5 nucleotides and nucleic acids lecture

1. Principle of Biochemistry 5-Nucleotides and Nucleic Acids Course code: HFB324 Credit hours: 3 hours Dr Siham Gritly Dr Siham Gritly 1

2. Nucleoside, Nucleotide & Nucleic acid Dr Siham Gritly 2 nucleoside nucleotides nucleic acids

3. DNA, RNA and the nucleobases Dr Siham Gritly 3

4. Deoxyribonucleotide ; monomeric building block of DNA; a phosphate group and a nitrogenous base both bonded to deoxyribose Ribonucleotide ; monomeric building block of RNA; a phosphate group and a nitrogenous base both bonded to ribose sugar Duplex; two complementary strands of DNA Mutant; genetically altered species or cell Dr Siham Gritly 4

5. Nucleoside; nitrogenous base bonded to ribose or deoxyribose Nucleotide; monomeric building block of RNA and DNA; a phosphate group and a nitrogenous base both bonded to ribose or deoxyribose Nucleic Acids are Polynucleotides Phosphodiester ; two different alcohols forming ester linkages with one phosphate ion Dr Siham Gritly 5

6. Replication; DNA synthesis Template; a section of DNA which is being replicated or transcribed; mRNA which is being translated Transcription; synthesis of RNA from DNA Translation; synthesis of proteins from an RNA template Dr Siham Gritly 6

7. Nucleotides and Nucleic Acids Introduction; Nucleic acids are macromolecules present in all living cells in combination with protein with high concentration of basic amino acids to form nucleoproteins. ( protamines and histones ) Nucleic acids compounds carrying information -- the genetic molecules (DNA and RNA ) . Dr Siham Gritly 7

8. The nucleic acids are of two types -1-deoxyribonucleic acid DNA -2-ribonucleic acid RNA DNA is present in the nuclei small amounts present in the mitochondria RNA is present in the cell cytoplasm (90%) about 10% present in the nucleolus Dr Siham Gritly 8

9. Nucleotides Nucleoside phosphates Nucleotides are monomers of nucleic acids The nucleotides found in cells are derivatives of the heterocyclic highly basic, compounds, purine and pyrimidine present in DNA and RNA (nitrogenous bases) Heterocyclic are ring compounds that contain both carbon atom and non-carbon atoms --mainly nitrogen atom . Dr Siham Gritly 9

10. Nucleotide Structures of purine and pyrimidine Heterocyclic ring compounds Dr Siham Gritly 10 Nitrogenous Bases Single six-sided ring pyrimidinesC4H4N2 Double ring purines (six- and five-sided) C5H4N4

11. Types of nucleotide bases There are five major bases found in cells. The derivatives of purine are called adenine and guanine (found in both DNA & RNA) , the derivatives of pyrimidine are called thymine, cytosine and uracil . Dr Siham Gritly 11

12. The derivatives of purine ; adenine and guanine (found in both DNA & RNA) 1-Adenine 6-aminopurine, 2-Guanine 2-amino-6-oxypurine Dr Siham Gritly 12

13. the derivatives of pyrimidine are thymine, cytosine and uracil . Cytosine- 2-oxy-4-aminopyrimidine, Uracil-n2,4-dioxypyrimidineThymine-2,4-dioxy-, 5-methyl Dr Siham Gritly 13

14. The common abbreviations used for these five bases are, A, G, T, C and U. Cytosine & Uracil in RNA Cytosine and thymine in DNA The nucleotide uridine is never found in DNA thymine is almost exclusively found in DNA. Thymine is found in tRNAs but not rRNAs nor mRNAs Dr Siham Gritly 14

15. Nucleotides mainly; Pentose sugar+ β -N- glycosidic bond+ phosphoryl group Derivative of purines and pyrimidines are nucleotides- ---contain mainly cyclyized sugar Pentose linked to nitrogen hetroatom by β -N- glycosidic bond additional to phosphoryl group esterified to hydroxy group of the sugar ( β -D-ribose or β -D-2-deoxyribose) Dr Siham Gritly 15

16. Nucleotides mainly; 1-pentose sugar. 2-phosphate groups. 3-a nitrogeous base 1-5–carbon sugar component Ribose Deoxyribose Dr Siham Gritly 16

17. 5–carbon sugar component; Ribose and Deoxyribose Furanose structures Dr Siham Gritly 17

18. 2-Phosphate group Attached to the sugar's 5' carbon with a phosphodiester bond 3-Nitrogen Base component attached to the sugar's 1'carbon . Dr Siham Gritly 18

19. Functions of Nucleotides Components of nucleic acids (which are long chains of nucleotides) ATP ( Adonosine TriPhosphate ) is central to energy metabolism GTP ( Guanosine TriPhosphate ) drives protein synthesis CTP ( Cytidine Triphosphate ) drives lipid synthesis UTP ( Uridine Triphosphate ) drives carbohydrate metabolism Dr Siham Gritly 19

20. Energy transport coenzymes (NAD+, NADP+, FAD+) Chemical intracellular messengers (e.g., Cyclic AMP, a cyclic nucleotide that carries messages from the cell membrane to molecules within the cell, to stimulate essential reactions. regulators of cellular metabolism and reproduction ) Dr Siham Gritly 20

21. Nucleosides Nucleoside consist of purine and pyrimidine bases and a sugar β -D-ribose or β -D-2-deoxyribose linked through a covalent β -N- glycosidic bond Therefore Nucleosides are Formed by Joining a Nitrogenous Base to a Sugar Base is linked via a β -N- glycosidic bond Dr Siham Gritly 21

22. β -N- glycosidic bond linked nitrogen-9 of the purine base or nitrogen-1 of the pyrinidine base with carbon1 of pentose sugar Dr Siham Gritly 22

23. The nucleosides of A, G, C,T, U are named A denine ---Adenosine G uanine ---- Guanisine C ytosine ---- Cytidine T hymine ---- Thymidine U racil ----- Uridine Purine nucleosides end “ osine ” Pyrinidine ends in “ idine ” Ribose sugar produced; ribonucleoside 2-deoxyribose sugar produced; deoxyribonucleosides Dr Siham Gritly 23

24. The nucleosides in DNA are called ; deoxyadenosine , deoxyguanosine , deoxycytidine , and thymidine , the nucleosides in RNA are called ; adenosine, guanosine , cytidine , and uridine . If the base is a purine , then the N-9 (nitrogen) is bonded to the C-1' (carbon) of the sugar. If the base is a pyrimidine , then the N-1 is bonded to the C-1' of the sugar. Dr Siham Gritly 24

25. Common nucleosides Dr Siham Gritly 25

26. Glycosidic Bond Configurations Dr Siham Gritly 26

27. The base can exist in 2 distinct orientations about the N - glycosidic bond. These conformations are identified as, syn and anti . It is the anti conformation that predominates in naturally occurring nucleotides Dr Siham Gritly 27 Syn - adenosine anti-adenosine

28. Nucleotides and nucleosides that are not part of DNA or RNA the importance of free nucleotide Some nucleotides are not part of DNA or RNA but still play important roles in a cell. cyclic adenosine monophosphate ( cAMP ) is an intracellular signal: it communicates information from one part of the cell to another. Other nucleotides are coenzymes, which are molecules that help enzymes work properly (FAD, NAD). Dr Siham Gritly 28

29. Adenosine triphosphate (ATP) Dr Siham Gritly 29 Adenosine triphosphate (ATP) is a common and critical energy transfer molecule. The bonds that hold three phosphate groups to adenosine store energy. They form when energy is released and transfer that energy to other places in a cell.

30. Adenosine Monophosphates (AMP) Dr Siham Gritly 30

31. Nucleic acid polynucletide the nucleic acids are polymers of subunits of monomers nucleotides. Nucleic acid; important substance that all cellular organisms use to store their genetic information. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acids Dr Siham Gritly 31

32. The chemical linkage between nucleotide units in nucleic acids is a phosphodiester , which connects the 5’-hydroxyl group of one nucleotide to the 3’-hydroxyl group of the next nucleotide. Phosphodiester bonds are essential to all life, as they make up the backbone of each helical strand of DNA. In DNA and RNA, the phosphodiester bond is the linkage between the 3’ carbon atom of one sugar molecule and the 5’ catbon atom of another; the sugar molecules deoxyribose in DNA and ribose in RNA. Hydrolysis of phosphodiester bonds can be catalyzed by the action of phosphodiest erases Dr Siham Gritly 32

33. Sequences of RNA and DNA structures The chemical linkage between monomer units in nucleic acids is a phosphodiester Dr Siham Gritly 33

34. phosphodiester , connects the 5’-hydroxyl group of one nucleotide to the 3’-hydroxyl group of the next nucleotide. Dr Siham Gritly 34

35. Formation of phosphodiester bonds Formed by Polymerase and Ligase activities Dr Siham Gritly 35

36. classes of nucleic acids 1- Deoxyribonucleic acid DNA Deoxyribonucleic acid (DNA) is a nucleic acid containing the genetic instructions used in the development and functioning of all known living organisms (with the exception of RNA viruses). The DNA segments carrying this genetic information are called genes . Genes (specific regions of DNA molecules) contain the hereditary information of an organism. Dr Siham Gritly 36

37. When organisms reproduce The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription. Within cells DNA is organized into long structures called chromosomes , ( packaged form of the DNA). During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes (46). Within the chromosomes, chromatin proteins such as histones compact and organize DNA. Dr Siham Gritly 37

38. DNA structure and function DNA structure is the well-known double helix formed by Watson-Crick base-pairing of C with G and A with T. This is known as B-form DNA , and is the most favorable and common state of DNA; its highly specific and stable base-pairing is the basis of reliable genetic information storage. Dr Siham Gritly 38

39. Structure of DNA naturally occurring DNA molecules are double-stranded Dr Siham Gritly 39 Watson-Crick model for the structure of DNA

40. Tertiary Structure of DNA: Supercoils . Each cell contains about two meters of DNA. DNA is “packaged” by coiling around a core of proteins known as histones . The DNA- histone assembly is called a nucleosome . Histones are rich is lysine and arginine residues Dr Siham Gritly 40

41. the Watson-Crick model James Watson and Francis Crick proposed a model for the structure of DNA. This model predicted that DNA would exist as a helix of two complementary antiparallel strands, wound around each other in a rightward direction and stabilized by H-bonding between bases in adjacent strands . Dr Siham Gritly 41

42. They proposed that in any given molecule of DNA,;- the concentration of adenine (A) is equal to thymine (T) and the concentration of cytidine (C) is equal to guanine (G). This means that A will only base-pair with T, and C with G. According to this pattern, known as Watson-Crick base-pairing, the base-pairs composed of G and C contain three H-bonds, whereas those of A and T contain two H-bonds. This makes G-C base-pairs more stable than A-T base-pairs. Dr Siham Gritly 42

43. Base pairing model Dr Siham Gritly 43

44. Base pairs are stabilized by H-bonding Dr Siham Gritly 44

45. the base-pairs composed of G and C contain three H-bonds, whereas those of A and T contain two H-bonds . Dr Siham Gritly 45

46. Watson-Crick base-pairing of C with G and A with T Dr Siham Gritly 46

47. Complementarity of strands in the DNA double helix Dr Siham Gritly 47 -Adenine (A) and thymine (T) always pair together (A–T), -cytosine (C) and guanine (G) always pair together (C–G). In other words, A and T are complementary bases , as are C and G.

48. Replication of DNA as suggested by Watson and Crick Dr Siham Gritly 48 Replication: process by which DNA is copied itself

49. Two polynucleotide strands, running in opposite directions ( anti-parallel ) and coiled around each other in a double helix . The strands are held together by complementary hydrogen- bonding between specific pairs of bases Dr Siham Gritly 49

50. REPLICTION, TRANSCRIPTION AND TRANSLATION Dr Siham Gritly 50

51. Function of DNA 1-store of genetic information; genetic information is the source of information for the synthesis of all protein molecules. The information is copied or transcribed into RNA molecules Proteins are then synthesized in the process involving the translation of the RNA Dr Siham Gritly 51

52. 2-DNA provides the inherited information by the daughter cell. DNA provide template for the replication of information into daughter DNA molecule Dr Siham Gritly 52

53. 2- Ribonucleic acid RNA Ribonucleic acid RNA is a long unbranched macromolecules consisting of nucleotides joined by 3’ to 5’ phosphodiester bonds. It is the same as DNA but it possesses different characteristic RNA differ from DNA in that it is a single strand do not contain regions of double helical structure Dr Siham Gritly 53

54. RNA contain ribose sugar instead of 2-deoxyribose that present in DNA contain four major bases 1-purine bases;-Adenine and Guanine 2-pyrimidin bases;- Cytosine and Uracil RNA contain Uracil instead of thymine RNA pairs Adenine with Uracil and Cytosine with Guanine Dr Siham Gritly 54

55. Structure of RNA RNA molecules are single-stranded Dr Siham Gritly 55 RNA contain Uracil instead of thymine RNA pairs Adenine with Uracil and Cytosine with Guanine

56. Ribonucleic acid (RNA) functions Ribonucleic acid (RNA) functions in converting genetic information from genes into the amino acid sequences of proteins. RNA translates the DNA message to a format that can be read by ribosomes , or the cellular organelles that assemble proteins (process known as translation). RNA also plays a role in engage the correct amino acids to the protein meeting sites. Dr Siham Gritly 56

57. types of RNA The three universal types of RNA include 1-transfer RNA ( tRNA ), transfer RNA serves as the carrier molecule for amino acids to be used in protein synthesis, and is responsible for decoding the mRNA. 2-messenger RNA (mRNA ), messenger RNA acts to carry genetic sequence information between DNA and ribosomes , directing protein synthesis 3-ribosomal RNA ( rRNA ). ribosomal RNA is a major component of the ribosome, and catalyzes peptide bond formation. Dr Siham Gritly 57

58. RNA & DNA structures Dr Siham Gritly 58

59. PHOSPHODIESTER BOND LINK NUCLETIDES Dr Siham Gritly 59

60. references Murry K. Robert, Granner K. daryl , Mayes A. peter, Rodwell W. Victor (1999). Harpers Biochemistry. Appleton and Lange , twent fifth edition A. Burtis , Edward R. Ashwood , Norbert W. Tietz (2000), Tietz fundamentals of clinical chemistry Maton , Anthea ; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart , Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. pp. 52–59 Dr Siham Gritly 60

61. references Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York: W. H. Freeman and Company. Matthews, C. E.; K. E. Van Holde ; K. G. Ahern (1999) Biochemistry. 3rd edition. Benjamin Cummings. Naik Pankaja (2010). Biochemistry. 3ed edition, JAYPEE Maitland, Jr Jones (1998). Organic Chemistry. W W Norton & Co Inc ( Np ). p. 139. ISBN 0-393-97378-6 . Dr Siham Gritly 61

62. Pentose sugar Dr Siham Gritly 62

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