200L MBBS, NUCLEOSIDES ETC-1.pptx

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1. NUCLEOTIDES, NUCLEOSIDE AND NUCLEIC ACIDS

2. NUCLEOSIDE A nucleoside is composed of purine and pyrimidine base and sugar. Nucleosides are classified based on the nitrogneous base present as purine nucleosides or pyrimidine nucleosides In the case of purine nucleosides, the sugar is attached to N-9 of purine ring where as in pyrimidine nucleosides the sugar is attached to N-1 of pyrimidine ring. The type of linkage is N- glycosidic and sugar can be ribose or deoxyribose .

3. PURINE NUCLEOSIDE They contain purine bases adenine and guanine. Adenosine is nucleoside of adenine and guanosine is the nucleoside of guanine. If adenine is linked to deoxyribose then it is named as deoxy adenosine Adenosine = Adenine+Ribose Guanosine = Guanine+Ribose

4. UNUSUAL NUCLEOSIDES Ribothymidine and pseudouridine are examples of unusual nucleosides. Ribothymidine consist of thymine and ribose. It is present in ribonucleic acids (RNA) which is not usually found. Pseudouridine is an unusual nucleoside of uracil . In this nucleoside carbon–carbon bonding occurs between uracil and ribose instead of the carbon –nitrogen bond.

5. Pyrimidine nucleosides These nucleosides are composed of pyrimidine bases. Cytosine, Uracil and thymine are pyrimidine nitrogenous bases. Cytidine is nucleoside of cytosine . Uridine and thymidine are nucleosides of uracil and thymine respectively. Cytidine = Cytosine + Ribose Uridine = Uracil + Ribose Thymidine = Thymine+ Ribose

6. NUCLEOTIDES They are phosphorylated nucleosides. A nucleotide consist of nitrogenous base, sugar and phosphate. Nucleotide = Purine or Pyrimidine base + Sugar + Phosphate

7. IMPORTANT BIOLOGICAL FUNCTIONS OF NUCLEOTIDES AND NUCLEOSIDES. 1. Nucleotides are involved in signal transduction. 2. Nucleotides are required for the formation of nucleic acids. 3. Nucleotides are high energy compounds. 4. Nucleotides are components of some water soluble vitamin coenzymes. 5. Nucleotides serve as second messengers. Many hormones mediate their action through second messengers. 6. Some nucleotides function as donors of sugars, nitrogenous compounds and phosphates. 7. Nucleosides function as carriers or donors of groups. 8. Nucleoside analogs are used as anti cancer agents. 9. Some nucleotides function as alarmones . They alarm cell when something goes wrong in the cell.

8. Synthetic analogs of purines , pyrimidines and nucleosides Some synthetic purine and pyrimidine analogs are used as anticancer agents and antiviral gents. Purine analogs are mercaptopurine , thioguanine , aminopurine etc. Pyrimidine analog is 5- fluro uracil . Nucleoside analogs are used as anticancer agents, antiviral agents and mutagens. Deazauridine , 6-aza uridine , ara -A, ara -C and fluro deoxyuridine are nucleoside analogs used as anticancer agents. Azidothymidine (AZT), dideoxy cytidine and iododeoxyuridine are used as anti viral agents. Bromodeoxy uridine is used as mutagen.

9. Pharmacologically important purines Caffeine of coffee, theophylline of tea and theobromine of tea are some purines of pharmacological importance. Caffeine and theophylline act as CNS stimulants. Inhalers used by asthma patients contains theophylline . It releives nasal and bronchial congestion of these patients.

10. Nucleotides of biochemical ( Physiological) importance Cells present in various organs of human body and other mammals contain several free nucleotides. These free nucleotides are involved in many biochemical or biological processess

11. Adenine nucleotides and their physiological importance 1. Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) are most important adenine nucleotides. 2. ATP, ADP, and AMP are high energy compounds. 3. ATP is popularly called as 'energy currency' of cell. Energy exchange in biochemical reactions occurs through ATP. 4. ADP is required for the formation of ATP in electron transport chain and in energy yielding reactions. 5. cAMP , a cyclic nucleotide of adenine is known as second messenger. Many hormones action occurs through cAMP . 6. Many coenzymes of water soluble vitamins contain adenine nucleotides. For example NAD, FAD, NADP, coenzyme A and cobamide coenzymes.

12. 7. PAPS ( Phospho adenosine phosphosulfate ) serve as donor of sulfate in biosynthetic reactions. 8. ATP is required for replication and protein biosynthesis. 9. Some adenosine nucleotides are involved in blood pressure and platelet function. 10 Diadenosine nucleotides are neurotransmitters. 11. Oligoadenylate mediates action of interferon. 12. Poly adenylate serve as tail of mRNA

13. Guanine nucleotides and their physiological importance 1. Like ATP, ADP; Guanosine triphosphate (GTP) and guanosine diphosphate (GDP) also exist in cells. 2. GTP and GDP are high energy compounds. 3. Cyclic GMP or cGMP mediates actions of several hormones. 4. GTP and GDP are components of G-proteins which are involved in signal transduction of several physiological processes like taste, odor, vision, metabolic regulation etc. 5. GTP is required for replication and protein biosynthesis. 6. Guanine nucleotides are required for catalytic function of ribonucleic acids or ribozymes . 7. Mucopolysacharide formation requires guanine nucleotides.

14. Cytosine nucleotides of physiological importance 1. CTP ( Cytidine triphosphate ), CDP ( Cytidine diphosphate ) and CMP( Cytidine monophsphate ), are high energy compounds. 2. Cyclic CMP or cCMP also occurs in cells. 3. CDP, CMP serve as donor of nitrogenous compounds during biosynthesis. 4. CMP-NANA serve as donor of NANA in the biosynthesis of gangliosides . 5. CDP- choline serve as donor of choline in phospholipids biosynthesis.

15. Uracil nucleotides of physiological importance 1. UTP( Uridine triphosphate ), UDP ( Uridine diphosphate ) and UMP ( Uridine monophosphate ) are high energy compounds. 2. UDP- Glucuronic acid serve as donor of glucuronic acid in the synthesis of mucopolysacharides , bilirubin diglucuronide and detoxification reactions. 3. UDP is carner of sugar and aminosugars needed for synthesis of glycogen, gangliosides , glycoproteins etc.

16. Thymine nucleotides of physiological importance TTP( thymidine triphosphate ), TDP( thymidine diphosphate ) and TMP( thymidine monophosphate ) are high energy compounds. 2. TTP and d TTP are used for the synthesis of nucleic acids.

17. Hypoxanthine and xanthine These are purine bases not found in nucleic acids. But their nucleotides have important role in metabolism. 1. IDP ( inosine diphosphate ), IMP ( inosine monophosphate ) are nucleotides of hypoxanthine. They are high energy compounds. 2. IMP is intermediate in purine nucleotide biosynthesis. 3. XMP ( xanthosine monophosphate ) is an intermediate in purine nucleotide biosynthesis.

18. NUCLEIC ACIDS Two types of nucleic acids are found in cells. They are deoxy ribonucleic acid (DNA) and ribonucleic acid (RNA). Pentose sugar in DNA is deoxyribose where as in RNA it is ribose. Due to deoxyribose nucleotides present in DNA are known as deoxy ribonucleotides . They are designated as dADP , dATP ; dGDP , dGTP , dTTP , dTDP , dCTP , dCDP etc. Both DNA and RNA are polymers of nucleotides and often referred as polynucleotides .

19. DNA structure 1. It consist of two polynucleotide chains. 2. These polynucleotide chains coil along long axis in the form double helix. 3. Each polynucleotide is made up of four types of nucleotides. 4. Individual nucleotides are joined by phosphodiester bonds. 5. Four types of nucleotides are present in two chains. They are adenylicacid , guanylic acid, cytidylic acid and thymidylic acid. 6. Each polynucleotide chain or strand has direction or polarity and 5‘ and 3'ends. 7. These ends may be in either free form or phosphorylated form.

20. 8. The two strands are complementary to each other. 9. Base composition of a strand is complementary to opposite strand. If thymine is found in one strand adenine appears in opposite strand and vice versa. Like wise if guanine appears in one strand cytosine is found in opposite strand and vice versa. 10. Further bases of opposite strands are involved in pairing. It is popularly known as base pairing rule. Adenine of one strand pairs with thymine of opposite strand through two hydrogen bonds. Guanine of a strand pairs with cytosine of opposite strand through three hydrogen bonds.

21. DNA double helix one helical turn 34 Å major groove 12 Å minor groove 6 Å backbone : deoxyribose and phosphodiester linkage bases

22. 11. Due to the presence of three hydrogen bonds GC pair is stronger than AT pair. 12. This base pairing makes copying mechanism simple and easier. 13. Complementary nature of two strands and base pairing rule are most outstanding features of Watson-Crick model. 14. The base pairs are stacked. The pitch of the helix is 34 A and contain ten base pairs. The width of the helix is 20 A . 15. Due to the presence of hydrogen bonds throughout the molecule DNA is highly stable. 16. Major and minor grooves are present on the double helix. 17. Watson- Crick model DNA is known as B-DNA.

23. Functions DNA 1. DNA is genetic material of living organisms. It contains all the information needed for the development of entire organism or individual. 2. DNA is transferred from parent to the offspring or generation to generation. 3. DNA contains information required for formation of individuals proteins. 4. Information is present in DNA in the form of genes. 5. Amount of DNA present in the cell of an organism depends on complexity of organisms. 6. Human cells contain more DNA than bacterial cells or viruses. 7. DNA amount in given cell is independent of nutritional or metabolic state of the organism. 8. DNA flows from generation to generation in any given species. 9. DNA determines physical fitness of an organism or susceptibility to disease.

24. RNA There are three types of RNAs in cells. They are present in prokaryotes as well as eukaryotes. They are (1). Messenger RNA or mRNA (2). Transfer RNA or tRNA (3). Ribosomal RNA or rRNA .

25. MESSENGER RNA 1. Majority of mRNA molecules are linear polymers. 2. They contain about 1000-10, 000 nucleotides. 3. They have 3' or 5' free or phosphorylated ends 4. Life span of m RNA molecules varies from few minutes to days. 5. Some RNAs have secondary structure. 6. Intra strand base pairing among complementary bases leads to folding of linear molecules into hair pin like secondary structure. 7. In some m RNA at 5'and 3' ends special nucleotides or sequences occurs. 8. Poly A tail is present in some mRNAs at 3' end. 9. At 5' end some mRNA are capped. Methylated GTP is cap. 10. At 5' and an AG rich shine – Dalgarno sequence is present in some mRNAs

26. Functions 1. mRNA carries genetic information from nucleus to cytoplasm. 2. Generally one mRNA contains information for formation one protein. 3. The sequence of mRNA is complementary to strand from which it is copied. 4. In mRNA genetic information is present in the form of genetic code. 5. Occasionally one mRNA contains information for the formation of more than one protein.

27. Transfer RNA ( tRNA ) It is smallest of all RNAs and contains up to 100 nucleotides. It contains several unusual bases like pseudouridine , dihydro uracil , mythylated adenine and guanine and isopentenyl adenine etc. Due to intra strand base pairing between complementary bases tRNA molecules exist in characteristic secondary structure shape. Secondary structure of tRNAs is in the form of clover leaf.

28. Structural features of tRNA 1. It contains an aminoacid arm at 3' end CCA is characteristic sequence of aminoacid arm. 2. An arm containing unusual pseudouridine and ribothymidine . Hence it is known as T φ C arm in which pseudouridine is indicated with psi ( φ ) symbol. 3. An anticodon arm containing IGC sequence. Generally this arm recognizes codon on mRNA. 4. Dihydrouridine (UH ) arm or DHU arm that contains dihydrouracil . 5. A guanine containing 5'end.

29. Functions 1. It serve as adaptor molecule in protein biosynthesis. It carries amino acids to site of protein synthesis. 2. For every aminoacid one specific tRNA molecule exist. 3. Stability of eukaryotic and prokaryotic tRNA varies.

30. Ribosomal RNA ( rRNA ) It is found in combination with proteins in ribosomes . It contains about 100-600 nucleotides. Prokaryotic and eukaryotic ribosomes contain several RNA that differ in sedimentation coefficient. Due to intra strand base pairing between complementary bases secondary structures are found in rRNA molecules. They are known as domains. 16S rRNA with 1500 nucleotides has four major domains.

31. Functions 1. It is involved in initiation of protein synthesis. 2. It is required for the formation of ribosomes .

32. Differences between DNA and RNA DNA Double stranded molecule Found in combination with proteins. Pentose sugar is deoxyribose. Sum of the purine bases is equal to sum of pyrimidine bases. A+G=C+T Pyrimidine base uracil is absent. Only one form of DNA predominantly occurs. Resistant to alkaline hydrolysis. Modified bases are usually absent. Lacks catalytic activity. RNA 1. Single stranded molecule. 2. Except rRNA other RNAs exist as free molecules 3. Pentose sugar is ribose. 4. Sum of purine bases is not equal to sum of pyrimidine bases. 5. Thymine a pyrimidine base is not usually found. 6. More than three types of RNAs occurs. 7. Easily hydrolyzed by alkali. 8. Unusual and modified bases are found. 9. Some RNAs act as enzymes or posses catalytic activity