Slide 1: PURINES AND PYRIMIDINES PRESENTED BY
JAHIRUL ISLAM TALUKDAR
AL-AMEEN COLLEGE OF PHARMACY. HISTORY : In 1868 Frederich Miescher isolated nucleic acid (then called nuclein ) from pus cells.
Albrecht kossel differentiated RNA and DNA in 1882.
Altmann introduced the term nucleic acid in 1889.
In 1906, kossel described the 4 bases in nucleic acid. HISTORY Slide 3: Albrecht kossel FRIEDRICH MIESCHER PURINES AND PYRIMIDINES : Purines and pyrimidines are Nitrogen containing heterocycles, cyclic compouneds whose rings contain both carbon and other elements.
The planar character of purines and pyrimidines facilitates their close association or stacking which stabilizes double stranded DNA. PURINES AND PYRIMIDINES Slide 5: Purines
Pyrimidines PURINE BASES : The purine bases present in RNA and DNA are the same: adenine and Guanine.
Adenine is 6-amino purine and guanine is 2-amino, 6-oxy purine. PURINE BASES PYRIMIDINE BASES : The pyrimidine bases present in nucleic acids are cytosine, thymine and Uracil. PYRIMIDINE BASES Slide 8: NUCLEOSIDES
NUCLEOTIDES NUCLEOSIDES : Nucleosides are derivatives of purines and pyrimidines.
Nucleosides are formed when bases are attached to the pentose sugar ,D-ribose or 2-deoxy D-ribose.
Adenosine Guanosine Cytidine Uridine NUCLEOSIDES Slide 10: All the bases are attached to the corresponding pentose sugar by a beta N-glycosidic bond between the 1st carbon of the pentose sugar and N-9 of a purine or N-1 of a pyrimidine.
It may be noted that nucleosides with purine bases have the suffix SINE while pyrimidine nucleosides end with DINE.
Uracil combines with ribose only and thymine with deoxy ribose only. NUCLEOTIDES : These are phosphate esters of nucleosides.
Base + pentose sugar+ phosphoric acid is a nucleotide.
The esterification usually occurs at the 5th or 3rd hydroxyl group of the pentose sugar.
Nucleoside diphosphate contains one high energy bond and triphosphates have two high energy bond. NUCLEOTIDES NUCLEOTIDE : NUCLEOTIDE Slide 13: ATP is the universal energy currency.
It is formed during oxidative processes by trapping the released energy in the high enrgy phosphate bond.
The monomeric units of DNA are held in polymeric form by 3’-5’ phosphodiester bridges. WATSON AND CRICK MODEL OF DNA : WATSON AND CRICK MODEL OF DNA DIFFERENCE BETWEEN DNA & RNA : DIFFERENCE BETWEEN DNA & RNA Slide 18: BIO-SYNTHESIS OF
PURINE NUCLEOTIDE Slide 21: METABOLISM
OF PURINE Slide 23: SYNTHESIS OF PYRIMIDINE NUCLEOTIDE Slide 25: METABOLISM OF PYRIMIDINES Slide 27: ALLOPURINOL It is a structural analogue of hypoxanthine and is classified as xanthine oxidase inhibitor
1,5-dihydro-4-H-pyrazole [3,4-d] pyrimidine-4-one. SYNTHESIS OF ALLOPURINOL : SYNTHESIS OF ALLOPURINOL MECHANISM OF ACTION : It has been observed that the drug is not uricosuric, but it does inhibit the production of uric acid by way of blocking categorically the biochemical reactions that are essentially involved immediately preceding uric acid formation . Hence it also inhibits xanthine oxidase which is exclusively responsible for the conversion of hypoxanthine to xanthine and of xanthine ultimately to uric acid. MECHANISM OF ACTION USES : Treatment of chronic GOUT.
Minimises the risk of the formation of uric acid calculi.
-100 to 200 mg 2 or 3 times a day. USES XANTHINE OXIDASE : Xanthine oxidase (bovine milk enzyme) is an important enzyme that converts hypoxanthine to xanthine then to uric acid (in degradation of purine nucleotides). XANTHINE OXIDASE STRUCTURE OF XANTHINE OXIDASE : It is a large molecule having molecular weight approx. 270,000.
Each enzyme unit contains :
2 flavin molecules (FAV).
2 molybdenum atoms.
8 iron atoms.
Molybdenum atoms contained as molybdenum co-factors and are active sites of enzymes. STRUCTURE OF XANTHINE OXIDASE FAD : FAD Slide 35: Iron atoms are part of [2Fe-2S] feredoxin iron – sulphur clusters and participates in electron transfer reactions.
When xanthine is oxidised , oxygen is transferred from Mo to xanthine.
Reformation of the active Mo occurs by the addition of water.
Oxygen atom introduced to the substrate by xanthine oxidase, originates from water rather from di–oxygen (O2). Slide 37: COMPLICATION. References : References Harper’s Illustrated Biochemistry – by : Robert K. Murray, Daryl K. Granner, Peter A. Mayes, Victor W. Rodwell; 26th edition; Lange Medical Publication; Pg no. – 286 – 301.
Biochemistry – by : U. Satyanarayana; 2nd Revised Edition June 2002; Uppala Author Publisher Interlinks; Pg no. – 405 – 418.
Text book of Biochemistry,for medical students-by:DM Vasudevan and sreekumari S, 4TH edition,jaypee publication pg no-385-395.
Foye’s principles of medicinal chemistry , sixth edition ,by Thomas.L.lemke, David A.Williams, Victoria F. Roche, S.William Zito.,pg no. 1045-1055 Slide 39: THANK YOU