1. Pyrimidines and Purines Nucleic Acids Nucleosides Nucleotides

2. Base Nucleoside Nucleotide (base + ribose) (nucleoside + phosphate) (base + ribose) (nucleoside + phosphate) Adenine Adenosine AMP (adenylic acid or adenosine monophosphate) or adenosine monophosphate) Guanine Guanosine GMP (guanylic acid or guanosine monophosphate) or guanosine monophosphate) Uracil Uridine UMP (uridylic acid or uridine monophosphate) or uridine monophosphate) Thymine Thymidine TMP (thymidylic acid or thymidine monosphosphate) or thymidine monosphosphate) Cytosine Cytidine CMP (cytidylic acid or cytidine monophosphate) or cytidine monophosphate)

5. Pyrimidines and Purines In order to understand the structure and properties of DNA and RNA, we need to look at their structural components. We begin with certain heterocyclic aromatic compounds called pyrimidines and purines.

6. The Nitrogenous Bases In DNA: AdenineGuanine*Thymine*Cytosine In RNA: AdenineGuanine *Uracil* *Uracil*Cytosine

7. Pyrimidines and Purines Pyrimidine and purine are the names of the parent compounds of two types of nitrogen- containing heterocyclic aromatic compounds. N N N N N NH PyrimidinePurine

8. Important Pyrimidines Pyrimidines that occur in DNA are cytosine and thymine. Cytosine and uracil are the pyrimidines in RNA. HNHNHNHN NHNHNHNHOO Uracil HNHNHNHN NHNHNHNHOO CH 3 Thymine HNHNHNHN NHNHNHNH NH2NH2NH2NH2 O Cytosine

9. Important Purines Adenine and guanine are the principal purines of both DNA and RNA. Adenine N N NH2NH2NH2NH2N NHNHNHNH GuanineO HNHNHNHN NHNHNHNH N N H2NH2NH2NH2N

10. Nitrogenous Bases Planar, aromatic, and heterocyclicPlanar, aromatic, and heterocyclic Numbering of bases is “unprimed”Numbering of bases is “unprimed”

11. Nucleosides

12. Nucleosides Result from linking one of the sugars with a purine or pyrimidine base through an N- glycosidic linkage The classical structural definition is that a nucleoside is a pyrimidine or purine N-glycoside of D -ribofuranose or 2-deoxy- D -ribofuranose. Informal use has extended this definition to apply to purine or pyrimidine N-glycosides of almost any carbohydrate. The purine or pyrimidine part of a nucleoside is referred to as a purine or pyrimidine base.

13. Sugars Pentoses (5-C sugars)Pentoses (5-C sugars) Numbering of sugars is “primed”Numbering of sugars is “primed”

14. Sugars D-Ribose and 2’-Deoxyribose D-Ribose and 2’-Deoxyribose *Lacks a 2’-OH group

15. NH2NH2NH2NH2HOOH O HOCH 2 O N N Pyrimidine nucleosides Cytidine occurs in RNA; its 2-deoxy analog occurs in DNA CytidineCytidine

16. ON NHNHNHNH O HO O H3CH3CH3CH3C HOCH 2 Pyrimidine nucleosides Thymidine occurs in DNA ThymidineThymidine

17. Uridine and Adenosine Uridine and adenosine are pyrimidine and purine nucleosides respectively of D -ribofuranose. Uridine (a pyrimidine nucleoside) Adenosine (a purine nucleoside) ON HOCH 2 HNHNHNHN O OHHO O N N N N O OHHO NH2NH2NH2NH2

18. Nucleotides

19. Nucleotides Result from linking one or more phosphates with a nucleoside onto the 5’ end of the molecule through esterificationResult from linking one or more phosphates with a nucleoside onto the 5’ end of the molecule through esterification

20. Nucleotides Chemical compound composed of three components: (1) heterocyclic base; (2) sugar (usually a pentose); and (3) one or more phosphate groups Adenosine monophosphate (AMP) Base Pentose sugar Phosphate Glycosidic bond

21. Nucleotides Nucleotides are phosphoric acid esters of nucleosides.  Nucleotides are building blocks of nucleic acids.  They are non-essential nutrients, because they can be synthesized in the body. synthesized in the body.  Nucleic acids occur in the nucleoprotein.

22.  Dietary nucleoprotein is digested in the stomach to yield protein and nucleic acids. protein and nucleic acids.  Nucleic acids are further digested in the small intestine to generate nucleotides. generate nucleotides.  Nucleotides are absorbed into intestinal mucosa cells, where they are degraded to three components : base, where they are degraded to three components : base, pentose and phosphate. pentose and phosphate.  Pentose is absorbed but base is degraded and excreted.

23. Function of neucleotides Precursors for RNA and DNA synthesisPrecursors for RNA and DNA synthesis ATP plays an important pole in energy transformation.ATP plays an important pole in energy transformation. Physiological Mediators (cAMP)Physiological Mediators (cAMP) Components of coenzymes (NAD + )Components of coenzymes (NAD + )Components of coenzymes (NAD + )Components of coenzymes (NAD + ) Allosteric effectors and donor of phosphate group (phosphorylation)Allosteric effectors and donor of phosphate group (phosphorylation) Formation of activated intermediatesFormation of activated intermediates UDP-glucose, CDP-choline UDP-glucose, CDP-choline

24. Energy Currency

25. Carriers for Activated Intermediates

26. Structural Components of: Coenzyme A Flavin adenine dinucleotide (FAD) NAD(P) +

27. Signaling Molecules

28. Naming Conventions Nucleosides:Nucleosides: –Purine nucleosides end in “-sine” Adenosine, GuanosineAdenosine, Guanosine –Pyrimidine nucleosides end in “-dine” Thymidine, Cytidine, UridineThymidine, Cytidine, Uridine Nucleotides:Nucleotides: –Start with the nucleoside name from above and add “mono-”, “di-”, or “triphosphate” Adenosine Monophosphate, Cytidine Triphosphate, Deoxythymidine DiphosphateAdenosine Monophosphate, Cytidine Triphosphate, Deoxythymidine Diphosphate

29. Adenosine 5'-Monophosphate (AMP) Adenosine 5'-monophosphate (AMP) is also called 5'- adenylic acid. N N N N O OHHO NH2NH2NH2NH2 OCH 2 P HO O HO 1' 2'3' 4' 5'

30. Adenosine Diphosphate (ADP) N N N N O OHHO NH2NH2NH2NH2 OCH 2 P O O HO P O HO HO

31. Adenosine Triphosphate (ATP) N N N N O OHHO NH2NH2NH2NH2 OCH 2 P O O HO P O HO O P O HO HO

32. ATP Stores Energy AMP ADP ATP Each step is endothermic. Energy for each step comes from carbohydrate metabolism (glycolysis). Reverse process is exothermic and is the source of biological energy.  G° for hydrolysis of ATP to ADP is –35 kJ/mol

33. cAMP and cGMP Cyclic AMP and cyclic GMP are "second messengers" in many biological processes. Hormones (the "first messengers") stimulate the formation of cAMP and cGMP. Cyclic adenosine monophosphate (cAMP) CH 2 O OH N N N NH 2 N O O P O HO

34. Adenosine 3'-5'-Cyclic Monophosphate (cAMP) Cyclic AMP is an important regulator of many biological processes. N N N N O OHO NH2NH2NH2NH2 CH 2 P O HO O

35. cAMP and cGMP Cyclic AMP and cyclic GMP are "second messengers" in many biological processes. Hormones (the "first messengers") stimulate the formation of cAMP and cGMP. O O P O HO Cyclic guanosine monophosphate (cGMP) CH 2 N NH OON NH 2 N OH

36. Nucleic Acids

37. Nucleic acids are polymeric nucleotides (polynucleotides). 5' Oxygen of one nucleotide is linked to the 3' oxygen of another.

38. Chemical Structure of a Nucleic Acid Voet Fig. 3-6

39. Note that the strands run antiparallel Note that the helix is 20 Å wide. There are about 10 base pairs per turn of the helix. One turn of the helix is 34 Å The base pairs are 3.4 Å apart Double Helical Structure of DNA Major groove

40. RNA (ribonucleic acid) is a polymer of ribonucleotidesRNA (ribonucleic acid) is a polymer of ribonucleotides DNA (deoxyribonucleic acid) is a polymer of deoxyribonucleotidesDNA (deoxyribonucleic acid) is a polymer of deoxyribonucleotides

41. Nucleic Acids 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. Scientists revised their opinion of the function of DNA and began to suspect it was the major functional component of genes.

42. Composition of DNA Erwin Chargaff (Columbia Univ.) studied DNAs from various sources and analyzed the distribution of purines and pyrimidines in them. The distribution of the bases adenine (A), guanine (G), thymine (T), and cytosine (C) varied among species. But the total purines (A and G) and the total pyrimidines (T and C) were always equal. Moreover: %A = %T, and %G = %C

43. Composition of Human DNA Adenine (A) 30.3%Thymine (T) 30.3% Guanine (G) 19.5%Cytosine (C) 19.9% Total purines: 49.8%Total pyrimidines: 50.1% For example: PurinePyrimidine

44. Structure of DNA James D. Watson and Francis H. C. Crick proposed a structure for DNA in 1953. Watson and Crick's structure was based on: Chargaff's observations X-ray crystallographic data of Maurice Wilkins and Rosalind Franklin Model building

45. Base Pairing Watson and Crick proposed that A and T were equal because of complementary hydrogen bonding. 2-deoxyribose 2-deoxyribose AT

46. Base Pairing Likewise, the amounts of G and C were equal because of complementary hydrogen bonding. 2-deoxyribose 2-deoxyribose GC

47. The DNA Duplex Watson and Crick proposed a double-stranded structure for DNA in which a purine or pyrimidine base in one chain is hydrogen bonded to its complement in the other. Gives proper Chargaff ratios (A=T and G=C) Because each pair contains one purine and one pyrimidine, the A---T and G---C distances between strands are approximately equal. Complementarity between strands suggests a mechanism for copying genetic information.

48. Fig. 27.24 Two antiparallel strands of DNA are paired by hydrogen bonds between purine and pyrimidine bases.

49. Fig. 27.25 Helical structure of DNA. The purine and pyrimidine bases are on the inside, sugars and phosphates on the outside.

50. Tertiary Structure of DNA: Supercoils

51. DNA is coiled A strand of DNA is too long (about 3 cm in length) to fit inside a cell unless it is coiled. Random coiling would reduce accessibility to critical regions. Efficient coiling of DNA is accomplished with the aid of proteins called histones.

52. Histones Histones are proteins rich in basic amino acids such as lysine and arginine. Histones are positively charged at biological pH. DNA is negatively charged. DNA winds around histone proteins to form nucleosomes.

53. Histones Each nucleosome contains one and three-quarters turns of coil = 146 base pairs. Linker contains about 50 base pairs.

54. Histones Nucleosome= Histone proteins + Supercoiled DNA

55. Fig. 27.26 DNA Replication C G T A As the double helix unwinds, each strand acts as a template upon which its complement is constructed.

56. Fig. 27.26 DNA Replication A C G T T' A' G' C'

57. Fig. 28.8 DNA Replication The DNA to be copied is a double helix, shown here as flat for clarity. The two strands begin to unwind. (next slide)

58. Fig. 28.8 DNA Replication Each strand will become a template for construction of its complement.

59. Fig. 28.8 DNA Replication Two new strands form as nucleotides that are complementary to those of the original strands are joined by phosphodiester linkages. Polynucleotide chains grow in the 5'-3' direction—continuous in the leading strand, discontinuous in the lagging strand.

60. Fig. 28.8 DNA Replication Two duplex DNAs result, each of which is identical to the original DNA.

61. Elongation of the growing DNA chain The free 3'-OH group of the growing DNA chain reacts with the 5'-triphosphate of the appropriate nucleotide.

62. Fig. 28.9 Chain elongation OH CH 2 O OP O O– OP O O– OP O O– O–O–O–O– Adenine,Guanine, Cytosine, or Thymine OH CH 2 OPO O Adenine,Guanine, Cytosine, or Thymine O O– Poly- nucleotide chain

63. Fig. 28.9 Chain elongation OH CH 2 O OP O–O–O–O– Adenine,Guanine, Cytosine, or Thymine O CH 2 OPO O Adenine,Guanine, Cytosine, or Thymine O O– Poly- nucleotide chain O OPOO– OPOO– O–O–O–O– –

64. Ribonucleic Acids

65. DNA and Protein Biosynthesis According to Crick, the "central dogma" of molecular biology is: "DNA makes RNA makes protein." Three kinds of RNA are involved. messenger RNA (mRNA) transfer RNA (tRNA) ribosomal RNA (rRNA) There are two main stages. transcription translation

66. Transcription In transcription, a strand of DNA acts as a template upon which a complementary RNA is biosynthesized. This complementary RNA is messenger RNA (mRNA). Mechanism of transcription resembles mechanism of DNA replication. Transcription begins at the 5' end of DNA and is catalyzed by the enzyme RNA polymerase.

67. Fig. 28.10 Transcription Only a section of about 10 base pairs in the DNA is unwound at a time. Nucleotides complementary to the DNA are added to form mRNA.

68. The Genetic Code The nucleotide sequence of mRNA codes for the different amino acids found in proteins. There are three nucleotides per codon. There are 64 possible combinations of A, U, G, and C. The genetic code is redundant. Some proteins are coded for by more than one codon.

69. UUUPheUCUSer UAUTyrUGUCysU UUCPheUCCSerUACTyrUGCCysC UUALeuUCASerUAAStopUGAStopA UUGLeuUCGSerUAGStopUCGTrpG UCAGUCAGUCAGUCAGU C A G First letter Second letter Third letter Table 28.3 (p 1175)

70. UUUPheUCUSer UAUTyrUGUCysU UUCPheUCCSerUACTyrUGCCysC UUALeuUCASerUAAStopUGAStopA UUGLeuUCGSerUAGStopUCGTrpG CUULeuCCUPro CAUHisCGUArgU CUCLeuCCCProCACHisCGCArgC CUALeuCCAProCAAGlnCGAArg A CUGLeuCCGProCAGGlnCCGArg G AUUIleACUThr AAUAsnAGUSer U AUCIleACCThrAACAsnAGCSer C AUAIleACAThrAAALysAGAArg A AUGMetACGThrAAGLysACGArg G GUUValGCUAla GAUAspGGUGly U GUCValGCCAlaGACAspGGCGly C GUAValGCAAlaGAAGluGGAGly A GUGValGCGAlaGAGGluGCGGly G UCAGU C A G

71. 28- 71 UC UAAStopUGAStopA UAGStopG UC A G AUUIleACUThr AAUAsnAGUSer U AUCIleACCThrAACAsnAGCSer C AUAIleACAThrAAALysAGAArg A AUGMetACGThrAAGLysACGArg G U C A GUCAGU C A G AUG is the "start" codon. Biosynthesis of all proteins begins with methionine as the first amino acid. This methionine is eventually removed after protein synthesis is complete. UAA, UGA, and UAG are "stop" codons that signal the end of the polypeptide chain.

72. Transfer tRNA There are 20 different tRNAs, one for each amino acid. Each tRNA is single stranded with a CCA triplet at its 3' end. A particular amino acid is attached to the tRNA by an ester linkage involving the carboxyl group of the amino acid and the 3' oxygen of the tRNA.

73. Transfer RNA Example—Phenylalanine transfer RNA One of the mRNA codons for phenylalanine is: UUC5'3' AAG 3'5' The complementary sequence in tRNA is called the anticodon.

74. Fig. 28.11 Phenylalanine tRNA OCCHCH 2 C 6 H 5 + NH 3 O Anticodon 3' 5' 3' 5'

75. Ribosomal RNA Most of the RNA in a cell is ribosomal RNA Ribosomes are the site of protein synthesis. They are where translation of the mRNA sequence to an amino acid sequence occurs. Ribosomes are about two-thirds RNA and one- third protein. It is believed that the ribosomal RNA acts as a catalyst—a ribozyme.