1. BIOC/DENT/PHCY 230 LECTURE 6

3. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)

4. Building blocks for nucleotides

5. Two classes of bases

6. Two types of ribose

7. Synthesis of nucleotides o nucleotide bases can be recycled or synthesised de novo o purine bases are synthesised on ribose o pyrimidine bases are synthesised independent of ribose

8. AMP Synthesis of PRPP o PRPP contributes ribose phosphate to nucleotides o formation catalysed by PRPP synthetase PRPP synthetase is allosterically inhibited by AMP, ADP and GDP.

9. De novo purine synthesis Glutamine donates an amide to initiate purine synthesis A whole glycine is added to the nitrogen

10. The coenzyme tetrahydrofolate donates a formyl group Glutamine donates a second amide

11. Imidazole ring is closed in an energy dependent reaction

12. Aspartate is added in an energy dependent reaction This is analogous to the urea cycle

14. Tetrahydrofolate donates a second formyl group Ring closure

15. Origins of purine base

16. IMP can be converted to GMP and AMP

17. De novo pyrimidine synthesis The pyrimidine base is synthesised before being attached to ribose

18. ring closure and oxidation

19. Ribose is now added via PRPP

20. UMP can be used to synthesise CTP

22. Origins of pyrimidine base

23. purines pyrimidines Base synthesis on ribose free Amino acids gln(2), asp, asp gly Other molecules formate(2)carbamoyl HCO 3 - phosphate ATP 5 2 (AMP,GMP) (UMP) CMP gln 3 Comparison of purine and pyrimidine biosynthesis

24. Ribonucleotides are used as precursors for deoxyribonucleotides ATPdATP GTPdGTP CTPdCTP UTPdUTP Ribonucleotide reductase

25. Thymidine nucleotides are derived from dUMP Tetrahydrofolate donates a methyl group

26. Degradation of pyrimidine nucleotides CTPUTP  -alanine, NH 3, CO 2

27. Degradation of purine nucleotides

28. Free ammonia is also produced in muscle o during severe muscle activity ATPADP + P i 2ADPATP + AMP AMPIMP + NH 4 + AMP deaminase

29. Degradation of purine nucleotides

30. GOUT o uric acid is quite insoluble o excess uric acid can crystallise in joints o gout can be treated with allopurinol o allopurinol is a competitive inhibitor of xanthine oxidase

32. The take home message o nucleotides have a number of functions o they can be synthesised de novo if required o some steps are analogous with the urea cycle o amino acids provide many of the components o synthesis is regulated by the concentrations of various nucleotides o synthesis is energetically expensive o the degradation of excess purines can cause gout