Trichinella spiralis and Trichinella pseudospiralis: developmental patterns of enzymes involved in thymidylate biosynthesis and pyrimidine salvage

Thymidylate synthase, dihydrofolate reductase and dUTPase specific activiti es were found to remain at a high and constant level in crude extracts from adult worms of Trichinella spiralis, as well as from muscle larvae of both Trichinella spiralis (isolated 1-24 months after infection) and Trichinell a pseudospiralis (isolated 5.5-13 months after infection). The results obta ined with Trichinella pseudospiralis muscle larvae isolated with the use of pepsin did not differ from those obtained when pepsin was not used. No thy midine kinase activity could be detected in muscle larvae of either species and thymidine phosphorylase could be found only in T. pseudospiralis larva e isolated without the use of pepsin. Muscle larvae of both species contain ed orotidylate phosphoribosyl transferase activity, pointing to a possibili ty of 5-fluorouracil activation. Uridine phosphorylase, another enzyme invo lved in 5-fluorouracil anabolism, was also present in T. pseudospiralis mus cle larvae. Results of comparative studies on inhibition of purified T. spi ralis and rat thymidylate synthases by substrate (4-thio-5-fluoro-dUMP, 2-t hio-5-fluoro-dCMP and N-4-hydroxy-dCMP) and cofactor (ZD 9331) analogues in dicated only dUMP analogues to show feeble selectivity towards the parasite enzyme. A hypothesis is discussed, assuming high expression of thymidylate synthase in muscle larvae to be connected with their cells being arrested in the cell cycle.