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 phosphorylgroups 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 DiversePhysiologic 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 ANALOGSARE 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
Supercoiling of DNA.
DNA Exists in Relaxed &Supercoiled Forms
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