Nucleotide Synthesis PDF

Metabolism of purines and pyrimidines DR:ADIL KHALIL PURINE BASES PYRIMIDINE BASES  Structure of purine and pyrimidine nucleotides nucleotide = ester of phosphoric acid and a nucleoside nucleoside = N-containing base + monosaccharide b-N-glycosidic bond be...

Metabolism of purines and pyrimidines DR:ADIL KHALIL PURINE BASES PYRIMIDINE BASES  Structure of purine and pyrimidine nucleotides nucleotide = ester of phosphoric acid and a nucleoside nucleoside = N-containing base + monosaccharide b-N-glycosidic bond between base and saccharide nucleotide bases: aromatic heterocycles Ø purines: pyrimidine + imidazol ring Ø pyrimidines: pyrimidine ring ribonucleoside deoxyribonucleoside N-glycosidic bond ribonucleosides deoxyribonucleoside  Ribonucleotides * N-glycosidic bond * ester bond * anhydride bond ribonucleotide deoxyribonucleotide  Classification of nucleotides purine nucleotides: contain adenine, guanine, hypoxanhine or xanthine pyrimidine nucleotides: contain cytosine, uracil or thymine ribonucleotides (saccharide = ribose) deoxyribonucleotide (saccharide = deoxyribose)  Synthesis of purine nucleotides de novo = new building of a nucleotide rings salvage reactions = synthesis from bases or nucleosides Ø less energy need than for de novo synthesis Ø they inhibit de novo synthesis Ø substrates: a) base (adenine, guanine, hypoxanthine) PRPP b) ribonucleosides ATP  Synthesis of purine nucleotides de novo (I) high consumption of energy (ATP) cytoplasm of many cells, mainly in the liver substrates: * 5-phosphoribosyl-1-diphosphate (= PRDP = PRPP) * amino acids (Gln, Gly, Asp) * tetrahydrofolate derivatives, CO2 coenzymes: * tetrahydrofolate (= THF) * NAD+  Synthesis of purine nucleotides C Y T O P L A S M  IMP GMP AMP  Activation of folate (reduction) Dihydrofolate reductase can be inhibited by Methotrexate  Regulation of nucleotide synthesis PRPP-synthetase is inhibited by both purine and pyrimidine nucleoside di- and triphosphates nucleotide synthesis: feed back inhibition Inhibitors for purine synthesis: sulfonamides,methotrexate,Trimethoprim  Synthesis of pyrimidine nucleotides de novo = new building of a nucleotide rings salvage reactions = synthesis from bases or nucleosides Ø substrates: a) * base * PRPP b) * ribonucleosides * ATP  Synthesis of pyrimidine nucleotides de novo (I) cytoplasm of cells (exception: one enzyme is found at mitochondria /dihydroorotate-DH) substrates: * carbamoyl phosphate (Gln,CO2,2ATP) * aspartate * PRPP * methylene-THF (only for thimidine) carbamoyl phosphate is formed in urea synthesis as well (only in mitochondria of hepatocytes)  Synthesis of pyrimidine nucleotides C mitochondrion Y T O P L A S M  Regulation of nucleotide synthesis regulatory enzyme activation inhibition glutamine-PRPP PRPP IMP, GMP, amidotransferase AMP (purines) (allosteric inhibition) carbamoylphosphate PRPP UTP synthetase II ATP = cytosolic (pyrimidines) Thanks