Nucleotide Structure
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Transcript of Nucleotide Structure
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SugarsSugar + base = nucleoside
Bases
Sugar + base + phosphate(s) = nucleotide
Nucleotide Structure
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De Novo Purine Nucleotide Synthesis
• Begin with ribose 5-phosphate• Base constructed by series of reactions that contribute
carbon and nitrogen atoms
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Synthesis Of PRPP
• PRPP synthetase adds pyrophosphate to ribose 5-phosphate• PRPP involved in pyrimidine synthesis and salvage pathways• Inhibited by AMP, GMP, IMP
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• IMP is “parent” purine• Committed step:
– glutamine:PRPP amidotransferase
– Inhibited by AMP, GMP, IMP
• Inhibitors of IMP synthesis
– Folic acid analogs– Sulfonamides
Synthesis Of IMP
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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
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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
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•Purines reconverted to nucleotides•Base added to PPRP by APRT or by HGPRT
Salvage Pathway For Purines
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Degradation Of Purine Nucleotides
• Guanosine- remove sugar, deaminate, oxidize to uric acid• Adenosine- deaminate, remove sugar, oxidize to xanthine then uric acid
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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
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Adenosine Deaminase Deficiency
• Severe combined immunodeficiency involving T and B cells
• Buildup of deoxyadenosine, which leads to buildup of dATP
• dATP inhibits ribonucleotide reductase, DNA synthesis
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Pyrimidine Synthesis
• Base made first and then added to sugar• Base constructed by reactions that
contribute carbon and nitrogen atoms
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Synthesis Of OMP & UMP
• Committed step- CPS II, inhibited by UTP, activated by ATP & PPRP• Synthesis of orate “parent” pyrimidine & addition to PRPP
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UTP To CTP
• Amination of UTP
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NDPs To dNDPs
• Reduction of nucleoside diphosphates to deoxy forms• Catalyzed by ribonucleotide reductase; dNTPs inhibit• Thioredoxin coenzyme serves as hydrogen donor
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dUMP To dTMP
• Thymidylate synthase catalyzes methylation of dUMP• N5,N10-methylene THF contributes methyl group