1. Nucleotides

2. BIOMEDICAL IMPORTANCE Building blocks of nucleic acids Part of many coenzymes Donors of – Phosphoryl groups (eg, ATP or GTP) – Sugars (eg,UDP- or GDP-sugars) – Lipid (eg, CDP-acylglycerol) Regulatory nucleotides – cAMP and cGMP Control of oxidative phosphorylation – by ADP Allosteric regulation of enzyme activity – by ATP, AMP, and CTP

3. BIOMEDICAL IMPORTANCE For therapy – Chemotherapy of cancer and AIDS – Suppressors of the immune response during organ transplantation

4. Classification PURINES PYRIMIDINES NUCLEOSIDES NUCLEOTIDES

6. Tautomerism of the oxo and amino keto-enol and amine-imine tautomerism

7. Nucleoside – Diphosphates – Triphosphates The sugar moiety – D-ribose or 2-deoxy-Dribose

8. Nucleoside triphosphates – have high group transfer potential Participate in covalent bond syntheses. Cyclic phosphodiesters – cAMP and cGMP Intracellular second messengers

9. Ribonucleosides

11. Additional phosphoryl groups linked by acid anhydride bonds

12. The syn and anti conformers of adenosine differ with respect to orientation about the N-glycosidic bond.

13. Bases, nucleosides, & nucleotides.

16. Nucleic Acids Also Contain Additional Bases 5-methylcytosine 5-hydroxymethylcytosine Mono- and di-N-methylated adenine & guanine – Mammalian messenger RNAs

17. uncommon naturally occurring pyrimidines and purines.

19. Function – Oligonucleotide recognition – Regulating the half-lives of RNAs Free nucleotides – Hypoxanthine, xanthine, and uric acid – Intermediates in the catabolism

22. Posttranscriptional modification Pseudouridine (Ψ) Methylation by S-adenosylmethionine of a UMP of preformed tRNA forms TMP

24. Nucleotides Serve Diverse Physiologic Functions Protein synthesis Nucleic acid synthesis Regulatory cascades Signal transduction pathways

25. Physiologic functions As precursors of nucleic acids Transducer of free energy – ATP The second messenger – cAMP Adenosine 3′-phosphate-5′-phosphosulfate Methyl group donor

27. 3′-phosphate-5′-phosphosulfate (PAPS)

28. S-Adenosylmethionine

29. Uridine diphosphate glucose (UDPGlc).

30. Energy source for protein synthesis – GTP UDP-sugar derivatives – Sugar epimerizations – Biosynthesis of glycogen, glucosyl disaccharides, and the oligosaccharides of glycoproteins and proteoglycans

31. UDP-glucuronic acid. – Conjugation Bilirubin Drugs CTP – Biosynthesis of phosphoglycerides – Sphingomyelin Coenzymes

32. Many coenzymes and related compounds are derivatives of adenosine monophosphate.

34. Flavin adenine dinucleotide (FAD).

35. Nicotinamide adenine dinucleotide (NAD). * Shows the site of phosphorylation in NADP.

36. * Shows the site of acylation by fatty acids.

37. Nucleotides Are Polyfunctional Acids Nucleotides Absorb Ultraviolet Light – Close to 260 nm

38. SYNTHETIC NUCLEOTIDE ANALOGS ARE USED IN CHEMOTHERAPY Altered in – Heterocyclic ring – The sugar moiety Inhibition of enzymes – Treatment of hyperuricemia Incorporation into nucleic acids Suppress immunologic rejection – Organ transplantation

42. POLYNUCLEOTIDES Linked by a 3′ → 5′ phosphodiester bond to form the “backbone” of RNA and DNA RNAs are far less stable than DNA Polynucleotides Are Directional Macromolecule – “5′- end” or the “3′- end” – the 5′- end is at the left

43. Polynucleotides Have Primary Structure Base sequence – Compact notation pGpGpApTpCpA GGATCA

44. DNA Contains Four Deoxynucleotides

46. Double-stranded DNA

47. Formation of hydrogen bonds between complementary bases in double-stranded DNA

48. Base pairing

49. Supercoiling of DNA. DNA Exists in Relaxed & Supercoiled Forms

50. Negative and positive supercoils.

52. extent of DNA packaging in metaphase chromosomes

55. Important structural elements of a yeast chromosome

57. One of the hallmarks of living organisms is their ability to reproduce. DNA contains the genetic information

58. The interrelationship of DNA,RNA & Protein