Chm 635-14

Chm 635-14 - NUCLEOTIDE METABOLISM Nucleotides UDP-glucose...

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1 Nucleotides DNA, RNA ATP, GTP cAMP, cGMP NAD + , NADP + , FMN, FAD, Coenzyme A NUCLEOTIDE METABOLISM Nucleotide biosynthetic pathways are tremendously important as intermediate points for therapeutic agents. Many cancer drugs block steps in nucleotide biosynthesis, particularly steps in the synthesis of DNA precursors. UDP-glucose
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2 1. All organisms and cells can synthesize purine and pyrimidine nucleotides. 2. In non-dividing cells, nucleotide biosynthesis is almost exclusively devoted to the synthesis of ribonucleotides and various nucleotide cofactors. 3. In dividing cells, deoxyribonucleotides are required for DNA replication. 1. De-novo synthesis of purines and pyrimidines nucleotides 2. Salvage Pathway. 3. Conversion of purines and pyrimidines ribonucleotides into the corresponding deoxy forms. 4. Biological Degradation of nucleotides. Purine Pyrimidine Potentially toxic materials Readily metabolized products Excreted
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3 Biosynthetic routes: De novo and salvage pathways De novo pathways Almost all cell types have the ability to synthesize purine and pyrimidine nucleotides from low molecular weight precursors in amounts sufficient for their own needs. The de novo pathways are almost identical in all organisms. Salvage pathways Most organisms have the ability to synthesize nucleotides from nucleosides or bases that become available through the diet or from degradation of nucleic acids. In animals, the extracellular hydrolysis of ingested nucleic acids represents the major route by which bases become available. The biosynthetic origins of purine ring atoms. De Novo Salvage 1. Amino acids and Bicarbonate 2. Unlike pyrimidines, purines bases are assembled already attached to the ribose ring. 1. Purine bases released by hydrolytic degradation of nucleic acids and nucleotides, can be salvaged and recycled. 2. This salvage pathway is especially noted for the energy they save.
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4 De novo Synthesis of Purine Nucleotides Uric acid and the major purines The biosynthetic origins of purine ring atoms.
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5 5-Phosphoribosyl-1-pyrophosphate (Purines and Pyrimidines) Ribonucleotides
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Chm 635-14 - NUCLEOTIDE METABOLISM Nucleotides UDP-glucose...

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