Nucleotide

Nucleotide chemistry

1. NUCLEOTIDE CHEMISTRY Dr. Aamir Ali Khan PhD Biochemistry Principal Ghazali Institute of Medical Sciences Peshawar

2. Introduction Nucleotides are organic compounds made up of a PO 4 group, nitrogenous base & a sugar molecule. These are the building blocks of nucleic acids (DNA and RNA). They serve as sources of chemical energy (ATP, GTP), participate in cellular signalling (cAMP,  cGMP ) and function as important cofactors of enzymatic reactions (CoA, FAD, FMN, NAD + ).

3. SUGARS Two main sugars Present in furanose form Lacks 2’-OH group

4. Bases Purines : Adenine (A) Guanine (G) Pyrimidines : Cytosine (C) Uracil (U) Thymine (T) The bases are abbreviated by their first letters ( A, G, C, T , U ). The purines ( A, G ) occur in both RNA & DNA. Among the pyrimidines , C occurs in both RNA & DNA, but T occurs in DNA, and U occurs in RNA. DNA: A,G,C,T RNA: A,G,C,U

5. Nucleosides =Ribose/ Deoxyribose + Bases The bases are covalently attached to the 1’ position of a pentose sugar ring , to form a nucleoside

6. Nucleotides = nucleoside + phosphate A nucleotide is a nucleoside with one or more phosphate groups bound covalently to the 3 rd or 5 th hydroxyl group of pentose sugar. Most of nucleoside phosphate involve in biological function are 5’- phosphates. Since 5’- phosphates are most often seen, they are written without any prefix.

7. H H Ribonucleotide Deoxy-ribonucleotide Nucleoside

8. NOMENCLATURE Nucleosides phosphorylated on the 3’ or 5’ C of ribose are termed ; nucleoside 3’- monophoshate & nucleoside 5’- monophoshate. ‘5’ is by convention omitted when naming nucleotide. Abbreviations such as AMP, GTP denotes the phosphate is esterified to 5’ of pentose. Additional phosphate group is attached to preexisting phosphate of mononucleotide , - Nucleotide diphosphate – ADP - Nucleotide triphosphate – ATP

9. Nucleotide nomenclature:

10. Nucleotide nomenclature:

11. Individual properties PROPERTIES OF PURINE BASES:- Sparingly soluble in water Absorb light in UV region at 260 nm. (detection & quantization of nucleotides) Capable of forming hydrogen bond

12. Properties of pyrimidine bases Soluble at body pH Also absorb UV light at 260 nm Capable of forming hydrogen bond

13. Pyrimidine base :- Aromatic base atoms are numbered 1 to 6 for pyrimidine Atoms or group attached to base atoms have same number as the ring atom to which they are bonded

14. Cytosine :- Chemically is 2-oxy ,4-amino pyrimidine Exist both lactam or lactim form

15. Thymine :- Chemically is 2,4 dioxy ,5-methyl pyrimidine Occurs only in DNA

16. URACIL :- Chemically is 2,4 dioxy Pyrimidine Found only in RNA

17. PURINE BASES Aromatic base atoms numbered 1 to 9 Purine ring is formed by fusion of Pyrimidine ring with Imidazole ring Numbering is anticlockwise

18. ADENINE Chemically it is 6-aminopurine

19. Guanine :- Chemically is 2-amino,6-oxy purine Can be present as lactam & lactim form

20. CLASSIFICATION: Adenosine nucleotides ATP, ADP, AMP, Cyclic AMP Guanosine nucleotides GTP, GDP, GMP, Cyclic GMP Uridine nucleotides UTP, UDP, UMP, UDP-G Cytosine nucleotides CTP, CDP, CMP and certain deoxy CDP derivatives of glucose, choline and ethanolamine Miscellaneous PAPS (active sulphate ), SAM (active methionine ), certain coenzymes like NAD+, FAD, FMN, Cobamide coenzyme, CoA

21. ADENOSINE CONTAINING NUCLEOTIDES

22. ATP (ADENOSINE TRIPHOSPHATE) Many synthetic reactions requires energy, e.g. arginosuccinate synthetase reaction in urea cycle. ATP is required for the synthesis of Phospho creatine from creatine, synthesis of FA from acetyl CoA, formation of glucose from pyruvic acid, etc. ATP is an important source of energy for muscle contraction, transmission of nerve impulses, transport of nutrients across cell membrane, motility of spermatozoa. ATP is required for the formation of active Methionine , which is required for methylation reaction ATP donates phosphate for a variety of phosphotransferase reactions e.g., hexokinase reaction.

23. ADENOSINE DI PHOSPHATE (ADP) ADP plays an important role as a primary PO4 acceptor in oxidative phosphorylation and muscle contraction, etc ADP is also important as an activator of the enzyme glutamate dehydrogenase

24. ADENOSINE MONO PHOSPHATE (AMP) In the glycolytic pathway, the enzyme phosphofructokinase is inhibited by ATP but the inhibition is reversed by AMP. AMP can also act as an inhibitor of certain enzymes like fructose-1-6- bisphosphatase and adenylosuccinate synthetase. In resting muscles, AMP is formed from ADP, by adenylate kinase, the AMP produced activates the phosphorylase b enzyme of muscle and increase breakdown of glycogen.

25. AMP ROLE IN REGULATION

26. Miscellaneous :- PAPS - Phospho Adenosine Phospho Sulphate (active sulphate ) formed in liver Sulfates enzymes which catalyze introduction of SO4 group In biosynthesis of chondroitin sulfate Formation of sulpholipids SAM: - S- Adenosyl Methionine Active methionine

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