Harpers

NUCLEOTIDES / 289ONNH 2CH 3NH5-MethylcytosineONNH 2NHCH 2 OH5-Hydroxymethylcytosine–OOPNH 2NNCH 2OONNOHNH 2 N NO CH 2O– O P ONNH 3 CNCH 3OCH 3OOHOOHNNHNN7Figure 33–9.cAMP, 3′,5′-cyclic AMP, and cGMP.NNHDimethylaminoadenineH 2 Nmammalian messenger RNAs (Figure 33–7). Theseatypical bases function in oligonucleotide recognitionand in regulating the half-lives of RNAs. Free nucleotidesinclude hypoxanthine, xanthine, and uric acid(see Figure 34–8), intermediates in the catabolism ofadenine and guanine. Methylated heterocyclic bases ofplants include the xanthine derivatives caffeine of coffee,theophylline of tea, and theobromine of cocoa (Figure33–8).Posttranslational modification of preformed polynucleotidescan generate additional bases such aspseudouridine, in which D-ribose is linked to C-5 ofuracil by a carbon-to-carbon bond rather than by aβ-N-glycosidic bond. The nucleotide pseudouridylicacid Ψ arises by rearrangement of UMP of a preformedtRNA. Similarly, methylation by S-adenosylmethionineof a UMP of preformed tRNA forms TMP (thymidinemonophosphate), which contains ribose rather than deoxyribose.N7-MethylguanineFigure 33–7. Four uncommon naturally occurringpyrimidines and purines.H 3 CNOCH 3NNNucleotides Serve DiversePhysiologic FunctionsNucleotides participate in reactions that fulfill physiologicfunctions as diverse as protein synthesis, nucleicacid synthesis, regulatory cascades, and signal transductionpathways.Nucleoside Triphosphates Have HighGroup Transfer PotentialAcid anhydrides, unlike phosphate esters, have highgroup transfer potential. ∆ 0 ′ for the hydrolysis of eachof the terminal phosphates of nucleoside triphosphatesis about −7 kcal/mol (−30 kJ/mol). The high grouptransfer potential of purine and pyrimidine nucleosidetriphosphates permits them to function as group transferreagents. Cleavage of an acid anhydride bond typicallyis coupled with a highly endergonic process suchas covalent bond synthesis—eg, polymerization of nucleosidetriphosphates to form a nucleic acid.In addition to their roles as precursors of nucleicacids, ATP, GTP, UTP, CTP, and their derivativeseach serve unique physiologic functions discussed inother chapters. Selected examples include the role ofATP as the principal biologic transducer of free energy;the second messenger cAMP (Figure 33–9); adenosine3′-phosphate-5′-phosphosulfate (Figure 33–10), thesulfate donor for sulfated proteoglycans (Chapter 48)and for sulfate conjugates of drugs; and the methylgroup donor S-adenosylmethionine (Figure 33–11).ONNCH 3Figure 33–8. Caffeine, a trimethylxanthine. The dimethylxanthinestheobromine and theophylline aresimilar but lack the methyl group at N-1 and at N-7, respectively.PAdenine Ribose P O SO2–3Figure 33–10. Adenosine 3′-phosphate-5′-phosphosulfate.