Thymidylate synthase (ThS) is such an important enzyme and we give it so little credit in the pursuit of gloryfying Pyruvate Kinase, et al. ThS is inhibited by 5-fluorouracil (5-FU), an anticancer drug. ThS produces dTMP (as you can see in the graph) from dUMP. The small d is for the reduced form of UMP, which is made by another important enzyme Ribonucleotide Reductase (UMP to dUMP). And, where does the UMP come from? A sexy molecule calledOrotic acid.
Inability to convert orotic acid to UMP produces failure to thrive in the neonatal period, no hyperammonemia (which distinguishes it from OTC deficiency) and … the almost always forgotten megaloblastic anemia. Of course, increased orotic acid as well. So, orotic acidemia, in three words:
- Failure to thrive
- Megaloblastic anemia that doesn’t respond to vit B12 supplementation (or folic acid)
- No hyperammonemia