Nucleic acids and Nucleotides By Preeti S Salve
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
Nucleic acids • Nucleic acids are required for the storage and expression of genetic information • Two types – 1. Deoxyribonucleic acid (DNA) 2. Ribonucleic acid (RNA)
Functions of nucleic acids • DNA is the chemical basis of heredity and may be regarded as the reserve bank/repository of genetic information • It 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
• 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
Components of nucleic acids • Nucleic acids are the polymers of nucleotides held by 3' and 5' phosphate bridges • Nucleotides (monomeric units) are building blocks of nucleic acids
NUCLEOTIDES • Nucleotide = nitrogenous base + pentose sugar + phosphate • Nucleoside = base + sugar • Therefore, nucleotide = nucleoside + phosphate
• Nitrogenous bases are aromatic heterocyclic compounds • They are of two types - purines and pyrimidines • Purines - Numbered anticlockwise • Pyrimidines - Numbered clockwise
Structures Purines Pyrimidines
• DNA contains thymine (T) whereas RNA contains uracil (U) • Purines and pyrimidines with oxo functional group exist as tautomers
Sugars of nucleic acids RNA DNA
Bases in nucleic acids RNA DNA 1. Adenine 2. Guanine 3. Cytosine 4. Uracil 4. Thymine
Cyclic nucleotides
Biological significance of nucleotides 1. Nucleotides serve as monomeric precursor of RNA and DNA 2. Purine nucleotides serve as hihgh energy sources e. g. ATP 3. Purine nucleotides form regulatory signals e. g. cyclic AMP 4. Purine nucleotides act as components of coenzymes e. g. FAD, NAD, etc 5. Pyrimidine nucleotides serve as high energy intermediates e. g. UDP glucose and UDP galactose in carbohydrate metabolism and CDP-acyl glycerol in lipid synthesis
Nucleic acids 1. DNA (Deoxyribonucleic acid) 2. RNA (Ribonucleic acid)
DNA • It is a polymer of deoxyribonucleotides • Composed of monomeric units namely deoxyadenylate (d. AMP), deoxyguanylate (d. GMP), deoxycytidylate (d. CMP) and deoxythymidylate (d. TMP) • The monomeric deoxvnucleotides in DNA are held together by 3', 5'-phosphodiester bridge
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
DNA double helix • The double helical structure of DNA was proposed by lames Watson and Francis Crick in 1953 (Nobel Prize, 1962)
Denaturation of DNA strands • The two strands of DNA helix are held together by hydrogen bonds • Disruption of hydrogen bonds (by change in p. H or increase in temperature) results in the separation of polynucleotides strands • This phenomenon of loss of helical structure of DNA is known as denaturation • Renaturation (reannealing) - separated complementary DNA strands can form a double helix
• The two strands of DNA helix are held together by hydrogen bonds • Disruption of hydrogen bonds (by change in p. H or increase in temperature) results in the separation of polynucleotides strands • This phenomenon of loss of helical structure of DNA is known as denaturation
RNA • RNA is a polymer of ribonucleotides held together by 3', 5'-phosphodiester bridges
Types of RNA 1. Messenger RNA (m. RNA) : 5 -10% 2. Transfer RNA (IRNA) : 10 -20% 3. Ribosomal RNA (r. RNA) : 50 -80%
PURINE BIOSYNTHESIS • Many compounds contribute to the purine ring of the nucleotides
Synthesis of AMP and GMP
CATABOLISM OF NUCLEOTIDES Degradation of purine nucleotides The end product of purine metabolism in humans is uric acid
Disorders of purine metabolism • Normal concentration of uric acid in the serum of adults is in the range of 3 -7 mg/dl • Hyperuricemia refers to an elevation in the serum uric acid concentration • Gout is a metabolic disease associated with overproduction of uric acid
Primary gout: • It is an inborn error of metabolism due to overproduction of uric acid • This is mostly related to increased synthesis of purine nucleotides Secondary 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.
Treatment of gout • Drug of choice for the treatment of primary gout is allopurinol • It is a structural analog of hypoxanthine that competitively inhibits the enzyme xanthine oxidase • Allopurinol is further oxidized to alloxanthine by xanthine oxidase • Alloxanthine, in turn, is a more effective inhibitor of xanthine oxidase • This is termed as suicide inhibition
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