Transcript Nucleotides
Nucleotides BIOMEDICAL IMPORTANCE • Building blocks of nucleic acids • Part of many coenzymes • Donors of – Phosphoryl groups (eg, ATP or GTP) – Sugars (eg,UDP- or GDP-sugars) – Lipid (eg, CDP-acylglycerol) • Regulatory nucleotides – cAMP and cGMP • Control of oxidative phosphorylation – by ADP • Allosteric regulation of enzyme activity – by ATP, AMP, and CTP BIOMEDICAL IMPORTANCE • For therapy – Chemotherapy of cancer and AIDS – Suppressors of the immune response during organ transplantation Classification • • • • PURINES PYRIMIDINES NUCLEOSIDES NUCLEOTIDES Tautomerism of the oxo and amino keto-enol and amine-imine tautomerism • Nucleoside – Diphosphates – Triphosphates • The sugar moiety – D-ribose or 2-deoxy-Dribose • Nucleoside triphosphates – have high group transfer potential • Participate in covalent bond syntheses. • Cyclic phosphodiesters – cAMP and cGMP • Intracellular second messengers Ribonucleosides Additional phosphoryl groups linked by acid anhydride bonds The syn and anti conformers of adenosine differ with respect to orientation about the N-glycosidic bond. Bases, nucleosides, & nucleotides. Nucleic Acids Also Contain Additional Bases • 5-methylcytosine • 5-hydroxymethylcytosine • Mono- and di-N-methylated adenine & guanine – Mammalian messenger RNAs uncommon naturally occurring pyrimidines and purines. • Function – Oligonucleotide recognition – Regulating the half-lives of RNAs • Free nucleotides – Hypoxanthine, xanthine, and uric acid – Intermediates in the catabolism Posttranscriptional modification • Pseudouridine (Ψ) • Methylation by S-adenosylmethionine of a UMP of preformed tRNA forms TMP Nucleotides Serve Diverse Physiologic Functions • • • • Protein synthesis Nucleic acid synthesis Regulatory cascades Signal transduction pathways Physiologic functions • As precursors of nucleic acids • Transducer of free energy – ATP • The second messenger – cAMP • Adenosine 3′-phosphate-5′-phosphosulfate • Methyl group donor 3′-phosphate-5′-phosphosulfate (PAPS) S-Adenosylmethionine Uridine diphosphate glucose (UDPGlc). • Energy source for protein synthesis – GTP • UDP-sugar derivatives – Sugar epimerizations – Biosynthesis of glycogen, glucosyl disaccharides, and the oligosaccharides of glycoproteins and proteoglycans • UDP-glucuronic acid. – Conjugation • Bilirubin • Drugs • CTP – Biosynthesis of phosphoglycerides – Sphingomyelin • Coenzymes Many coenzymes and related compounds are derivatives of adenosine monophosphate. Flavin adenine dinucleotide (FAD). Nicotinamide adenine dinucleotide (NAD). * Shows the site of phosphorylation in NADP. * Shows the site of acylation by fatty acids. • Nucleotides Are Polyfunctional Acids • Nucleotides Absorb Ultraviolet Light – Close to 260 nm SYNTHETIC NUCLEOTIDE ANALOGS ARE USED IN CHEMOTHERAPY • Altered in – Heterocyclic ring – The sugar moiety • Inhibition of enzymes – Treatment of hyperuricemia • Incorporation into nucleic acids • Suppress immunologic rejection – Organ transplantation POLYNUCLEOTIDES • Linked by a 3′ → 5′ phosphodiester bond to form the “backbone” of RNA and DNA • RNAs are far less stable than DNA • Polynucleotides Are Directional Macromolecule – “5′- end” or the “3′- end” – the 5′- end is at the left Polynucleotides Have Primary Structure • Base sequence – Compact notation • pGpGpApTpCpA • GGATCA DNA Contains Four Deoxynucleotides Double-stranded DNA Formation of hydrogen bonds between complementary bases in double-stranded DNA Base pairing DNA Exists in Relaxed & Supercoiled Forms Supercoiling of DNA. Negative and positive supercoils. extent of DNA packaging in metaphase chromosomes Important structural elements of a yeast chromosome • One of the hallmarks of living organisms is their ability to reproduce. • DNA contains the genetic information The interrelationship of DNA,RNA & Protein