleoside diphosphate kinase A; 10. CTP synthetase; 11. Ribonucleotide reductase; 12. dUTP diphosphatase; 13. Thymidylate synthase; 14. Deoxythymidylate kinase; 15. Phosphoglycerate dehydrogenase; 16. Phosphoserine aminotransferase 1; 17. Phosphoserine phosphatase; 18. Serine hydroxymethyltransferase 1; 19. Dihydrofolate reductase. PKM2: Pyruvate kinase 2.