Bài giảng Biochemistry 2/e - Chapter 11: Nucleotides and Nucleic Acids

Chapter 11Nucleotides and Nucleic Acidsto accompanyBiochemistry, 2/ebyReginald Garrett and Charles GrishamAll rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline11.1 Nitrogenous Bases 11.2 The Pentoses of Nucleotides and NA 11.3 Nucleosides are Formed by Joining a Nitrogenous Base to a Sugar 11.4 Nucleotides - Nucleoside Phosphates 11.5 Nucleic Acids are Polynucleotides 11.6 Classes of Nucleic Acids 11.7 Hydrolysis of Nucleic Acids Information Transfer in CellsSee Figure 11.1 Information encoded in a DNA molecule is transcribed via synthesis of an RNA molecule The sequence of the RNA molecule is "read" and is translated into the sequence of amino acids in a protein. 11.1 Nitrogenous BasesKnow the basic structures Pyrimidines Cytosine (DNA, RNA) Uracil (RNA) Thymine (DNA) Purines Adenine (DNA, RNA) Guanine (DNA, RNA) Properties of Pyrimidines and PurinesKeto-enol tautomerism Acid/base dissociations Strong absorbance of UV light11.2 Pentoses of NucleotidesKnow these structures too D-ribose (in RNA) 2-deoxy-D-ribose (in DNA) The difference - 2'-OH vs 2'-H This difference affects secondary structure and stability 11.3 NucleosidesLinkage of a base to a sugar Base is linked via a glycosidic bond The carbon of the glycosidic bond is anomeric Named by adding -idine to the root name of a pyrimidine or -osine to the root name of a purine Conformation can be syn or anti Sugars make nucleosides more water-soluble than free bases11.4 NucleotidesNucleoside phosphates Know the nomenclature "Nucleotide phosphate" is redundant! Most nucleotides are ribonucleotides Nucleotides are polyprotic acids Functions of NucleotidesNucleoside 5'-triphosphates are carriers of energy Bases serve as recognition units Cyclic nucleotides are signal molecules and regulators of cellular metabolism and reproduction ATP is central to energy metabolism GTP drives protein synthesis CTP drives lipid synthesis UTP drives carbohydrate metabolism11.5 Nucleic Acids - PolynucleotidesPolymers linked 3' to 5' by phosphodiester bridges Ribonucleic acid and deoxyribonucleic acid Know the shorthand notations Sequence is always read 5' to 3' In terms of genetic information, this corresponds to "N to C" in proteins 11.6 Classes of Nucleic AcidsDNA - one type, one purpose RNA - 3 (or 4) types, 3 (or 4) purposes ribosomal RNA - the basis of structure and function of ribosomes messenger RNA - carries the message transfer RNA - carries the amino acids The DNA Double HelixStabilized by hydrogen bonds! "Base pairs" arise from hydrogen bonds Erwin Chargaff had the pairing data, but didn't understand its implications Rosalind Franklin's X-ray fiber diffraction data was crucial Francis Crick knew it was a helix James Watson figured out the H-bonds The Structure of DNAAn antiparallel double helix Diameter of 2 nm Length of 1.6 million nm (E. coli) Compact and folded (E. coli cell is only 2000 nm long) Eukaryotic DNA wrapped around histone proteins to form nucleosomes Base pairs: A-T, G-C Messenger RNATranscription product of DNA In prokaryotes, a single mRNA contains the information for synthesis of many proteins In eukaryotes, a single mRNA codes for just one protein, but structure is composed of introns and exons Eukaryotic mRNADNA is transcribed to produce heterogeneous nuclear RNA mixed introns and exons with poly A intron - intervening sequence exon - coding sequence poly A tail - stability? Splicing produces final mRNA without introns Ribosomal RNARibosomes are about 2/3 RNA, 1/3 protein rRNA serves as a scaffold for ribosomal proteins 23S rRNA in E. coli is the peptidyl transferase! Transfer RNASmall polynucleotide chains - 73 to 94 residues each Several bases usually methylated Each a.a. has at least one unique tRNA which carries the a.a. to the ribosome 3'-terminal sequence is always CCA-a.a. Aminoacyl tRNA molecules are the substrates of protein synthesisDNA & RNA Differences?Why does DNA contain thymine? Cytosine spontaneously deaminates to form uracil Repair enzymes recognize these "mutations" and replace these Us with Cs But how would the repair enzymes distinguish natural U from mutant U? Nature solves this dilemma by using thymine (5-methyl-U) in place of uracil DNA & RNA Differences?Why is DNA 2'-deoxy and RNA is not? Vicinal -OH groups (2' and 3') in RNA make it more susceptible to hydrolysis DNA, lacking 2'-OH is more stable This makes sense - the genetic material must be more stable RNA is designed to be used and then broken down Hydrolysis of Nucleic AcidsRNA is resistant to dilute acid DNA is depurinated by dilute acid DNA is not susceptible to base RNA is hydrolyzed by dilute base See Figure 11.29 for mechanism Restriction EnzymesBacteria have learned to "restrict" the possibility of attack from foreign DNA by means of "restriction enzymes" Type II and III restriction enzymes cleave DNA chains at selected sites Enzymes may recognize 4, 6 or more bases in selecting sites for cleavage An enzyme that recognizes a 6-base sequence is a "six-cutter"Type II Restriction EnzymesNo ATP requirement Recognition sites in dsDNA usually have a 2-fold axis of symmetry Cleavage can leave staggered or "sticky" ends or can produce "blunt” endsType II Restriction EnzymesNames use 3-letter italicized code: 1st letter - genus; 2nd,3rd - species Following letter denotes strain EcoRI is the first restriction enzyme found in the R strain of E. coli