NUCLIC ACID BIOSYNTHESIS [Autosaved].pptx

IN DEPTH PROCESS OF NUCLIOTIDE BIOSYNTHESIS

1. Difference Between Nucleoside & Nucleotide Pentose sugar N2 Base P Pentose sugar N2 Base Nucleoside Nucleotide

2. N2 Base PURINES PYRAMIDINES Adenine (A) Thymine (T) Guanine (G) Cytosine (C) / Uracil (U)

3. Purines

4. Adenine 6-aminopurine Guanine 2-amino-6-oxypurine

5. Purine Nucleotides Base Ribonucleotides Deoxyribonucleotides Adenine Adenosine Monophosphate ( AMP ) / Adenylic acid 2’deoxy-Adenosine Monophosphate (2’dAMP)/2’ Deoxy adenylic Acid Guanine Guanosine Monophosphate ( GMP ) / Guanylic acid 2’deoxy-Guanosine Monophosphate (2’dGMP)/2’ Deoxy Guanylic Acid

6. Purine Biosynthesis : Overview De Novo Synthesis Phosphoribosylation of Purines Phosphorylation of Purine Nucleosides

7. Hexose Mono Phosphate (HMP) Pathway Ribose – 5 Phosphate Inosine Monophosphate (IMP) AMP GMP ADP GDP ATP GTP dADP , dGDP

8. 1 2 3 4 5 6 7 8 N N N N 9 C C C C C N - Aspartate C – Formal THFA & 9. N - Glutamine 8. C – Methenyl THFA

9. Purine Ring – Sources

10. Overview : Purine Biosynthesis : Steps STEP ADDED ATOM PRODUCT 1 ATP Phosphoribosyl pyrophosphate 2 Glutamine N9 Phosphoribosyl amine 3 Glycine, ATP C4,C5,N7 Glycinamide Ribosyl 5-P 4 Methenyl-THFA C8 – Formyl Group Formal Glycinamide Ribosyl 5-P 5 Glutamine, ATP N3 Formal Glycinamidine Ribosyl 5-P 6 ATP Ring Closure (Imidazole) Aminoimidazole Ribosyl 5-P

11. STEP ADDED ATOM PRODUCT 7 Carbon dioxide C6 Aminoimidazole Carboxylate Ribosyl 5-P 8 Aspartic Acid, ATP N1 Aminoimidazole Succinyl Carboxamide Ribosyl - P 9 - Fumarate removed Aminoimidazole Carboxamide Ribosyl 5- P 10 Formyl - THFA C2 – Formyl group Formamino imidazole carboxamide Ribosyl 5-P 11 - Ring closure IMP- Inosine Monophosphate

12. Purine Biosynthesis : Elaboration Step - 1 1. Synthesis of 5 – Phosphoribosyl Pyrophosphate 1 ATP AMP PRPP Synthetase P-O-CH2 H H OH P-O-CH2 H H O-P-O-P α- D-Ribose 5-Phosphate 5 – Phosphoribosyl Pyrophosphate (PRPP)

13. Purine Biosynthesis : Elaboration Step - 2 2. Synthesis of 5 – Phosphoribosyl amine 2 H2O + Glutamine PPi + Glutamate PRPP Synthetase P-O-CH2 H H O-P-O-P P-O-CH2 NH2 H H 5 – Phosphoribosyl Pyrophosphate (PRPP) 5 – Phosphoribosyl amine

14. Purine Biosynthesis : Elaboration Step - 3 3. Synthesis of 5 – Glycinamide ribosyl 5-P 3 ATP + Glycine ADP + Pi Synthetase P-O-CH2 NH2 H H P-O-CH2 NH-CO-CH2NH2 H H 5 – Phosphoribosyl amine Glycinamide ribosyl 5-P

15. Purine Biosynthesis : Elaboration Step - 4 4. Synthesis of 5 – Formylglycinamide ribosyl 5-P 4 N5,N10 Methenyl THF ADP + Pi Formyl transferase Glycinamide ribosyl 5-P Formyl glycinamide ribosyl 5-P

16. Purine Biosynthesis : Elaboration Step - 5 5. Synthesis of Formyl glycinamidine ribosyl 5-P 5 ATP + Glutamine ADP+Pi + Glutamate Synthetase Formyl glycinamide ribosyl 5-P Formyl glycinamidine ribosyl 5-P

17. Purine Biosynthesis : Elaboration Step - 6 6. Synthesis of Aminoimidazole Ribosyl 5-P 6 ATP ADP+Pi Synthatase Formyl glycinamidine ribosyl 5-P Aminoimidazole Ribosyl 5-P H2O

18. Purine Biosynthesis : Elaboration Step - 7 7. Synthesis of Aminoimidazole Carboxylate Ribosyl 5-P 7 CO2 Carboxylase Aminoimidazole Ribosyl 5-P Aminoimidazole Carboxylate Ribosyl 5-P

19. Purine Biosynthesis : Elaboration Step - 8 8. Synthesis of Aminoimidazole Succinyl Carboxamide Ribosyl - P 7 ATP + Aspartate Synthetase Aminoimidazole Carboxylate Ribosyl 5-P Aminoimidazole Succinyl Carboxamide Ribosyl - P ADP + Pi

20. Purine Biosynthesis : Elaboration Step - 9 9. Synthesis of Aminoimidazole Carboxamide Ribosyl 5- P 7 Fumarate Adenosuccinate lyase Aminoimidazole Succinyl Carboxamide Ribosyl - P Aminoimidazole Carboxamide Ribosyl 5- P

21. Purine Biosynthesis : Elaboration Step - 10 10. Synthesis of Formaminoimidazole carboxamide Ribosyl 5-P N10 Formyl THF Formyl transferase Aminoimidazole Carboxamide Ribosyl 5- P Formaminoimidazole carboxamide Ribosyl 5-P THF

22. Purine Biosynthesis : Elaboration Step - 11 11. Synthesis of IMP- Inosine Monophosphate Cyclohydrolase Formaminoimidazole carboxamide Ribosyl 5-P IMP- Inosine Monophosphate H2O

23. Synthesis of AMP From IMP INOSINE MONOPHOSPHATE ADENOSINE MONOPHOSPHATE (AMP) ADENYLSUCCINATE Aspartate + GDP GDP + Pi Fumarate Adenylsuccinase Adenylsuccinate synthetase

24. INOSINE MONOPHOSPHATE GUANOSINE MONOPHOSPHATE (GMP) XANTHOSINE MONOPHOSPHATE GMP Synthetase IMP Dehydrogenase Synthesis of GMP From IMP GMP GDP GTP ATP ADP ADP ATP GDP Kinase GMP Kinase

25. AMP ADP ATP ATP ADP ADP ATP ADP Kinase AMP Kinase GMP GDP GTP ATP ADP ADP ATP GDP Kinase GMP Kinase