Harpers

SECTION IVStructure, Function, & Replicationof Informational MacromoleculesNucleotides 33Victor W. Rodwell, PhDBIOMEDICAL IMPORTANCENucleotides—the monomer units or building blocks ofnucleic acids—serve multiple additional functions. Theyform a part of many coenzymes and serve as donors ofphosphoryl groups (eg, ATP or GTP), of sugars (eg,UDP- or GDP-sugars), or of lipid (eg, CDP-acylglycerol).Regulatory nucleotides include the second messengerscAMP and cGMP, the control by ADP of oxidativephosphorylation, and allosteric regulation ofenzyme activity by ATP, AMP, and CTP. Syntheticpurine and pyrimidine analogs that contain halogens,thiols, or additional nitrogen are employed for chemotherapyof cancer and AIDS and as suppressors of theimmune response during organ transplantation.PURINES, PYRIMIDINES, NUCLEOSIDES,& NUCLEOTIDESPurines and pyrimidines are nitrogen-containing heterocycles,cyclic compounds whose rings contain bothcarbon and other elements (hetero atoms). Note thatthe smaller pyrimidine has the longer name and thelarger purine the shorter name and that their six-atomrings are numbered in opposite directions (Figure33–1). The planar character of purines and pyrimidinesfacilitates their close association, or “stacking,” whichstabilizes double-stranded DNA (Chapter 36). The oxoand amino groups of purines and pyrimidines exhibitketo-enol and amine-imine tautomerism (Figure 33–2),but physiologic conditions strongly favor the aminoand oxo forms.1N2CHH6 7C 5 N C 8CHCN 4 N93 HPurine3NHC2H4C 5CHN1CH6PyrimidineFigure 33–1. Purine and pyrimidine. The atoms arenumbered according to the international system.Nucleosides & NucleotidesNucleosides are derivatives of purines and pyrimidinesthat have a sugar linked to a ring nitrogen. Numeralswith a prime (eg, 2′ or 3′) distinguish atoms of thesugar from those of the heterocyclic base. The sugar inribonucleosides is D-ribose, and in deoxyribonucleosidesit is 2-deoxy-D-ribose. The sugar is linked to theheterocyclic base via a -N-glycosidic bond, almost alwaysto N-1 of a pyrimidine or to N-9 of a purine (Figure33–3).NH 2 NHO OHFigure 33–2. Tautomerism of the oxo and aminofunctional groups of purines and pyrimidines.286