BBT 302: Molecules Of Life Lecture Notes PDF

BBT 302: Molecules of Life Mrs. Mary David, Asst. Professor, SBB, DYPU Unit IV Nucleic acids and Vitamins Lecture 15 Forms of DNA - A, B, and Z DNA, DNA and RNA properties,  Functions of Nucleotides Nucle...

BBT 302: Molecules of Life Mrs. Mary David, Asst. Professor, SBB, DYPU Unit IV Nucleic acids and Vitamins Lecture 15 Forms of DNA - A, B, and Z DNA, DNA and RNA properties,  Functions of Nucleotides Nucleic acid biosynthesis Energy production and transduction Protein biosynthesis Biosynthesis of some biomolecules. Regulatory cascades and cellular signal transduction Many coenzymes are nucleotide derivatives Synthetic nucleotide analogs are used in chemotherapy 4 Nucleosides nucleotides and Nucleic acids  Functions of Nucleotides Energy production and transduction Nucleoside triphosphates have high energy stored because of acid anhydride bonds. Cleavage of an acid anhydride bond is coupled with a highly endergonic reaction such as protein synthesis or nucleic acid synthesis which requires energy. Although ATP s the cell’s energy currency and donor of phosphoryl groups, all other nucleoside triphosphates (GTP, UTP, CTP) and all the deoxynucleoside triphosphates (dATP, dGTP, dTTP and dCTP) are energetically equivalent to ATP The free energy changes associated with hydrolysis of their phosphoanhydride linkages are very nearly identical with those for ATP 19 Nucleosides nucleotides and Nucleic acids  Functions of Nucleotides –Protein biosynthesis Initiation Elongation http://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-22/22_08.jpg 6 Nucleosides nucleotides and Nucleic acids https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcSPze2vCGnCiC5cIfjE6m_FU-pLHJ24jA76WslkC15MK5pRK87U  Functions of Nucleotides – Biosynthesis of biomolecules. UDP-sugar derivatives participate in sugar epimerization UDP-glucose is the glucosyl donor for biosynthesis of glycogen and glucosyldisaccharides Other UDP-sugars act as sugar donors for biosynthesis of oligosaccharides of glycoproteins and proteoglycans CTP is required for the biosynthesis of some phosphoglycerides CTP is required for the biosynthesis of sphingomyelin and other substituted sphingosines 7 Nucleosides nucleotides and Nucleic acids  Functions of Nucleotides – Regulatory Cascades Regulatory cascades or signaling cascades cAMP and cGMP are second messengers in signal transduction As a second messenger, cAMP participates in numerous regulatory functions by activating cAMP dependent protein kinases cAMP is synthesized by Adenylyl cyclase activity (regulated by complex interactions, many of which involve hormone receptors) and broken down by cAMP phosphodiesterase http://www.bioxys.com/i_asssaydesign/image/50_diagram_1.gif 8 Nucleosides nucleotides and Nucleic acids http://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-14/14_06.jpg  Functions of Nucleotides - many coenzymes are derivatives of nucleotides http://www.mikeblaber.org/oldwine/BCH4053/Lecture33/vitb2_01.jpg https://amit1b.files.wordpress.com/2013/11/figure-6.png http://i0.wp.com/jeffreydachmd.com/wp- 9 Nucleosides nucleotides and Nucleic acids content/uploads/2013/06/pantothenic_acid_chemical_structure.gif  Functions of Nucleotides : Synthetic nucleotide analogues are used in chemotherapy Chemically synthesized analogs of purines and pyrimidines, their nucleosides and their nucleotides find numerious applications in clinical medicine Administration of an analog in which either the heterocyclic ring or the sugar moiety has been altered induces toxic effect when the analog is incorporated into specific cellular constituents 10  Synthetic nucleotide analogues are used in chemotherapy Their effects reflect one of two processes: a)Inhibition by the drug of specific enzymes essential for nucleic acid synthesis b)Incorporation of metabolites of the drug into nucleic acids, thus they effect the base pairing required for accurate replication 11 Nucleosides nucleotides and Nucleic acids  Synthetic nucleotide analogues are used in chemotherapy 5-fluoro uracil → thymine analog https://patentimages.storage.googleapis.com/WO1 996013512A2/imgf000004_0001.png -iodo deoxyuridine → thyminide analog https://upload.wikimedia.org/wikipedia/commons/thumb/4/45/Idoxuridine_-_Idoxuridin.svg/2000px-Idoxuridine_-_Idoxuridin.svg.png 6-mercaptopurine → purine analaog http://oregonstate.edu/dept/biochem/hhmi/hhmiclasses/bb450/winter2002/MN/MERCPUR.GIF 6-thioguanine → purine analaog - http://www.sigmaaldrich.com/content/dam/sigma-aldrich/structure7/029/mfcd00233553.eps/_jcr_content/renditions/mfcd00233553-medium.png 12 Nucleosides nucleotides and Nucleic acids  Synthetic nucleotide analogues are used in chemotherapy 8-azaguanine → purine analaog 5 or 6-azauridine → pirimidine analaog 6-azacytidine → pirimidine analaog 13 Nucleosides nucleotides and Nucleic acids  Synthetic nucleotide analogues are used in chemotherapy (allopurinol) → purine analaog Allopurinol inhibits de novo purine biosynthesis and xanthine oxidase activity. It is used for treatment of hyperuricemia and gout https://upload.wikimedia.org/wikipedia/commons/5/56/Allopurinol_structure.png 14 Nucleosides nucleotides and Nucleic acids  Synthetic nucleotide analogues are used in chemotherapy The nucleoside, cytarabine (arabinosyl cytosine), in which arabinose replaces ribose, is used in chemotherapy and in treatment of viral infections Azathioprine is catabolized to 6-mercaptopurine and is used during organ transplantation to suppress immunological rejection 15 Nucleosides nucleotides and Nucleic acids Lecture 1 Biomolecules - Polynucleotides and Nucleic acid structure  Polynucleotides Mononucleotides are covalently linked through phosphate-group ‘bridges’ Specifically, the 3’-OH group of one nucleotide unit is joined to the 5’ - PO4-3 group of the next nucleotide by a phosphodiester linkage resulting in the release of one molecule water This results in a dinucleotide The term oligonucleotide is used for polymers containing 50 or fewer nucleotides 17 Polynucleotides http://media-2.web.britannica.com/eb-media/19/6519-004-88E853C5.jpg  Polynucleotides Polynucleotides are directional macromolecules Since the phosphodiester bond links 3’- and 5’- carbons of adjacent monomers, each end of a polymers is distinct. They are reffered as ‘3’-end’ or ‘5’-end’ of polynucleotides In the most representations displaying only the base sequences 5’ end is shown on the left and 3’ end is shown on the right: 5’ GTATTGC 3’ 18 Polynucleotides  Nucleic acid structure and function Genetic information is encoded in the DNA. The information in the DNA is transcribed into the different types of RNA which are involved in protein synthesis. The nucleic acids, DNA and RNA are made up of nucleotide monomeric units dNTPs and NTPs respectively linked together by phosphodiester bonds. The phosphodiester bonds can be hydrolyzed by phosphodiesterases. 19 Polynucleotides  The double helical model Watson & Crick determined that a DNA molecule is a double helix – two strands twisted around each other Their model was based on base composition studies conducted by Erwin Chargaff and X-ray diffraction studies conducted by Maurice Wilkins and Rosalind Franklin http://image.slidesharecdn.com/16lecturedna-150106204625-conversion- 20 Polynucleotides gate01/95/ch-16-the-molecular-basis-of-inheritance-25-638.jpg?cb=1420577525  Discovering DNA’s Structure Chargaff’s 1949 observations – Chargaff extracted DNA of different organisms and carried out chromatographic studies on them. He found the following observations: The amount of adenine always equaled the amount of thymine; amount of guanine always equaled the amount of cytosine;Thus the purine : pyrimidine ratio = 1 or A+G = T + C or A+G / T +C = 1 * - Purines * - Pyrimidines However A+ T / G + C = n Where n varied between different species of organisms, but remained the same in all orgs of the same species and in all tissues of the same organism and does not change with age, nutritional status or changing environment of the organism. 21 Polynucleotides  Wilkins & Franklin’s Photographs X-ray diffraction to study the structures of molecules 1952 Maurice Wilkins & Rosalind Franklin developed high-quality X-ray diffraction photographs of strands of 22 DNA which suggested that the DNA resembled a tightly coiled helix and was composed of two or three chains of nucleotides 22 Polynucleotides  Rosalind Franklin Rosalind Franklin was an English scientist who contributed to the discovery of the molecular structure of deoxyribonucleic acid (DNA), 1951 23 Polynucleotides  Watson & Crick’s DNA Model In 1953 Watson & Crick used the information from Chargaff, Wilkins, & Franklin along with their knowledge of chemical bonding, to make the “spiral staircase” configuration of DNA 24 Polynucleotides http://userscontent2.emaze.com/images/add81bfa-828e-42f2-aa07-6138d9fdc410/d028f6c0-a706-40de-a6d0-2b257cb58d7a.jpg  Watson & Crick’s DNA In DNA there are two strands of nucleotides that are wound Model around each other in a right handed helix. The strands have opposite polarity or are anti-parallel. i.e when one strand is in 5’ to 3’ direction, the other is in 3’ to 5’ direction The bases are arranged towards the interior of the double helix. The sugar phosphate backbone is in the exterior. The two strands are held together by means of hydrogen bonds between the nitrogen bases. Each nitrogen base is specifically bonded to its complement. Thus an A is always bonded to a T by means of a double hydrogen bonds while a G is always bonded to a C by means of a triple bond. Since a purine is always bonded to a pyrimidine the two strands are equidistant from each other throughout the length of the DNA. The DNA has a diameter of 2 nm (20 Ao). The 0.34 nm and 3.4 nm periodicities observed in the X-ray diffraction pattern can be explained as the distance between two adjacent base pairs and the distance two turns of DNA respectively. Thus each turn of the DNA has 10 base pairs. The DNA shows the presence of a minor groove (the space between the two strands) and a major groove (the space between two adjoining turns of DNA) 25 Polynucleotides http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/104944953/73_1_2.jpg  Base Pairing in the DNA Double Helix 26 Polynucleotides http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/104573282/74---Copy_1_2.jpg Thank You