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Nucleotide Structure

Nucleotide Structure. Sugars. Sugar + base = nucleoside. Sugar + base + phosphate(s) = nucleotide. Bases. De Novo Purine Nucleotide Synthesis. Begin with ribose 5-phosphate Base constructed by series of reactions that contribute carbon and nitrogen atoms. Synthesis Of PRPP.

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Nucleotide Structure

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  1. Nucleotide Structure Sugars Sugar + base = nucleoside Sugar + base + phosphate(s) = nucleotide Bases

  2. De Novo Purine Nucleotide Synthesis • Begin with ribose 5-phosphate • Base constructed by series of reactions that contribute carbon and nitrogen atoms

  3. Synthesis Of PRPP • PRPP synthetase adds pyrophosphate to ribose 5-phosphate • PRPP involved in pyrimidine synthesis and salvage pathways • Inhibited by AMP, GMP, IMP

  4. Synthesis Of IMP • IMP is “parent” purine • Committed step: • glutamine:PRPP amidotransferase • Inhibited by AMP, GMP, IMP • Inhibitors of IMP synthesis • Folic acid analogs • Sulfonamides

  5. IMP To AMP And GMP • Each conversion by a different two step pathway • End product of each pathway inhibits first reaction • AMP synthesis requires GTP; GMP synthesis requires ATP

  6. NMPs To NDPs And NTPs • NMPs → NDPs by different base-specific kinases (adenylate kinase, guanylate kinase, etc.) • NDPs → NTPs by nucleoside diphosphate kinase • ATP is source of transferred phosphate

  7. Salvage Pathway For Purines • Purines reconverted to nucleotides • Base added to PPRP by APRT or by HGPRT

  8. Degradation Of Purine Nucleotides • Guanosine- remove sugar, deaminate, oxidize to uric acid • Adenosine- deaminate, remove sugar, oxidize to xanthine then uric acid

  9. Gout • Hyperuricemia can cause uric acid crystals to form in joints • Contributing factors • certain inherited metabolic disorders • diet rich in meat and seafood • chronic kidney disease • cancers that cause abnormal cell turnover • chemotherapy treatments that cause rapid cell death • Treatment with allopurinol

  10. Adenosine Deaminase Deficiency • Severe combined immunodeficiency involving T and B cells • Buildup of deoxyadenosine, which leads to buildup of dATP • dATP inhibits ribonucleotidereductase, DNA synthesis

  11. Pyrimidine Synthesis • Base made first and then added to sugar • Base constructed by reactions that contribute carbon and nitrogen atoms

  12. Synthesis Of OMP & UMP • Committed step- CPS II, inhibited by UTP, activated by ATP & PPRP • Synthesis of orate “parent” pyrimidine & addition to PRPP

  13. UTP To CTP • Amination of UTP

  14. NDPs To dNDPs • Reduction of nucleoside diphosphates to deoxy forms • Catalyzed by ribonucleotide reductase; dNTPs inhibit • Thioredoxin coenzyme serves as hydrogen donor

  15. dUMP To dTMP • Thymidylate synthase catalyzes methylation of dUMP • N5,N10-methylene THF contributes methyl group

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