NucleotidesStructureand Functions F ti

AtifH.Khirelsied
B.Sc.,M.Sc.,Ph.D.Biochemistry

FacultyofMedicine InternationalUniversityofAfrica International University of Africa

Thenitrogenousbases
Derivatives of the heterocyclic nitrogenous bases, Derivativesoftheheterocyclicnitrogenousbases, purine andpyrimidine Thepurines areadenine(A)andguanine(G) Thepyrimidines arethymine(T),cytosine(C)and uracil (U)

Thenitrogenousbases

Thenucleosides
Thenucleosidesconsistofapurine orpyrimidine base linkedtoacarbohydrate. linked to a carbohydrate I Innucleicacids,nucleosidesarecoupledtoDriboseor l i id l id l d D ib 2'deoxyDribosethrougha19,Nglycosidic bond

Thenucleosides

Thenucleotides
Thenucleotidesconsistofapurine orpyrimidine base linkedtoaphophosugar. linked to a phopho sugar

Nucleoside

Nucleotide

Thenucleotides

Thenomenclatureofnucleosidesandnucleotides

Thenucleosides e uc eos des

Consistofapurineorpyrimidinebaselinkedtoa carbohydrate(sugar) carbohydrate (sugar)

Innucleicacids,nucleosidesarecoupledtoDriboseor 2'deoxyDribosethrougha19,Nglycosidic bond.

Thebiologicalroleofthenucleotides
1. 2. 3. 4. 4 5. 6. 7. Buildingblocksofnucleicacids. Energytransduction Buildingblocksofcoenzymes. Signaling,2 messengers. Signaling 2nd messengers Neurotransmitters Regulatoryallosteric modulators Activatedprecursorsinbiosynthesis

Theroeofnucleotidesinenergytransfer
Thedi andtriphosphatesofnucleotidesarelinked anhydride withhighG0' . h d id ith hi h G ATPistheuniversalenergymoleculeinmostreactionsin livingcell

ThecyclicAMP
The3'5'cyclicadenosinemonophosphate,cAMP isa 2nd messengerinhormonalsignaltransduction.

Theadenosine derivatives

ThecyclicGMP
Cyclic GMP (cGMP) is also involved as a second messenger CyclicGMP(cGMP)isalsoinvolvedasasecondmessenger molecule

Thesyntheticnucleotideanalogues
Syntheticnucleotideanaloguesareusedfortherapeutic h l d l df h purposes. InterferewithDNAsynthesis,(antitumoragents). I Immunesuppressors. Competitiveinhibitorsofenzymes Competitive inhibitors of enzymes

Thesyntheticnucleotideanalogues
Theanaloguescommonlyusedinantitumor chemotherapyinclude: chemotherapy include: o 6mercaptopurine, o 5fluorouracil, , o 5iodo2'deoxyuridine o 6thioguanine.

6mercaptopurine

Thesyntheticnucleotideanalogues
Azidothymidine (AZT) anddideoxyinosine (ddI) are usedtointerferewiththereplicationofHIV used to interfere with the replication of HIV

Azidothymidine (AZT)

dideoxyinosine (ddI)

Goutiscausedbyhyperuricemia
Uric acid is the end product of purine catabolism Uricacid istheendproductofpurine It is scarcely soluble in water thus precipitates in joints Itisscarcelysolubleinwaterthusprecipitatesinjoints andsofttissuescausinginflammation

Thesyntheticnucleotideanalogues
Allopurinol,apurine analogsresembleshypoxanthine, inhibitsxanthine oxidase,isusedfortreatmentof inhibits xanthine oxidase is used for treatment of hyperuricemia(gout)

Allopurinol,

Thesyntheticnucleotideanalogues
Azathioprine isnucleotideanaloguesusedtosuppress theimmunesystemandreducetransplantrejection. th i t d d t l t j ti

Azathioprine

Nucleotidesarebuildingblocksofcoenzymes
Nicotinamide Adenine Dinucleotide ( i l id (NAD) isa ) coenzymethatcontains purine nucleotide

Nucleotidesarebuildingblocksofcoenzymes
Nicotinamide AdenineDinucleotide Phosphate(NADP) isacoenzymethatcontainspurine nucleotide h l d

Nucleotidesarebuildingblocksofcoenzymes
Flavin AdenineDinucleotide (FAD) isacoenzymethat ( ) h containspurine nucleotide

Nucleotidesareactivatedmetabolicintermediates
Uridine diphosphate glucoseisanintermediateinthe syntesis ofglycogen t i f l

Uridine diphosphate glucose

TheSadenosylmethionine
Sadenosylmethionine istheactivated methioninewhichservesasamethyl donorinmethylationreactions.

Naturalpurines
Caffeineis1.3.7trimetylxanhine.

Theobromine
Caffeine

Theophylline