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
Biosynthesis of Nucleotides De novo pathways Salvage pathways Page 813
Nitrogen Waste Is Excreted by Birds Principally as the Purine Analog, Uric acid Page 814
The Metabolic Origin of the Nine Atoms in the Purine Ring System Page 814
The de novo Pathway for Purine Synthesis Page 814 & 815 Committed step AMP, ADP, ATP GMP, GDP, GTP 9
Page 816
Page
6 1
Page 816 Also involve in histidine biosynthesis 1 2
Page 816 Folate and Tetrahydrofolate (THF) dihydrofolate reductase
Page 816 Tetrahydrofolate (THF) and One-Carbon Units.
Page 816 & 817
Folate- Analogs as Anticancer and Antimicrobial Agents Page 818 (folic acid antagonist)
Page 818 (anti-bacterial agent)
The Synthesis of AMP and GMP from IMP Page 819 Reciprocal stimulation
The Regulatory Circuit Controlling Purine Biosynthesis Page 820 feed-forward activation
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
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
The Salvage Pathway for Purine Synthesis Page 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
Page 821 Purine Salvage by the HGPRT Reaction
The Salvage Pathway for Purine Synthesis Page 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
The Major Pathways of Purine Catabolism Lead to Uric Acid in Animals Page 824
Page 826
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
Lesch-Nyhan Syndromes: HGPRT Deficiency Leads to a Severe Clinical Disorder Page 822
The De novo Pyrimidine Biosynthesis Page 826
Page 827
Committed step
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
CTP Synthesis from UTP Page 828
Regulatoion of Pyrimidine Synthesis in E. coli and Animals Page 830
The Salvage Pathway for Pyrimidine Synthesis *nucleoside nucleotide Uridine Cytidine Uridine-cytidine kinase ATPADP UMP CMP Page ADP
Pyrimidine Degradation Page 830
Formation of Deoxyribonucleotide Page 831
Page 832
R1 Page 832 R2
Regulation of Deoxynucleotide Biosynthesis Page 833
Page 835
UMP UDP UTP CTP CTP synthetase CDP dCDP dCTP dUDP dUMP dCMP dCMP deaminase dTMP dTDP dTTP Thymidylate synthase Page 833 & 834
dCMP deaminase thymidylate synthase Page 833 & 834 dUTPase
Page 834
Page 836
Page 818 (anti-bacterial agent)
Fluoro-Substituted Pyrimidines in Cancer Chemotherapy, Fungal Infections, and Malaria Page 835
Severe Combined Immunodeficiency Syndrome─A Lack of Adenosine Deaminase is One Cause of This Inherited Disease Page 823 *ADA: adenosine deaminase