Nucleic acids and Nucleotides - PowerPoint Presentation

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Nucleic acids and Nucleotides

By: Preeti S. Salve

KLE

College of Pharmacy,

Belagavi

A constituent Unit of KLE Academy of Higher Education and Research

Nehru Nagar,

Belagavi

–

590 010, Karnataka, India

Phone:

0831-2471399;

Fax:

0831-2472387;

Web:

http

://

www.klepharm.edu

E

-mail:

principal@klepharm.edu

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Nucleic acids

Nucleic acids are required for the storage and expression of genetic informationTwo types –Deoxyribonucleic acid (DNA)Ribonucleic acid (RNA)

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Functions of nucleic acids

DNA is the chemical basis of heredity and may be regarded as the reserve bank/repository of genetic informationIt has maintained the identity of different species

of organisms over millions of

years

DNA controls all the cellular functions

DNA

is

organized

into

genes

-

the

fundamental

units

of

genetic

information

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Genes control the protein synthesis through the mediation of RNA

The interrelationship between DNA, RNA and proteins constitutes the central dogma of molecular biology or the central dogma of life

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Components of nucleic acids

Nucleic acids are the polymers of nucleotides held by 3' and 5' phosphate bridgesNucleotides (monomeric units) are building blocks of nucleic acids

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NUCLEOTIDES

Nucleotide = nitrogenous base + pentose sugar + phosphateNucleoside = base + sugarTherefore, nucleotide = nucleoside + phosphate

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Nitrogenous bases are aromatic heterocyclic compounds

They are of two types - purines and pyrimidinesPurines - Numbered anticlockwisePyrimidines

- Numbered clockwise

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Structures

Purines

Pyrimidines

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DNA contains thymine (T) whereas RNA contains

uracil (U)Purines and pyrimidines with oxo

functional group exist as tautomers

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Sugars of nucleic acids

RNADNA

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Bases in nucleic acids

AdenineGuanine CytosineUracil

RNA

DNA

Adenine

Guanine

Cytosine

Thymine

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Cyclic nucleotides

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Biological significance of nucleotides

Nucleotides serve as monomeric precursor of RNA and DNAPurine nucleotides serve as

hihgh energy sources e.g. ATPPurine nucleotides form regulatory signals e.g. cyclic AMP

Purine

nucleotides act as components of coenzymes e.g. FAD, NAD, etcPyrimidine nucleotides serve as high energy intermediates e.g. UDP glucose and UDP galactose in carbohydrate metabolism and CDP-acyl

glycerol in lipid synthesis

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Nucleic acids

DNA (Deoxyribonucleic acid)RNA (Ribonucleic acid)

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DNA

It is a polymer of deoxyribonucleotidesComposed of monomeric units namely

deoxyadenylate (dAMP), deoxyguanylate

(dGMP),

deoxycytidylate (dCMP) and deoxythymidylate (dTMP

)

The

monomeric

deoxvnucleotides

in DNA are held together by 3',5'-phosphodiester bridge

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Chargaff’s rule of DNA composition

Erwin Chargaff (1940) observed that -DNA had equal no. of adenine and thymine residues (A=T)And equal no. of guanine and cytosine residues (G=C)This rule is followed only by double stranded DNA and RNA

Not followed by single stranded DNA and RNA

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DNA double helix

The double helical structure of DNA was proposed by lames Watson and Francis Crick in 1953 (Nobel Prize, 1962)

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Denaturation

of DNA strandsThe two strands of DNA helix are held together by hydrogen bonds Disruption of hydrogen bonds (by change in pH or increase in temperature) results in the separation of

polynucleotides strandsThis phenomenon of loss of helical structure of DNA is known as

denaturation

Renaturation (reannealing) - separated complementary DNA strands can form a double helix

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The two strands of DNA helix are held together by hydrogen bonds

Disruption of hydrogen bonds (by change in pH or increase in temperature) results in the separation of polynucleotides strandsThis phenomenon of loss of helical structure of DNA is known as denaturation

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RNA

RNA is a polymer of ribonucleotides held together by 3',5'-phosphodiester bridges

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Types of RNA

1. Messenger RNA (mRNA) : 5-10%2. Transfer RNA (IRNA) : 10-20%3. Ribosomal RNA (rRNA) : 50-80%

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PURINE BIOSYNTHESIS

Many compounds contribute to the purine ring of the nucleotides

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Synthesis of AMP and GMP

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CATABOLISM OF NUCLEOTIDES

Degradation of purine nucleotidesThe end product of

purine metabolism in humans is uric acid

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Disorders of

purine metabolismNormal concentration of uric acid in the serum of adults is in the range of 3-7 mg/dlHyperuricemia refers to an elevation in the serum uric acid concentration

Gout is a metabolic disease associated with overproduction of uric acid

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Primary gout:

It is an inborn error of metabolism due to overproduction of uric acid This is mostly related to increased synthesis of purine nucleotidesSecondary gout: It is due to various diseases causing increased synthesis or decreased excretion of uric acid

Increased degradation of nucleic acids (hence more uric acid formation) is observed in various cancers (leukemias, polycythemia, lymphomas, etc.) psoriasis and increased tissue breakdown (

trauma,starvation etc

.

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Treatment of gout

Drug of choice for the treatment of primary gout is allopurinolIt is a structural analog of hypoxanthine that competitively inhibits the enzyme xanthine oxidaseAllopurinol

is further oxidized to alloxanthine by xanthine oxidaseAlloxanthine

, in turn, is a more effective inhibitor of xanthine oxidaseThis is termed as

suicide inhibition

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