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Week%208-31 - The flow of genetic information Outline •...

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Unformatted text preview: The flow of genetic information Outline • the central dogma • the genetic code • mutations Reading assignments: Molecular Biology of the Gene (Watson, 6th ed) chapter 2, page 28-41 chapter 15, page 525-538. Three Models for the Replication of DNA DNA Replication Is Semi-Conservative (Messelson and Stahl, 1958) HH mix HL HH + HL DNA replication is semi-conservative Genes (DNA) control amino acid sequence in proteins (Vernon Ingram, 1957) DNA is not the direct template of protein synthesis DNA ? protein RNA is a different kind of nucleic acid DNA: deoxyribonucleic acid RNA: ribonucleic acid RNA contains Uracil G A T C G A U C RNA is synthesized upon DNA template by RNA polymerases coding strand template strand Major types of RNA molecules • messenger RNA (mRNA): gene-specific, contains future protein sequence information. • transfer RNA (tRNA): transfer specific amino acid to the site of protein synthesis. • ribosomal RNA (rRNA): structural component of ribosomes. • small non-coding RNA: regulatory functions. mRNA is the template of protein synthesis tRNAs bring the amino acids. The Central Dogma RNA can be used as template to synthesis DNA DNA transcription RNA translation protein replication reverse transcription Determining the genetic code 4 nucleotide ~ 20 amino acid 1 nucleotide/amino acid = 4 amino acids 2 nucleotides/amino acid = 16 amino acids 3 nucleotides/amino acid = 64 amino acids synthetic RNA template UUUUUUUUUUUU peptide PhePhePhePhe the genetic code • codon degeneracy • start codon • stop codon tRNA contains anticodon attaches amino acid tRNAs read the codons in mRNA • Translation happens in a 5’ to 3’ progression. • Codons are nonoverlapping. • The reading frame is fixed. Mutations alter the gene coding sequence Replacement of a nucleotide: • silent mutation • missense mutation • nonsense mutation Insertion or deletion: • frameshift mutation • deletion mutation The effect of mutations can be reversed by suppressor mutations • reverse mutation • intragenic suppressor • intergenic suppressor Free energy and biochemical reactions Outline • concept of free energy • chemical reactions involve changes in free energy • ATP is the main source of energy in cells Reading assignments: Molecular Biology of the Gene (Watson, 6th ed) chapter 3 p45-46, chapter 4 Most chemical reactions are bidirectional A+B AB equilibrium constant Keq = [AB]/[A] [B] • At equilibrium, the forward and reverse reactions occur at equal rates. Making and breaking chemical bonds involves changes in the form of energy • free energy (G) is the amount of energy available to do “work” (e.g.: thermal energy). • Energy can interconvert between forms such as thermal energy (kinetic) and bond energy (potential). • A decrease in free energy ( G<0) always occurs in spontaneous reaction --- 2nd law of thermodynamics. G can be used to determine the direction of a chemical reaction For chemical reaction: A + B AB G = Gproducts - Greactants If G < 0, reaction proceeds toward products If G = 0, reaction is at equilibrium If G > 0, reaction proceeds toward reactants G is related to Keq: G = -RT ln Keq Activation energy is required for the initiation of a reaction Enzymes lower activation energy Coupling of negative with positive G in a multi-step reaction ATP is the main cellular energy source Roles of ATP in Cells • Hydrolysis of the phosphoanhydride bonds of ATP (particularly as pyrophosphate) provides much of the free energy needed for many enzymatic reactions. • the major phosphate and adenylate donor in the cell. • a building block in RNA and is the precursor of dATP. • a major allosteric regulator of many proteins. May involve binding of ATP only, or binding and hydrolysis of ATP. Hydrolysis of high-energy phosphate bonds drives nucleic acid synthesis Biochemical bonds and interaction Outline • covalent bonds • non-covalent bonds • weak bonds mediate macromolecule interactions Reading assignments: Molecular Biology of the Gene (Watson, 6th ed) chapter 3 Covalent Bonds • Strong bonds, short, hold atoms close together. • Involves the sharing of an electron pair (or multiple pairs) between two atoms. • The valence of an atom determines the number of covalent bonds it can form. H-H, O=O, NN Valence is determined by the outer electron shell of atoms • Atoms bond in ways to minimize unpaired electrons. 5 Single covalent bonds allow rotation of atoms around the bond • Double and triple bonds do not allow for freedom of rotation. The numbers and types of bonds determine the geometry of molecules • Bond angles are determined by the number of atoms bonded together and seek to minimize the proximity of different atoms’ electrons to each other. Covalent bond can have electrical polarity Polar: Non-polar: • Differences in electronegativity between two atoms bonded together results in an electrical dipole or polar bond, which is the unequal sharing of electrons in a covalent bond. • When two atoms forming a bond do not differ much in electronegativity, the bond is non-polar. Non-covalent bonds • Ionic bonds: form by electrostatic attraction between charged groups (ions) and are the strongest of the noncovalent interactions. • Hydrogen bonds: form between an electronegative atom (e.g. nitrogen or oxygen) and a hydrogen atom that is covalently attached to another atom. • Hydrophobic “interactions”: occur between hydrophobic molecules because they are repelled by water. • Van der Waals attractions: occur between all molecules as a result of permanent and transient dipoles (unequal distribution of electrons). This is a very weak force. Ionic bonds can dissociate in solution NaCl Na+ + C l- Ionization State (Charge) of the carboxyl group can depend on pH • Acidic and basic groups may be protonated or deprotonated depending on the pH of the solution, which is a measure of the concentration of free H+. • At its pKa, the concentration of the two forms will be equal and there will be no net charge. Structures of Hydrogen Bonds • Remember: there is one hydrogen atom in a hydrogen bond. Examples of Hydrogen Bonds in Biological Molecules Water Forms a Hydrogen Bonding Lattice Van der Waals Forces Act between All Molecules • A non-specific attractive force. • Based on random and induced charge fluctuations give rise to transient dipoles (difference in charge). Hydrophobic Interactions Occur between Non-Polar Molecules Multiple Weak Bonds Combine to Produce Stable Associations between Macromolecules Complementary molecular surfaces ensure specific interactions antibody-antigen interaction the lock and key model ...
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