Outline

Introduction

Outlines of Pathways in Nucleotide Metabolism

> Biosynthetic Routes: De Novo and Salvage Pathways (Figure 22.1)

> Nucleic Acid Degradation and the Importance of Nucleotide Salvage (Figure 22.2, Diagram)

> PRPP: A Central Metabolite in De Novo and Salvage Pathways (Diagram 1, #2)

De Novo Biosynthesis of Purine Nucleotides

> Early Studies on De Novo Purine Synthesis (Figure 22.3, Diagram)

> Purine Synthesis from PRPP to Inosinic Acid (Figure 22.4, Figure 22.5)

> Synthesis of ATP and GTP from Inosinic Acid (Figure 22.6, Diagram 1, #2)

> Utilization of Adenine Nucleotides in Coenzyme Biosynthesis

Purine Degradation and Clinical Disorders of Purine Metabolism

> Formation of Uric Acid (Figure 22.7, Figure 22.8)

> Excessive Accumulation of Uric Acid: Gout (Figure 22.9, Figure 22.4)

> Dramatic Consequences of a Severe HGPRT Deficiency: Lesch-Nyhan Syndrome

> Unexpected Consequences of Defective Purine Catabolism: Immunodeficiency (Diagram)

Pyrimidine Nucleotide Metabolism

> De Novo Biosynthesis of the Pyrimidine Ring (Figure 22.10)

> Control of Pyrimidine Biosynthesis in Bacteria

> Multifunctional Enzymes in Eukaryotic Pyrimidine Synthesis (Diagram)

> Salvage Synthesis and Pyrimidine Catabolism (Figure 22.11)

Deoxyribonucleotide Biosynthesis and Metabolism (Figure 22.12)

> Reduction of Ribonucleotides to Deoxyribonucleotides

> > Structure of Ribonucleotide Reductase (Figure 22.13)

> > Mechanism of Ribonucleotide Reduction (Figure 22.14, Figure 22.15)

> > Source of Electrons for rNDP Reduction (Figure 22.16, Table 22.1)

> > Regulation of Ribonucleotide Reductase Activity (Figure 22.13, Table 22.2)

> Biosynthesis of Thymine Deoxyribonucleotides (Figure 22.17, Figure 22.18)

> Deoxyuridine Nucleotide Metabolism

> Salvage Routes to Deoxyribonucleotide Synthesis (Figure 22.17)

Thymidylate Synthase: A Target Enzyme for Chemotherapy (Diagram, Figure 22.20, Figure 22.22, Diagram)

Virus-Directed Alterations of Nucleotide Metabolism (Diagram, Figure 22.23)

Biological and Medical Importance of Other Nucleotide Analogs

> Nucleotide Analogs as Chemotherapeutic Agents

> > Antiviral Nucleoside Analogs (Diagram)

> > Purine Salvage as a Target

> > Folate Antagonists (Figure 22.18)

> Nucleotide Analogs and Mutagenesis (Figure 22.24)

> Nucleotide-Metabolizing Enzymes as Selectable Genetic Markers (Diagram)