Transcript
Nucleotide ChemistryBAHS 233
GoalsIdentify the basic structure of nucleotides and nucleosides
Identify Nucleotide derivatives and analogues
Familiar with the different biological roles of nucleotides
Content Structure of Nucleotides
Naming of Nucleotides
Biomedical Functions of Nucleotides
Nucleotide Derivatives and Functions
Use Nucleotide Analogues as Drugs
Nucleoside
Sugar
Base
= Sugar + Base
Nucleotide = Nucleoside + Phosphate
Sugar
Base
Phosphate
Nucleoside
Composition of NucleotidesNucleotide = Nucleoside + Phosphate
Glycosidic Bond is a bond between a sugar and another group
Ester Bond
Glycosidic Bond
Ester Bond is C-O-R and the oxygen is bounded to something else
Composition of Nucleotides
Sugar
Bases
Phosphate
• Pentoses (5-C sugars or carbohydrate)• Numbering of sugars is “primed”
Sugars
Ribose : forming Ribonucelotides
Deoxyribose: forming Deoxynucelotides (d-Nucleotides)
Oxygen missing
Sugars(two types
fused five- and six-membered rings
Bases(two types)
Pyrimidines – N 1 forms glycosidic bond with sugarPurines -N 9 forms glycosidic bond with the sugar
six membered rings
Bases( Sub-types)
Adenine A
Guanine G
Thymine T Uracil U
Cytosine C
Pyrimidine Base Structures
Purine Base Structures
Bases Occurrence
Ribonucleotides only
Ribonucleotides & D-nucleotides
D-nucloetides only
• Phosphates can be bonded to either C5 or C3
Phosphate Groups
Ester Bond
• They are linked by an Ester bond
Mono, Di, Tri phosphate Groups
Nucleotide 5’-Monophosphate
Nucleotide 5’- Diphosphate
Nucleotide 5’- Triphosphate
• Purine nucleosides end in “-sine” – Ribonucleoside Deoxynucleoside
• Adenosine Deoxyadenosine• Guanosine Deoxyguanosine
Naming Conventions of Nucleosides
Pyrimidine nucleosides end in “-dine”– Ribonucleoside Deoxynucleoside
• Deoxythymidine • Cytidine Deoxycytidine• Uridine
Start with the nucleoside name from above and add “mono-”, “di-”, or “triphosphate”
Naming Conventions of Nucleotides
Ribonucleotides
PurinesAdenosine monophosphate(AMP), ADP, ATPGuanosine monophosphate(GMP), GDP, GTP
PyrimindinesCytidine Monophosphate, CDP, CTPUridine Monophosphate, UDP, UTP
Naming Conventions of Nucleotides
Deoxynucleotides
PurinesDeoxyadenosine monophosphate (d-AMP), d-ADP, d-ATPd- Guanosine Monophosphate, d-GDP, d-GTP
Pyrimindinesd- Cytidine Monophosphate, d-CDP, d-CTPd- thymidine Monophosphate, d-TDP, d-TPP
Memory Check
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Phosphodiester Bond (linkages)
Nucleotides are joined together by Phosphodiester bonds
ester bond
ester bond
Phosphodiester bond
Voet, Voet & Pratt 2013 Fig 3.3a,b
Nucleic Acids : Polymers of nucleotides
Nucleic acid with deoxy ribose sugars---Deoxyribonucleic acid (DNA)
Nucleic acid with Contains ribose sugar---Ribonucleic acid(RNA)
Memory Check
Nucleoside Derivatives
Adenosine derivatives
Guanosine derivative
Cytidine derivatives
Uridine derivatives
Adenosine Triphosphate (ATP)
3'-5'-Cyclic Adenosine Monophosphate, “(cAMP or cyclic AMP)
Flavin Adenine Dinucleotide (FAD & FMN)
Nicotinaminde Adenine Dinucleotide (NAD+ & NADP)
S-adenosylmethionine (SAM)
Common Adenosine Derivatives
ATP Structure
Adenosine Triphosphate (ATP),
FUNCTIONS
Adenosine Derivatives
1. Energy storage and transfer
2. Release of the third phosphate to produce adenosine diphosphate, or ADP releases energy for cell activity
Cyclic AMP Structure
Cyclic AMP or 3'-5'-cyclic adenosine monophosphate,
FUNCTIONS
Adenosine Derivatives
1. Second messenger in signal transduction
2.Regulate metabolism e.g. glycogen breakdown, lipids breakdown etc
Flavin Adenine Dinucleotide (FAD(H2) & FMN(H2) Structure
Flavin Mononucloetide
(FMN)
Flavin
Coenzyme functioning as carrier of hydrogen and electrons in some redox reactions
sugar
+ H2
Riboflavin(Vit B 2)
FAD
FMN(H2) or FAD(H2)
phosphate
Nicotinamide Adenine DinucleotideNAD (H)+ and NADP(H)+ Structures
+ H
Coenzyme functioning as carrier of hydrogen
and electrons some redox reactions
NADP
NADPH
NAD
Coenzyme A Structure
Coenzyme serving as acyl group – R(CO) carrier in certain enzymatic reactions
S- adenosylmethionine Structure
Methyl (CH3) donor in methylation reactions
Adenosine Triphosphate (ATP)
3'-5'-Cyclic Adenosine Monophosphate, “(cAMP or cyclic AMP)
Flavin Adenine Dinucleotide (FAD & FMN)
Nicotinaminde Adenine Dinucleotide (NAD+ & NADP)
S-adenosylmethionine (SAM)
Common Adenosine Derivatives
Guanosine Triphosphate (GTP),
FUNCTIONS
Guanosine Derivative
1. Energy store
2.Energy source for Protein synthesis and Gluconeogenesis
3. Energy source during elongation stage of translation
Thymidine Derivatives
Ribothymindine
Plays a role thermal stability of transfer RNA
Uracil Derivatives
UDP glucoronate ---- glucuronic acid donor
UDP-glucose-,glucose donor in glycogen synthesis.
UDP-sugar derivatives-----glu, gal, fruc --- used as sugar donors, used in glycoproteins and glycolipids synthesis
Cytidine Derivatives
CMP-N acetylneuraminic acid (CMP-NANA) required for the biosynthesis of glycoproteins
CDP-choline- required for the biosynthesis of sphingolipids (component of cell membrane of brain and nervious tissues).
CTP- required for the biosynthesis of phosphoglycerides (component of cell membrane)
sphingosine
Synthetic Analogues of Nucleotides
An analogue is an organic chemical compound related to another by substitution of atoms with other groups
Chemically synthesized nucleotides used as drugs in clinical therapy
Nucleotide analogues are prepared by altering the base ring or sugar moiety.
Synthetic Analogues of Nucleotides:Anti-tumour agents used in chemotherapy
Interfere with the synthesis of DNA and thereby preferentially kill rapidly dividing cells such as tumor cells.
5-fluorouracil
6- mercaptopurine)
Synthetic Analogues of Nucleotides:Anti-tumour agents used in chemotherapy
Synthetic Analogues of Nucleotides:Anti-Viral agents
Used to interfere with the replication of viruses by terminating DNA synthesis
Lamivudine ----- Hepatitis B
AZT (azidothymidine or zidovudine) - HIV
Synthetic Analogues of Nucleotides:Treatment of Gout
Caused by accumulation of uric acid
Allopurinol is a structural analogue of hypoxanthine is used treat gout
The drug is an inhibitor of the enzyme xanthine oxidase which converts hypoxanthine to uric acid
Biomedical importance of nucleotides
Precursors of nucleic acids, DNA & RNA
Components of important co-enzymes ( like NAD+ and FAD, Co-enzyme A)
Storage and transfer of energy (ATP and GTP )
Storage and transfer of genetic information (DNA & RNA)
Biomedical importance of nucleotides
Synthetic analogues used in medicine e.g. 5-fluorouracil
CTP and UTP are both used in the production of biomolecules
Metabolic rgulators such as cAMP
Memory Check
Memory Check
Ribonucleotides only
Ribonucleotides & D-nucleotides
D-nucloetides only
Adenosine Triphosphate (ATP)
3'-5'-Cyclic Adenosine Monophosphate, “(cAMP or cyclic AMP)
Flavin Adenine Dinucleotide (FAD & FMN)
Nicotinaminde Adenine Dinucleotide (NAD+ & NADP)
S-adenosylmethionine (SAM)
Memory Check
Memory Check
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Guanosine Triphosphate (GTP),
UDP-sugar derivatives; glu, gal, fruc
CMP-N acetylneuraminic acid (NANA)
Cytidine Triphosphate (CTP)
Memory Check
Content
Structure of Nucleotides
Naming of Nucleotides
Biomedical Functions of Nucleotides
Nucleotide Derivatives and Functions
Use Nucleotide Analogues as Drugs
Nucleotide ChemistryBAHS 233
Thank you
Minor Pyrimidine nucleosides
Minor Purine Nucleosides
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