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Functions of Nucleotide: 1.Responsible for transmission of genetic informations 2. Act as energy currency 3.Carrier molecule for a broad spectrum of functional moieties 4.constituent of coenzyme 5.metabolic regulators Page 813
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Biosynthesis of Nucleotides De novo pathways Salvage pathways Page 813
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Nitrogen Waste Is Excreted by Birds Principally as the Purine Analog, Uric acid Page 814
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The Metabolic Origin of the Nine Atoms in the Purine Ring System Page 814
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The de novo Pathway for Purine Synthesis Page 814 & 815 Committed step 4 57 9 AMP, ADP, ATP GMP, GDP, GTP 9
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Page 816
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Page 815 8 3
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Page 816 Also involve in histidine biosynthesis 1 2
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Page 816 Folate and Tetrahydrofolate (THF) dihydrofolate reductase
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Page 816 Tetrahydrofolate (THF) and One-Carbon Units.
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Page 816 & 817
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Folate- Analogs as Anticancer and Antimicrobial Agents Page 818 (folic acid antagonist)
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Page 818 (anti-bacterial agent)
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The Synthesis of AMP and GMP from IMP Page 819 Reciprocal stimulation
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The Regulatory Circuit Controlling Purine Biosynthesis Page 820 feed-forward activation
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ATP-Dependent Kinases Form Nucleoside Diphosphates and Triphosphates from the Nucleoside Monophosphates AMP + ATP 2ADP Adenylate kinase GMP + ATP Guanylate kinase GDP + ADP GDP + ATP Nucleoside diphosphate kinase GTP + ADP Page 820
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Degradation of Purines NMP + H 2 O Nucleoside + Pi Nucleoside+ H 2 O Base + ribose Nucleoside+ Pi Base + ribose-1-phosphate nucleosidase Nucleoside phosphorylase Page 821 & 822 nucleotidase
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The Salvage Pathway for Purine Synthesis Page 821 1.base nucleotide Adenine Adenine phosphoribosyltransferase (APRT) PRPP PPi AMP Hypoxanthine Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) PRPP PPi IMP Guanine Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) PRPP PPi GMP
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Page 821 Purine Salvage by the HGPRT Reaction
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The Salvage Pathway for Purine Synthesis Page 821 2.nucleoside nucleotide Adenosine Adenosine kinase ATPADP AMP 3.base nucleoside nucleotide Hypoxanthine + ribose 1- phosphate inosine + Pi Hypoxanthine + deoxyribose 1- phosphate inosine + Pi Nucleoside phosphorylase
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The Major Pathways of Purine Catabolism Lead to Uric Acid in Animals Page 824
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Page 826
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Gout 痛風 ---Inflammation of joints is caused by a deposition of urate crystals from the blood ---Can usually be controlled with diet Page 825
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Lesch-Nyhan Syndromes: HGPRT Deficiency Leads to a Severe Clinical Disorder Page 822
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The De novo Pyrimidine Biosynthesis Page 826
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Page 827
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Committed step
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UMP Synthesis Leads to Formation of Two Most Prominent Ribonucleotides—UTP and CTP UMP + ATP Nucleotide monophosphate kinase UDP + ADP UDP + ATP Nucleoside diphosphate kinase UTP + ADP Page 828
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CTP Synthesis from UTP Page 828
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Regulatoion of Pyrimidine Synthesis in E. coli and Animals Page 830
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The Salvage Pathway for Pyrimidine Synthesis *nucleoside nucleotide Uridine Cytidine Uridine-cytidine kinase ATPADP UMP CMP Page 829 + ADP
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Pyrimidine Degradation Page 830
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Formation of Deoxyribonucleotide Page 831
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Page 832
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R1 Page 832 R2
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Regulation of Deoxynucleotide Biosynthesis Page 833
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Page 835
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UMP UDP UTP CTP CTP synthetase CDP dCDP dCTP dUDP dUMP dCMP dCMP deaminase dTMP dTDP dTTP Thymidylate synthase Page 833 & 834
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dCMP deaminase thymidylate synthase Page 833 & 834 dUTPase
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Page 834
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Page 836
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Page 818 (anti-bacterial agent)
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Fluoro-Substituted Pyrimidines in Cancer Chemotherapy, Fungal Infections, and Malaria Page 835
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Severe Combined Immunodeficiency Syndrome─A Lack of Adenosine Deaminase is One Cause of This Inherited Disease Page 823 *ADA: adenosine deaminase
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