Nucleotide Synthesis and Degradation

Study Questions




1. Be prepared to identify some nucleotide structures.  What are some tricks that you can use to distinguish among them?


2. Assign the appropriate numbers to the atoms of a purine ring structure and identify the precursor of each of these atoms.

3. Explain what is meant by "chaneling." Using specific examples, explain the purposes that chanelling serves.

4. In bacteria, sulfonamides inhibit nucleic acid biosynthesis.  Explain why this occurs and why it makes sulfonamides useful antibiotics in animals.

5. Calculate the number of ATP equivalents needed for the de novo synthesis of: IMP, AMP, and GMP.  Assume that all of the substrates necessary are available (ex. Gln, a-D-Ribose-Phosphate, etc)


6. Understand the control network for purine synthesis. Explain the biochemistry of the increased uric acid production seen in Lesch-Nyhan Syndrome and in von Gierke’s


7. Identify what compounds contribute atoms to pyrimidine ring synthesis.

8. Know all of the reactions in which PRPP has played a part thus far in the course.

9. Understand the mechanisms that we've seen so far in which a carbanion is stabilized in its transition state during a decarboxylation reaction.

10. Understand the "high points" of the pyrimidine synthesis pathway, especially steps 5 and 6.  I may provide an incomplete pathway and subsequently ask specific questions regarding the pathway.


11. Understand the regulatory scheme for pryimidine nucleotide biosynthesis. Additionally, be prepared to explain the relationship between OMP and PRPP as well as the factors that affect PRPP levels.


12. Understand the regulation of pyrimidine nucleotide biosynthesis and explain the finding of orotic acid in the urine of a person with Orotic Aciduria. Rationalize the use of uridine or cytidine in the treatment of this disease.

13. Explain the control mechanism of Ribonulceotide Reductase (RNR) if given a schematic of the detailed mechanism. 

14. If given a "cartoon" of the R1 and R2 subunits of E. coli RNR, identify the allosteric sites (activity, specificity and hexamerization sites) , location of metal ions, sulfhydryl groups, and Tyr122.


15. Explain the sequence of events in the electron-transfer process from NADPH to a NDP.

16. Understand the "high points" of the mechanism of the Thymidylate Synthase reaction.  If given a schematic, explain specific steps.

17. What are the 3 steps in the formation of dTMP from dUMP? Explain why dUTP is not simply methylated to form dTTP.

18. Understand the catalytic mechanism of Thymidylate Synthase and the regeneration of THF well enough so that you can explain the action of the anti-cancer agents that we discussed.


19. Understand fully the purine catabolic pathway. In particular, know the function of each enzyme so that, if given the structure of a reactant, you could draw the structures of the product(s).


20. How is Ribose-1-Phosphate recycled so as to be available for the formation of PRPP?


21. Understand fully the purine nucleotide cycle and be able to write the overall reaction for this process if given individual steps.


22. Explain the biochemical and subsequent medical consequences of a deficiency of Myoadenylate Deaminase.


23. Explain the biochemical consequences of ADA deficiency and explain them using the purine degradation pathways as a guide.


24. Explain the biochemical consequences of Glucose-6-Phosphatase deficiency that results in gout due to increased production of Uric Acid.


25. Explain how Allopurinol works to decrease Uric Acid excretion.  (I will give you the structures of both Allopurinol and Uric Acid)


26. Compare and contrast the degradation pathways of purines and pyrimidines, making sure to mention whether bases get oxidized or reduced. Explain why pyrimidine nucleotide degradation contributes (to a limited extent) to the energy metabolism of the cell.




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