Nucleotides Chemistry

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






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






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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

Science

Nucleotides Chemistry