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The biochemistry of nucleic acids

The biochemistry of nucleic acids

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The biochemistry of nucleic acids

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  1. The biochemistry of nucleic acids Tommer Ravid Room 1-523 Tel: 658 4349 e-mail: travid@cc.huji.ac.il

  2. Metabolism of nucleic acids (DNA and RNA) 1. In many cases requires proofreading. 2. In many cases requires a plan (template) in addition to substrates. 3. Unusual definition of substrate. 4. Different substrates at different times, at different cells. 5. Unusual structural organization. Unusual problems for enzymes and regulators to act on the nucleic acid. 6. Utilizing nucleotides as building blocks.

  3. A generic scheme of a nucleotide. Three chemical components connected with covalent bonds: 1. A nitrogenous base. 2. A pentose mostly a ribose in its ring form. 3. A phosphate (one or more). Nucleoside: a pentose and a base with no phosphate group

  4. Deoxyribonucleotides

  5. Building Block for RNA and DNA Not a building block for DNA

  6. The name of the nucleotide is determined by the base (simply because it is the variable component in the molecule) Numbers of carbon atoms on the ribose are marked with ‘ to distinguish from the atom numbers of the nitrogenous base. Bases come from two families, purines and pyrimidines.

  7. How many purines and how many pyrimidines do we know?

  8. Some less known (but not rare at all) nitrogenous bases Specific for bacteria (involved in repair) Specific to mammals and higher plants. Found in bacteria infected by phages.

  9. Some more of the less known bases (found in tRNAs)

  10. Nucleotide sequence of yeast tRNAAla I: Inosine : Pseudouridine T: Ribothimidine D: 5,6-dihydrouridine M1l: 1-methylinosine M1G: 1-methylguanosine M2G: dimethylguanosine

  11. General secondary structure of tRNAs

  12. To remember by heart: Formulas of: ATP, GTP, CTP, UTP dATP,dGTP,dCTP,dTTP

  13. Some cellular functions of nucleotides Building blocks of nucleic acids. 2. Energy carrier (ATP, GTP). 3. Building parts of enzymes co-factors (e.g., NAD, FAD, CoenzymeA, S-adenosylmethionine). 4. Regulators in signal transduction processes. 5. Second messengers in signal transduction (cAMP, cGMP). 6. Phosphate donors in phosphorylation reactions. 7. Serve as structural molecules (rRNA). 8. Activators of carbohydrates for synthesis (glycogen for example).

  14. Adenosine 5’-triphosphate (ATP) High concentrations in cells - a problem of balance in nucleotides concentration.

  15. Coenzyme A Thioester Modified ADP High free energy of hydrolysis High acyl group transfer potential (to many acceptor molecules) Vitamin required (pantothenate)

  16. Some cellular functions of nucleotides Building blocks of nucleic acids. 2. Energy carrier (ATP, GTP). 3. Building parts of enzymes co-factors (e.g., NAD, FAD, CoenzymeA, S-adenosylmethionine). 4. Regulators in signal transduction processes. 5. Second messengers in signal transduction (cAMP, cGMP). 6. Phosphate donors in phosphorylation reactions. Involved in many more pottranslational modifications. 7. Serve as structural molecules (rRNA). 8. Activators of carbohydrates for synthesis (glycogen for example).

  17. Some cellular functions of deoxynucleotides Building blocks of nucleic acids (DNA). 2. Energy carrier (ATP, GTP). 3. Building parts of enzymes co-factors (e.g., NAD, FAD, CoenzymeA, S-adenosylmethionine). 4. Regulators in signal transduction processes (GTP). 5. Second messengers in signal transduction (cAMP, cGMP). 6. Phosphate donors in phosphorylation reactions. 7. Serve as structural molecules (rRNA). 8. Activators of carbohydrates for synthesis (glycogen for example).

  18. Chemical properties of nucleotides 1. Components of nucleotides are independently reacting with other molecules. Hydroxyls are nucleophils. Phosphate nuclei are electrophiles. The components of a given nucleotide rarely react with each other. 2. All components are covalently linked - the bonds are saturated and can rotate freely. The ribose can also acquire several conformations. 3. Nitrogen bases are planar (allowing close contacts that eliminate water molecules for example). 4. Ribose and phosphate groups are hydrophylic while bases are hydrophobic. 5. Electronegative atoms in the bases rings. These atoms are capable of forming hydrogen bonds. 6. The bases are ‘conjugated molecules’ in which the atoms are closed and the orbitals are delocalized over the entire ring. As a result the bases are planar. They also absorb UV light (pick at about 260nm). 7. The glycosidic bond is always in a b configuration.

  19. Conformations of ribose

  20. Where the cells obtain nucleotides from ?

  21. De novo synthesis provides nucleotides in the mono-phosphate form. Specific kinases provide nucleotides di-phosphate and tri-phosphate.

  22. Deoxyribonucleotides

  23. Reduction of ribonucleotides to deoxyribonucleotides by ribonucleotide reductase

  24. Ribonucleotide reductase

  25. The basic reaction in nucleotide polymerization. Catalyzed by all known polymerases.

  26. The driving force towards synthesis is the breakdown of Pyrophosphate (PPi). Pyrophosphatase PPi+H2O 2Pi Phosphodiester bond

  27. Hydrolysis of RNA under alkaline conditions

  28. DNA/RNA structure