2. Nucleosides,Nucleotides & Nucleic acids

3. (i) DNA- Genomic information (nucleosomes, chromatin) This chemical substance is present in the nucleus of all cells in all living organisms It controls all the chemical changes which take place in cells The kind of cell which is formed, (muscle, blood, nerve etc) is controlled by DNA The kind of organism which is produced (giraffe, human etc) is controlled by DNA It is composed of deoxyribonucleotides (Double stranded). 90% in nuclei and the rest in mitochondria store and carry genetic information (forms chromosomes, units of genetic information which pass from parent to offspring) determine the genotype of cells (ii) RNA - Messenger RNA, Ribosomal RNA and Transfer RNA It is composed of ribonucleotides (Single stranded). It is present in nuclei and cytoplasm It participate in the gene expression Information encoded in a DNA molecule is transcribed via synthesis of an RNA molecule (iii) PNA - Peptide nucleic acids mimic nucleic acids

4. Base(purine, pyrimdine)+ Sugar (ribose, deoxyribose) N-glycosyl linkage Nucleoside+phosphate phosphoester linkage Nucleotide phosphodiester linkage Nucleic acid

5. Nucleic Acids (Informational Polymers) Nucleic acids first isolated in 1869 (Johann Miescher) Oswald Avery discovered (1945) that a substance which caused a change in the genetically transmitted characteristics of a bacterium was DNA. Nucleic acids are molecules that store information for cellular growth and reproduction These are the chemical link between generations dating back to the beginning of life on earth. It is a complex macromolecule that stores information in cells in the form of a genetic code. It is biopolymer composed of long chains of monomers called nucleotides linked in a linear sequential order through 3’,5’-phosphodiester bonds A nucleotide consists of a nitrogenous base, a pentose sugar and a phosphate group

6. Nitrogen Bases

7. The nitrogen bases in nucleotides consist of two general types: - purines: adenine (A) and guanine (G) - pyrimidines: cytosine (C), thymine (T) and Uracil (U)

8. Caffeine (coffee), theobromine (coca) and theophylline (tea) are naturally occurring purines. Caffeine / 1,3,7-Trimethylxanthine N NON N H3CH3CH3CH3C O CH 3 Theobromine / 3,7-Dimethylxanthine O HNHNHNHN N N N CH 3 O Theophylline / 1,3-dimethylxanthine

10. Naturally Occurring Pyrimidines

11. Pentose Sugars There are two related pentose sugars: - RNA contains ribose - DNA contains deoxyribose The sugars have their carbon atoms numbered with primes to distinguish them from the nitrogen bases

12. Nucleosides and Nucleotides A nucleoside consists of a nitrogen base linked by a glycosidic bond to C1’ of a ribose or deoxyribose Nucleosides are named by changing the nitrogen base ending to -osine for purines and –idine for pyrimidines A nucleotide is a nucleoside that forms a phosphate ester with the C5’ OH group of ribose or deoxyribose Nucleotides are named using the name of the nucleoside followed by 5’- monophosphate Building blocks for DNA and RNA Intracellular source of energy - Adenosine triphosphate (ATP) Second messengers - Involved in intracellular signaling (e.g. cyclic adenosine monophosphate [cAMP]) Intracellular signaling switches (e.g. G-proteins)

13. Names of Nucleosides and Nucleotides

14. Some minor purine and pyrimidine bases, shown as the nucleosides Minor bases of DNAMinor bases of tRNAs

15. Some adenosine monophosphates

17. Ribonucleotides of nucleic acids

18. Deoxyribonucleotides of nucleic acids

19. The  -P atom of the triphosphate group of a dNTP (deoxy ribonucleotide triphosphate) attacks the C-3’ OH group of a nucleotide or an existing DNA chain, and forms a 3’-phosphoester bond. Phosphoester bond formation

20. Phosphodiester bonds Alternative phosphodiester bonds and pentoses constitute the 5’-3’ backbone of nucleic acids.

21. Phosphodiester bonds link successive nucleotides in nucleic acids Some adenosine monophosphates Phosphodiester linkages in the covalent backbone of DNA and RNA

23. Nucleic acid Nitrogenous BaseSugar DNA A、G、C、TA、G、C、T deoxyribose RNA A、G、C、UA、G、C、U ribose Composition of DNA and RNA

24. Nucleic Acid Derivatives - AMP, d-AMP, ADP and ATP (Multiple Phosphate Nucleotide) Additional phosphate groups can be added to the nucleoside 5’- monophosphates to form diphosphates and triphosphates ATP is the major energy source for cellular activity

25. Cyclic ribonucleotide: 3’,5’-cAMP, 3’,5’- cGMP, used in signal transduction cAMP Nucleic acid derivatives CH 2 N NH OON NH 2 N OH cGMP

26. Nucleic Acid Derivatives (dAMP) (CMP) (UMP) (TMP)

27. Biologically active systems containing ribonucleotide: NAD +, NADP +, CoA-SH Nucleic acid derivatives

28. Primary Structure of Nucleic Acids The primary structure of a nucleic acid is the nucleotide sequence The nucleotides in nucleic acids are joined by phosphodiester bonds The 3’-OH group of the sugar in one nucleotide forms an ester bond to the phosphate group on the 5’-carbon of the sugar of the next nucleotide

29. Reading Primary Structure A nucleic acid polymer has a free 5’-phosphate group at one end and a free 3’-OH group at the other end The sequence is read from the free 5’-end using the letters of the bases This example reads 5’—A—C—G—T—3’

30. Example of RNA Primary Structure In RNA, A, C, G, and U are linked by 3’-5’ ester bonds between ribose and phosphate

31. Example of DNA Primary Structure In DNA, A, C, G, and T are linked by 3’-5’ ester bonds between deoxyribose and phosphate

32. Secondary Structure: DNA Double Helix In DNA there are two strands of nucleotides that wind together in a double helix - the strands run in opposite directions - the bases are arranged in step-like pairs - the base pairs are held together by hydrogen bonding The pairing of the bases from the two strands is very specific The complimentary base pairs are A-T and G-C - two hydrogen bonds form between A and T - three hydrogen bonds form between G and C Each pair consists of a purine and pyrimidine. So they are the same width, keeping the two strands at equal distances from each other.

33. Base Pairing in the DNA Double Helix

35. Complementarity of strands in the DNA double helix

36. The bases always pair up in the same way Adenine forms a bond with Thymine and Cytosine bonds with Guanine Bonding 1 AdenineThymine Cytosine Guanine

37. PO 4 thymine PO 4 adenine cytosine PO 4 guanine Bonding 2

38. PO 4 Pairing up

40. Hydrogen Bonding Maintains the Double Helix Stability

41. Storage of DNA In eukaryotic cells (animals, plants, fungi) DNA is stored in the nucleus, which is separated from the rest of the cell by a semipermeable membrane. The DNA is only organized into chromosomes during cell replication. Between replications, the DNA is stored in a compact ball called chromatin, and is wrapped around proteins called histones to form nucleosomes.

42. Ribonucleic Acid (RNA) RNA is much more abundant than DNA There are several important differences between RNA and DNA: - the pentose sugar in RNA is ribose, in DNA it’s deoxyribose - in RNA, uracil replaces the base thymine (U pairs with A) - RNA is single stranded while DNA is double stranded - RNA molecules are much smaller than DNA molecules There are three main types of RNA: - ribosomal (rRNA), messenger (mRNA) and transfer (tRNA)

43. Types of RNA

44. Ribosomal RNA and Messenger RNA Ribosomes are the sites of protein synthesis - they consist of ribosomal DNA (65%) and proteins (35%) - they have two subunits, a large one and a small one Messenger RNA carries the genetic code to the ribosomes - they are strands of RNA that are complementary to the DNA of the gene for the protein to be synthesized

45. Transfer RNA Transfer RNA translates the genetic code from the messenger RNA and brings specific amino acids to the ribosome for protein synthesis Each amino acid is recognized by one or more specific tRNA tRNA has a tertiary structure that is L-shaped - one end attaches to the amino acid and the other binds to the mRNA by a 3-base complimentary sequence

46. Protein Synthesis The two main processes involved in protein synthesis are - the formation of mRNA from DNA (transcription) - the conversion by tRNA to protein at the ribosome (translation) Transcription takes place in the nucleus, while translation takes place in the cytoplasm Genetic information is transcribed to form mRNA much the same way it is replicated during cell division

47. Hydrolysis of RNA under alkaline conditions

48. Synthetic Nucleotide analogs used in Medicine