Nucleotides & Nucleic Acids Page 325 Chapter 10 Nucleotides & Nucleic Acids
Nucleic acids: linear polymers of nucleotides Page 325 Nucleic acids: linear polymers of nucleotides linked 3’ to 5’ by phosphodiester bridges (bond) ---DNA (deoxyribonucleic acid) ---RNA (ribonucleic acid)
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=nucleoside + phosphate =base + sugar
What Are the Structure and Chemistry of Nitrogenous Bases?
Page 325 Nitrogenous Bases
Pyrimidine Page 326 Purine
Three Pyrimidines Are Commonly Found in Cells Page 326 & 327 The common pyrimidine bases – cytosine, uracil, and thymine – in the tautomeric forms predominant at pH 7.
Two Purines Are Commonly Found in Cells Page 326 & 327 Figure 10.4 The common purine bases – adenine and guanine – in the tautomeric forms predominant at pH 7.
Page 327 Figure 10.5 Other naturally occurring purine derivatives – hypoxanthine, xanthine, and uric acid.
Tautomerization Page 327 The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their carbonyl and ring nitrogen substituents endow them with the capacity to undergo keto–enol tautomeric shifts.
Tautomerization Page 327
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Page 328 Another property of pyrimidines and purines is their strong absorbance of ultraviolet (UV) light, which is also a consequence of the aromaticity of their heterocyclic ring structures.
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The Properties of Pyrimidines and Purines Can Be Traced to Their Electron-Rich Nature Page 326 & 327 The aromaticity and electron-rich nature of pyrimidines and purines enable them to undergo keto-enol tautomerism The keto tautomers of uracil, thymine, and guanine predominate at pH 7 By contrast, the enol form of cytosine predominates at pH 7 Protonation states of the nitrogens determines whether they can serve as H-bond donors or acceptors Aromaticity also accounts for strong absorption of UV light
What Are Nucleosides?
Nucleoside=base +sugar Page 328 Nucleoside=base +sugar
The Common Monosaccharides Have Cyclic Structure Page 206 & 207 The Common Monosaccharides Have Cyclic Structure anomeric carbon 半縮醛 anomeric carbon 1
Page 207 & 208 anomeric carbon 半縮酮 2 anomeric carbon
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Page 329 Purine nucleosides and nucleotides usually adopt the anti conformation, where the purine ring is not above the ribose, as it would be in the syn conformation. Pyrimidines are always anti, never syn, because the 2-O atom of pyrimidines sterically hinders the ring from a position above the ribose.
Adenosine: A Nucleoside with Physiological Activity Page 328 Adenosine functions as an autacoid, or local hormone, and neuromodulator. Circulating in the bloodstream, it influences blood vessel dilation, smooth muscle contraction, neurotransmitter release, and fat metabolism. Adenosine is also a sleep regulator. Adenosine rises during wakefulness, promoting eventual sleepiness. Caffeine promotes wakefulness by blocking binding of adenosine to its neuronal receptors.
Summary-Nucleosides Page 329 The base is linked to the sugar 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 bases
Nomenclature命名法 Page 329
What Is the Structure and Chemistry of Nucleotides?
Nucleotide= base + sugar + phosphate Page 329 & 330
Cyclic Nucleotides Are Cyclic Phosphodiesters Page 330
cGAMP, a Cyclic Dinucleotide that Triggers a Response to Infection Page 331 Cyclic dinucleotides such as c-di-GMP have been known since 1987 and their occurrence is as second messengers. The presence of DNA in the cytosol of animal cells is an indication of an invading bacterium or virus In response, the cytosolic DNA sensor, cyclic GMP-AMP synthase, synthesizes cGAMP Rising [cGAMP] levels trigger expression of stimulator of interferon genes (STING) and an immune response An undesirable consequence of this system is that self-nucleic acid recognition (host DNA in the cytosol) may induce autoimmune diseases such as lupus erythematosus紅斑性狼瘡
c-di-GMP is a signal that causes bacteria to switch from free-living single cells into formation of biofilms Page 331
cGAMP, a Cyclic Dinucleotide that Triggers a Response to Infection Page 331
Page 330 & 331 Figure 10.13 Formation of ADP and ATP by the succesive addition of phosphate groups via phosphoric anhydride linkages. Shown here is ATP synthesis. Note that the reaction is a dehydration synthesis.
*NDPs and NTPs Are Polyprotic Acids Page 315 *NDPs and NTPs Are Polyprotic Acids *Nucleoside 5’-Triphosphate Are Carriers of Chemical Energy
Nucleoside 5'-Triphosphates Are Carriers of Chemical Energy Page 332 Nucleoside 5'-triphosphates are indispensable agents in metabolism because their phosphoric anhydride bonds are a source of chemical 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 metabolism
Page 333 What Are Nucleic Acids?
Nucleic acids: linear polymers of nucleotides linked 3’ to 5’ by phosphodiester bridges (bond) ---DNA (deoxyribonucleic acid) ---RNA (ribonucleic acid)
Phosphodiester bond Page 333
3.d-GACG. Notation for Nucleic Acid Structure Page 334 1.GACG 2.pGpApCpG vs GpApCpGp 3.d-GACG.
What Are the Different Classes of Nucleic Acids? Page 334 DNA - one type, one purpose RNA – several types, multiple purposes ribosomal RNA - the basis of structure and function of ribosomes messenger RNA - carries the message for protein synthesis transfer RNA - carries the amino acids for protein synthesis Others: Small nuclear RNA Small non-coding RNAs
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2.[A]=[T];[C]=[G];[pyrimidine]=[purine] Page 335 & 336 1.Antiparallel 2.[A]=[T];[C]=[G];[pyrimidine]=[purine]
Chargaff’s Data Held the Clue to Base Pairing Page 335 Chargaff’s Data Held the Clue to Base Pairing
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Page 337 Nucleosome: the basic unit of chromatin structure
Page 337 Nucleosome: the basic unit of chromatin structure
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Do the Properties of DNA Invite Practical Applications? Page 339 The molecular recognition between DNA strands can create a molecule with mechanical properties different from single-stranded DNA DNA double helices are relatively rigid rods DNA chains have been used to construct nanomachines capable of simple movements such as rotation and pincerlike motions More elaborate DNA-based devices can act as motors walking along DNA tracks
DNA Tweezers – A Simple DNA Nanomachine Page 339
mRNA Page 338 heterogeneous nuclear RNA=hn RNA Intron exon
Page 338 heterogeneous nuclear RNA=hn RNA (also called Precursor mRNA =pre-mRNA) intron: nucleotide sequence in an RNA molecule that is part of the primary transcript but not the mature, functional RNA molecule exon: nucleotide sequence in a primary RNA transcript that is preserved in the mature, functional RNA molecule
Prokaryotic vs Eukaryotic mRNAs Page 338 (polycistronic)operon (monocistronic) Important message : Protein this word revise to polypeptide
polycistronic mRNA: an mRNA molecule that Page 338 polycistronic mRNA: an mRNA molecule that codes for more than one polypeptide monocistronic mRNA: an mRNA molecule that codes for one polypeptide
rRNA Page 339 & 340 S (sedimentation coefficient)=10-13 sec
Page 339 Sedimentation coefficients are a measure of the velocity with which a particle sediments in a centrifugal force field. Sedimentation coefficients are expressed in Svedbergs (symbolized S), named to honor The Svedberg, developer of the ultracentrifuge. One S=10-13 sec.
Unusual Bases in rRNA Page 340
tRNA Page 340 aminoacyl-tRNA synthetase codon for alanine:5’-GCC-3’ anticodon in tRNA:3’-CGG-5’
Transfer RNAs Carry Amino Acids to Ribosomes for Use in Protein Synthesis Page 340 Small polynucleotide chains contain 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-3′-OH. The a.a. is attached in ester linkage to this 3′-OH. Aminoacyl-tRNA molecules are the substrates of protein synthesis
1.Small nuclear RNAs (sn RNAs) Other RNAs Page 341 1.Small nuclear RNAs (sn RNAs) ---found in nucleus of eukaryotic cells ---100-200 nucleotides ---some are methylated or modified ---associate with specific proteins to form small nuclear ribonucleoprotein particles (snRNPs) in nucleus ---involve in the processing of eukaryotic gene transcripts (hn RNA) into mature messenger RNA spliceosome
2.Small RNAs Page 341 ---21-28 nucleotides ---also called noncoding RNAs [ or ncRNAs] ---target DNA or RNA through complementary base paring ---Small RNAs are classified into a number of subclasses (1)small interfering RNAs (si RNAs) (2)micro RNAs (miRNAs) (3)small nucleolar RNAs (snoRNAs)
3. Long Noncoding RNAs (lincRNAs) a class of regulatory RNAs Page 342 3. Long Noncoding RNAs (lincRNAs) a class of regulatory RNAs are sometimes referred to as “long intergenic noncoding RNAs” or “long intervening noncoding RNAs” (lincRNAs). - RNA transcripts greater than 5 kb in size that do not code for proteins play roles in the regulation of chromatin structure and gene repression. Interestingly, some encode short
Page 341 knockdown vs knockout miRNA gene is transcribed into pri-miRNA. Pri-miRNA is processed into hairpin pre-miRNA. Pre-miRNAs are transported to cytoplasm. Pre-miRNAs are processed into short, mature miRNA duplexes. Mature miRNAs complex with RISC-like structure. miRNA/RISC complex binds to target mRNA. mRNA is translationally repressed. knockdown vs knockout 62
Page 341 miRNA Gene Targeting
Page 341 Structure of siRNA
Page 341 RNAi Mechanism
Differences between DNA and RNA: Page 342 Differences between DNA and RNA: 1.DNA contains 2-deoxyribose instead of ribose 2.DNA contains thymine instead of uracil
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RNA Is Susceptible to Hydrolysis by Base, But DNA Is Not Page 343 & 344
Page 343 & 344 *apurinic acid
The Enzymes That Hydrolyze Nucleic Acids Are Phosphodiesterases Page 343 Phosphodiester bond Enzymes that hydrolyze nucleic acids are called nucleases 71
nuclease phosphodiesterase Page 345
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---nucleases(e.g. nuclease S1) Page 345 nuclease : ---DNases ---RNases ---nucleases(e.g. nuclease S1)
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Classification of Restriction Enzyme: Page 345 & 347 Classification of Restriction Enzyme: 1.Type I 2.Type II 3.Type III
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Page 347 44=256 46=4096 protruding ends