NUCLEOTIDES

1. Nucleoproteins M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

2. Nucleoproteins are conjugated proteins (basic proteins + nucleic acids) Nucleic acids – DNA and RNA DNA is the chemical basis of heredity. Sir diagram

3. Nucleoside and nucleotide Nucleic acids are polymers of mononucleotides held by 3' and 5' phosphodiester bonds Nucleoside --- Base + Sugar Nucleotide --- Base + sugar + phosphate (phosphorylated nucleoside ).

4. BASES They are nitrogenous heterocyclic compounds TWO Types : Purines Pyrimidines . Adenine .Cytosine . Guanine .Thymine .Uracil Purines are numbered in anticlockwisedirection in pyrimidine ring and clockwise direction in imidazole ring. Pyrimidines are numbered in clockwisedirection

5. NUMBERING OF PURINE AND PYRIMIDINE RINGS

6. PURINE BASES ADENINE - 6 – amino purineGUANINE – 2-amino 6 oxy purine 6 6 2 9

7. PYRIMIDINE BASES • CYTOSINE (both DNA and RNA) • 2-oxy 4 amino pyrimidine 4 2

8. THYMINE (DNA) 2,4 - dioxy 5methylpyrimidine 4 5 2

9. URACIL (RNA) 2,4 -dioxypyrimidine 4 2

10. SUGARS D - RIBOSED –2- deoxy ribose

11. Numerals with prime ( ' ) distinguish carbon atoms of sugar from those of heterocycle nitrogenous base. The sugar ( c1 ) is linked to base via a beta – N – glycosidic bond , almost always to N-1 of pyrimidine and N-9 of purine.

12. The hydroxyl groups of adenosine are esterified with • phosphate to produce 3 ' or 5' monophophate. • 5' OH is commonly esterified ,hence 5' omitted. • Adenosine 5' monophosphate ------- AMP(adenylate) • Addition of 2nd or 3 rd phosphate to nucleoside results • in nucleoside diphosphate and triphosphate • respectively.

13. Base + Sugar Nucleoside Adenine + Ribose Adenosine Guanine + Ribose Guanosine Cytosine + Ribose Cytidine Uracil + Ribose Uridine Adenine + Deoxyribose Deoxy Adenosine Guanine + Deoxyribose Deoxy Guanosine Cytosine + Deoxyribose Deoxy Cytidine Thymine + Deoxyribose Deoxy Thymidine

14. Principal bases ,nucleosides and nucleotides

15. Nucleoside + PhosphateNucleotide Adenosine + Phosphate Adenylate(AMP) Guanosine + Phosphate Guanylate(GMP) Cytidine + Phosphate Cytidylate(CMP) Uridine + Phosphate Uridylate(UMP)

16. deoxyNucleoside + Phosphate deoxyNucleotide Deoxyadenosine + phosphate - deoxyadenylate(dAMP) Deoxy guanosine+phosphate - deoxyguanylate(dGMP) Deoxycytidine+ phosphate --- deoxycytidylate(dCMP) Deoxythymidine +phosphate - deoxythymidylate(dTMP)

17. Minor/unusual bases • Specific DNAs and RNAs of both prokaryotes and eukaryotes • contain smaller amounts of additional bases termed minor or • unusual bases. • These bases are functionally important and hence not of minor Physiologic significance . • They are widely distributed in nature.

18. Minor bases – cont.. • 5-methylcytosine – present in both bacterial and • human DNA • 2. Mono and di methylated adenine present in • mammalian RNA. • 3. Di methyl guanine present in mRNA. • 4. Various derived bases in tRNA s.eg: pseudouridine. • 5- hydroxy methyl cytosine of bacteriophage DNA occur in • bacteria and viral nucleic acids.

19. Functions of minor bases: • Small quantities of unusual bases form structural • components of DNA and RNA. • 2.They regulate the half –life of RNAs • 3. The presence of specific methylated nucleotide • bases protect the human DNA from the DNAases • arising from viral /bacterial pathogens.

20. Plants: Methylated bases include xanthine derivatives • Caffeine of coffee -- 1,3,7 – trimethyl xanthine • Theobromine of cocoa -- 3,7 – dimethyl xanthine • Theophylline of tea -- 1, 7 – dimethyl xanthine

21. Classification of nucleotides • Adenosine nucleotides eg: ATP, ADP,AMP, cyclic AMP • 2.Guanosine nucleotides eg: GTP, GDP , GMP , • cyclic GMP • 3.Cytidine nucleotides eg; CTP,CDP,CMP ,CDP-choline • 4.Uridine nucleotides eg:UTP,UDP,UMP ,UDP – glucose

22. Functions of Nucleotides: • Building blocks of nucleic acids – DNA , RNA. • Involved in energy reactions of the cell eg: ATP • Form part of many coenzymes of B-complex • vitamins like FAD,NAD,NADP

23. UDP-Glucose is involved in glycogen synthesis. • UDP- glucuronic acid is involved in conjugation reactions eg: bilirubin. • CTP is required for synthesis of phosphoglycerides and sphingomyelin • Regulatory nucleotides/second messengers eg: Cyclic AMP , cyclic GMP.

24. ATP – Adenosine triphosphate. – Major biologic transducer of free energy. – Intra cellular conc is 1 mmol/L. – Most abundant free nucleotide in mammalian cells.

25. cAMP • Cyclic adenosine 3’,5’- monophosphate. • Formed from ATP, catalyzed by adenylyl cyclase. • Second messenger. • IC conc is 1 nmol/L. • Its level is maintained by interaction of adenylyl cyclase & cAMP phosphodiesterase.

27. Adenosine 3’-phosphate -5’-phospho sulfate (PAPS) • Active sulfate • Sulfate donor for formation of sulfated proteoglycans, urinary metabolism of drug excreted as sulfate conjugates.

29. Synthetic analogs of purine/ pyrimidine nucleotides • Mechanism Of action : • Inhibition of specific enzymes essential for • nucleic acid synthesis. • Incorporation of metabolites of the drug into nucleic acids that affect base pairing , essential for accurate transfer of information.

30. USES: Chemotherapeutic agents for cancer ,AIDS and suppressors of immune rejection in organ transplantation. Eg: 1. Allopurinol used in gout – inhibits xanthine oxidase 2.Cytarabine used in cancer and viral infections. 3 . Azathiopurine used in organ transplantation 4. 5- iodo – deoxy uridine used in herpetic keratitis

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