Plant Nucleotide Metabolism

Professor Hiroshi Ashihara is an Emeritus Professor at the Ochanomizu University, Tokyo, Japan. Dr Iziar A. Ludwig is a Postdoctoral Research Associate at the School of Medicine and Life Sciences, University Rovira I Virgili, Reus, Spain. Professor Alan Crozier is an Honorary Senior Research Fellow at the Department of Nutrition, University of California, Davis, CA, USA and the School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.

Preface xv

Part I General Aspects of Nucleotide Metabolism 1

1 Structures of Nucleotide-Related Compounds 3

1.1 Introduction 3

1.2 Nomenclature and Abbreviations of Nucleotide-Related Compounds 3

1.3 Chemical Structures of Nucleotide-Related Compounds 5

1.3.1 Purines 5

1.3.1.1 Purine Bases 5

1.3.1.2 Purine Nucleosides 6

1.3.1.3 Purine Nucleotides 7

1.3.2 Pyrimidines 8

1.3.2.1 Pyrimidine Bases 9

1.3.2.2 Pyrimidine Nucleosides 9

1.3.2.3 Pyrimidine Nucleotides 10

1.3.3 Pyridines 11

1.4 Summary 11

References 11

2 Occurrence of Nucleotides and Related Metabolites in Plants 13

2.1 Purines and Pyrimidines 13

2.1.1 Concentration of Purine and Pyrimidine Nucleotides 14

2.1.2 Concentration of Purine and Pyrimidine Bases and Nucleosides 16

2.2 Pyridine Nucleotides 17

2.2.1 Concentration of Pyridine Nucleotides 17

2.2.2 Concentration of Nicotinate and Nicotinamide 18

2.3 Concentration of Cytokinins 18

2.4 Alkaloids Derived from Nucleotides 18

2.5 Summary 19

References 19

3 General Aspects of Nucleotide Biosynthesis and Interconversions 21

3.1 Introduction 21

3.2 De Novo Biosynthesis of Ribonucleoside Monophosphates 21

3.3 Interconversion of Nucleoside Monophosphates, Nucleoside Diphosphates, and Triphosphates 23

3.3.1 Nucleoside-Monophosphate Kinase 23

3.3.2 Specific Nucleoside-Monophosphate Kinases 24

3.4 Conversion of Nucleoside Diphosphates to Nucleoside Triphosphates 24

3.4.1 ATP Synthesis by Electron Transfer Systems 25

3.4.2 Substrate-Level ATP Synthesis 26

3.4.3 Nucleoside-Diphosphate Kinase 26

3.5 Biosynthesis of Deoxyribonucleotides 29

3.6 Nucleic Acid Biosynthesis 29

3.7 Supply of 5-Phosphoribosyl-1-Pyrophosphate 30

3.8 Supply of Amino Acids for Nucleotide Biosynthesis 33

3.9 Nitrogen Metabolism and Amino Acid Biosynthesis in Plants 33

3.10 Summary 34

References 35

Part II Purine Nucleotide Metabolism 39

4 Purine Nucleotide Biosynthesis De Novo 41

4.1 Introduction 41

4.2 Reactions and Enzymes 43

4.2.1 Synthesis of Phosphoribosylamine 44

4.2.2 Synthesis of Glycineamide Ribonucleotide 46

4.2.3 Synthesis of Formylglycineamide Ribonucleotide 46

4.2.4 Synthesis of Formylglycinamidine Ribonucleotide 47

4.2.5 Synthesis of Aminoimidazole Ribonucleotide 47

4.2.6 Synthesis of Aminoimidazole Carboxylate Ribonucleotide 48

4.2.7 Synthesis of Aminoimidazole Succinocarboxamide Ribonucleotide 48

4.2.8 Synthesis of Aminoimidazole Carboxamide Ribonucleotide 49

4.2.9 Synthesis of IMP via Formamidoimidazole Carboxamide Ribonucleotide 49

4.2.10 Synthesis of AMP 50

4.2.11 Synthesis of GMP 51

4.3 Summary 52

References 52

5 Salvage Pathways of Purine Nucleotide Biosynthesis 55

5.1 Introduction 55

5.2 Characteristics of Purine Salvage in Plants 56

5.3 Properties of Purine Phosphoribosyltransferases 59

5.3.1 Adenine Phosphoribosyltransferase 59

5.3.2 Hypoxanthine/Guanine Phosphoribosyltransferase 59

5.3.3 Xanthine Phosphoribosyltransferase 62

5.4 Properties of Nucleoside Kinases 62

5.4.1 Adenosine Kinase 62

5.4.2 Inosine/Guanosine Kinase 64

5.4.3 Deoxyribonucleoside Kinases 64

5.5 Properties of Nucleoside Phosphotransferase 65

5.6 Role of Purine Salvage in Plants 66

5.7 Summary 66

References 66

6 Interconversion of Purine Nucleotides 71

6.1 Introduction 71

6.2 Deamination Reactions 71

6.2.1 Routes of Deamination of Adenine Ring 73

6.2.2 AMP Deaminase 73

6.2.3 Routes of Deamination of Guanine Ring 74

6.2.4 Guanosine Deaminase 75

6.3 Dephosphorylation Reactions 75

6.4 Glycosidic Bond Cleavage Reactions 76

6.4.1 Adenosine Nucleosidase 76

6.4.2 Inosine/Guanosine Nucleosidase 78

6.4.3 Non-specific Purine Nucleosidases 78

6.4.4 Recombinant Non-Specific Nucleosidases 78

6.5 In Situ Metabolism of 14C-Labelled Purine Nucleotides 79

6.5.1 Metabolism of Adenine Nucleotides 79

6.5.2 Metabolism of Guanine Nucleotides 80

6.6 In Situ Metabolism of Purine Nucleosides and Bases 80

6.6.1 Metabolism of Adenine and Adenosine 82

6.6.2 Metabolism of Guanine and Guanosine 83

6.6.3 Metabolism of Hypoxanthine and Inosine 84

6.6.4 Metabolism of Xanthine and Xanthosine 84

6.6.5 Metabolism of Deoxyadenosine and Deoxyguanosine 85

6.7 Summary 88

References 89

7 Degradation of Purine Nucleotides 95

7.1 Introduction 95

7.2 (S)-Allantoin Biosynthesis from Xanthine 97

7.2.1 Xanthine Dehydrogenase 99

7.2.2 Urate Oxidase 100

7.2.3 Allantoin Synthase 101

7.3 Catabolism of (S)-Allantoin 101

7.3.1 Allantoinase 103

7.3.2 Allantoate Amidohydrolase 104

7.3.3 (S)-Ureidoglycine Aminohydrolase 104

7.3.4 Allantoate Amidinohydrolase 105

7.3.5 Ureidoglycolate Amidohydrolase 105

7.3.6 (S)-Ureidoglycolate-urea Lyase 105

7.3.7 Urease 105

7.4 Purine Nucleotide Catabolism in Plants 106

7.5 Accumulation and Utilization of Ureides in Plants 107

7.5.1 Ureides in Plant Tissues and Xylem Sap 107

7.5.2 Role of Ureides in Nitrogen Storage and Transport 109

7.5.3 Role of Ureides in Germination and Development of Seeds 109

7.5.4 Ureide Formation in Nodules of Tropical Legumes 110

7.5.5 Other Role of Ureides in Plants 110

7.6 Summary 111

References 111

Part III Pyrimidine Nucleotide Metabolism 117

8 Pyrimidine Nucleotide Biosynthesis De Novo 119

8.1 Introduction 119

8.2 Reactions and Enzymes of the De Novo Biosynthesis 121

8.2.1 Synthesis of Carbamoyl-phosphate 121

8.2.2 Formation of Carbamoyl-aspartate 123

8.2.3 Formation of Dihydroorotase from Carbamoyl-aspartate 123

8.2.4 Formation of Orotate from Dihydroorotate 124

8.2.5 Synthesis of UMP from Orotate 125

8.2.6 Synthesis of CTP from UTP 126

8.3 Control Mechanism of De Novo Pyrimidine Ribonucleotide Biosynthesis 127

8.3.1 Fine Control of the De Novo Pathway 127

8.3.2 Coarse Control of the De Novo Pathway 129

8.4 Biosynthesis of Thymidine Nucleotide 129

8.4.1 Formation of dUMP 129

8.4.2 Conversion of UMP to dUMP via dUTP 130

8.4.3 Conversion of dUMP to dTMP 130

8.4.4 Thymidine Monophosphate Kinase 131

8.5 Summary 131

References 131

9 Salvage Pathways of Pyrimidine Nucleotide Biosynthesis 137

9.1 Introduction 137

9.2 Characteristics of Pyrimidine Salvage in Plants 137

9.3 Enzymes of Pyrimidine Salvage 139

9.3.1 Uracil Phosphoribosyl Transferase 140

9.3.2 Uridine/Cytidine Kinase 142

9.3.3 Thymidine Kinase 143

9.3.4 Deoxyribonucleoside Kinase 144

9.3.5 Nucleoside Phosphotransferase 144

9.4 Role of Pyrimidine Salvage in Plants 145

9.5 Summary 146

References 146

10 Interconversion of Pyrimidine Nucleotides 149

10.1 Introduction 149

10.2 Deaminase Reactions 149

10.2.1 Cytidine Deaminase 149

10.2.2 Cytosine Deaminase 152

10.2.3 Deoxycytidylate Deaminase 152

10.3 Nucleosidase and Phosphorylase Reactions 152

10.3.1 Uridine Nucleosidase 152

10.3.2 Thymidine Phosphorylase 153

10.4 In Situ Metabolism of 14C-Labelled Pyrimidines 153

10.4.1 Metabolic Fate of Orotate 154

10.4.2 Metabolic Fate of Uridine and Uracil 154

10.4.3 Metabolic Fate of Cytidine and Cytosine 156

10.4.4 Metabolic Fate of Deoxycytidine 157

10.4.5 Metabolic Fate of Thymidine 158

10.5 Summary 159

References 160

11 Degradation of Pyrimidine Nucleotides 165

11.1 Introduction 165

11.2 Enzymes Involved in the Degradation Routes of Pyrimidines 166

11.2.1 Dihydropyrimidine Dehydrogenase 167

11.2.2 Dihydropyrimidinase 167

11.2.3 𝛽-Ureidopropionase 168

11.3 The Metabolic Fate of Uracil and Thymine 168

11.4 Summary 169

References 170

Part IV Physiological Aspects of Nucleotide Metabolism 173

12 Growth and Development 175

12.1 Introduction 175

12.2 Embryo Maturation 175

12.3 Germination 180

12.3.1 Purine Metabolism in Germination 180

12.3.2 Pyrimidine Metabolism in Germination 183

12.4 Organogenesis 185

12.5 Breaking Bud Dormancy 186

12.6 Fruit Ripening 186

12.7 Storage Organ Development and Sprouting 186

12.8 Suspension-Cultured Cells 187

12.8.1 Nucleotide Pools 187

12.8.2 Nucleotide Biosynthesis 188

12.8.3 Nucleotide Availability 188

12.9 Molecular Studies 189

12.10 Summary 189

References 189

13 Environmental Factors and Nucleotide Metabolism 195

13.1 Introduction 195

13.2 Effect of Phosphate on Nucleotide Metabolism 195

13.3 Effect of Salts on Nucleotide Metabolism 199

13.4 Effect of Water Stress 202

13.5 Effect of Wound Stress 202

13.6 Effect of Iron Deficiency 205

13.7 Effect of Light 206

13.8 Summary 206

References 206

Part V Purine Alkaloids 211

14 Occurrence of Purine Alkaloids 213

14.1 Introduction 213

14.2 Chemical Structure of Purine Alkaloids 213

14.3 Occurrence of Purine Alkaloids in Plants 215

14.3.1 Purine Alkaloids in Tea and Related Species 215

14.3.2 Purine Alkaloids in Coffee and Related Species 218

14.3.3 Purine Alkaloids in Maté 220

14.3.4 Purine Alkaloids in Cacao and Related Species 221

14.3.5 Purine Alkaloids in Cola Species 223

14.3.6 Purine Alkaloids in Guaraná and Related Species 223

14.3.7 Purine Alkaloids in Citrus Species 224

14.3.8 Purine Alkaloids in Other Plants 225

14.4 Summary 226

References 226

15 Biosynthesis of Purine Alkaloids 231

15.1 Introduction 231

15.2 A Brief History of Caffeine Biosynthesis Research 231

15.3 Caffeine Biosynthesis Pathway 234

15.3.1 N-Methyltransferase Nomenclature 236

15.3.2 Formation of 7-Methylxanthine from Xanthosine 236

15.3.3 7-Methylxanthosine Synthase 237

15.3.4 N-Methylnucleosidase 240

15.3.5 Formation of Caffeine from 7-Methylxanthine 241

15.3.6 Caffeine Synthase 241

15.3.7 Theobromine Synthase 244

15.4 Genes and Proteins of Caffeine Synthase Family 245

15.5 Xanthosine Biosynthesis from Purine Nucleotides 249

15.5.1 De Novo Purine Route 249

15.5.2 Adenosine Monophosphate Route 251

15.5.3 S-Adenosyl-L-methionine Cycle Route 251

15.5.4 Nicotinamide Adenine Diphosphate Catabolism Route 252

15.5.5 Guanosine Monophosphate Route 253

15.6 Summary 253

References 253

16 Physiological and Ecological Aspects of Purine Alkaloid Biosynthesis 259

16.1 Introduction 259

16.2 Physiology of Caffeine Biosynthesis 259

16.2.1 Purine Alkaloid Biosynthesis in Different Species 261

16.2.2 Camellia 261

16.2.3 Coffea 264

16.2.4 Theobroma 264

16.2.5 Maté 266

16.2.6 Guaraná 267

16.2.7 Citrus 268

16.3 Subcellular Localization of Caffeine Biosynthesis 268

16.3.1 Caffeine Synthase 268

16.3.2 The De Novo Route Enzymes 269

16.3.3 The AMP Route Enzymes 270

16.3.4 The SAM Route Enzymes 270

16.3.5 Subcellular Localization and Transport of Intermediates 270

16.4 Regulation of Caffeine Biosynthesis 270

16.5 Ecological Roles of Caffeine 271

16.5.1 Allelopathic Function Theory 271

16.5.2 Effect of Caffeine on Plant Growth 272

16.5.3 Allelopathy in Natural Ecosystems 273

16.5.4 Chemical DefenceTheory 274

16.6 Summary 274

References 275

17 Metabolism of Purine Alkaloids and Biotechnology 281

17.1 Introduction 281

17.2 Metabolism of Purine Alkaloids 281

17.2.1 Methylurate Biosynthesis 281

17.2.2 The Major Pathway of Caffeine Degradation 282

17.2.3 Purine Catabolic Pathways in Alkaloid Plants 284

17.3 Diversity of Purine Alkaloid Metabolism in Plants 285

17.3.1 Coffea Species 285

17.3.2 Camellia Species 286

17.3.3 Maté Species 290

17.3.4 Cacao Species 290

17.3.5 Other Plant Species 290

17.3.6 Bacteria 291

17.4 Biotechnology of Purine Alkaloids 293

17.4.1 Decaffeinated Coffee Plants 293

17.4.2 Decaffeinated Tea Plants 294

17.5 Caffeine-Producing Transgenic Plants 295

17.5.1 Antiherbivore Activity 295

17.5.2 Antipathogen Activity 296

17.6 Summary 298

References 298

Part VI Pyridine Nucleotide Metabolism 301

18 Pyridine (Nicotinamide Adenine) Nucleotide Biosynthesis De Novo 303

18.1 Introduction 303

18.2 Two Distinct Pathways of De Novo Nicotinate Mononucleotide Biosynthesis 303

18.3 The Outline of the De Novo Pathway of NAD Biosynthesis in Plants 304

18.4 Enzymes Involved in De Novo NAD Synthesis in Plants 307

18.4.1 l-Aspartate Oxidase and Quinolinate Synthase 308

18.4.2 Quinolinate Phosphoribosyltransferase 309

18.4.3 Nicotinate Mononucleotide Adenylyltransferase 309

18.4.4 NAD Synthetase 310

18.4.5 NAD Kinase 310

18.5 Summary 310

References 310

19 Pyridine Nucleotide Cycle 315

19.1 Introduction 315

19.2 Pyridine Nucleotide Cycle 315

19.2.1 Major Pyridine Nucleotide Cycles in Plants 317

19.2.2 Alternative Pyridine Nucleotide Cycles in Plants 318

19.2.3 Rate-Limiting Step of the Pyridine Cycle 319

19.3 Catabolism of NAD 320

19.3.1 Reactions from NAD to Nicotinate 320

19.3.2 Degradation of Pyrimidine Ring 320

19.3.3 Nicotinate Conversion to Nicotinate-N-Glucoside and N-Methylnicotinate 321

19.4 Enzymes Involved in NAD Catabolism 321

19.4.1 Direct NAD Cleavage Enzymes 321

19.4.2 NAD Pyrophosphatase 321

19.4.3 5′-Nucleotidase and Nicotinamide Riboside Nucleosidase 322

19.4.4 Nicotinamidase and Nicotinamide Riboside Deaminase 322

19.5 Salvage of Nicotinamide and Nicotinate 323

19.5.1 Nicotinate Phosphoribosyltransferase 323

19.5.2 Nicotinate Riboside Kinase 324

19.6 Summary 325

References 325

Part VII Pyridine Alkaloids 329

20 Occurrence and Biosynthesis of Pyridine Alkaloids 331

20.1 Introduction 331

20.2 Occurrence of Pyridine Alkaloids 333

20.2.1 Trigonelline in Plants 333

20.2.2 Other Pyridine Alkaloids in Plants 334

20.3 Biosynthesis of Pyridine Alkaloids 335

20.3.1 Trigonelline Biosynthesis 335

20.3.2 Nicotinate N-Glucoside Biosynthesis 336

20.3.3 The Diversity of Biosynthetic Reactions 337

20.3.3.1 Ferns 338

20.3.3.2 Gymnosperms 338

20.3.3.3 Angiosperms 339

20.3.3.4 Nicotinate Conjugate Formation 340

20.3.4 Biosynthesis of Ricinine 341

20.3.5 Biosynthesis of Nicotine (Pyridine Ring) 343

20.4 Summary 345

References 345

21 Physiological Aspect and Biotechnology of Trigonelline 351

21.1 Introduction 351

21.2 Physiological Aspect of Trigonelline Biosynthesis 351

21.2.1 Coffee 351

21.2.2 Leguminous Plants 354

21.3 Physiological Aspect of Nicotinate N-Glucoside Biosynthesis 356

21.4 The Role of Trigonelline in Plants 356

21.4.1 Role of Trigonelline as a Nutrient Source 357

21.4.2 Role of Trigonelline as a Compatible Solute 357

21.4.3 Trigonelline and Nyctinasty 358

21.4.4 Cell Cycle Regulation 358

21.4.5 Detoxification of Nicotinate 359

21.4.6 Signal Transduction 360

21.4.7 Role of Host Selection by Herbivores 360

21.5 Biotechnology of Trigonelline 360

21.6 Summary 362

References 363

Part VIII Other Nucleotide-Related Metabolites 367

22 Sugar Nucleotides 369

22.1 Introduction 369

22.2 The Sugar Nucleotide Moiety 370

22.3 Enzymes of Sugar Nucleotide Biosynthesis 371

22.3.1 UDP-Glucose Pyrophosphorylase 371

22.3.2 UDP-Sugar Pyrophosphorylase 374

22.3.3 Sucrose Synthase 376

22.4 Localization of UDP-Glucose-Producing Enzymes 377

22.5 UDP-Glucose-Interconversion 377

22.6 Other Metabolites 379

22.6.1 Cyclic Nucleotides 379

22.6.2 Diadenosine Tetraphosphate 381

22.6.3 Purine Alkaloid Glucosides 382

22.7 Summary 382

References 382

23 Cytokinins 387

23.1 Introduction 387

23.2 Adenosine Phosphate-Isopentenyl Formation 388

23.3 trans-Zeatin Phosphate Synthesis 389

23.4 Formation of Cytokinin Bases 389

23.5 Effect of Nucleotide Enzymes in Cytokinins 390

23.5.1 Cytokinin Inactivation by Adenine Phosphoribosyltransferase 390

23.5.2 Homeostasis of Cytokinin by Adenosine Kinase 392

23.5.3 Endodormancy of Potato and Purine Nucleoside Phosphorylase 392

23.6 New Purine-Related Plant Growth Regulators 392

23.7 Summary 393

References 394

Part IX Dietary Plant Alkaloids, Their Bioavailability, and Potential Impact on Human Health 397

24 Bioavailability and Potential Impact on Human Health of Caffeine, Theobromine, and Trigonelline 399

24.1 Caffeine 399

24.1.1 Dietary Caffeine 399

24.1.2 Bioavailability and Bioactivity of Caffeine 400

24.2 Theobromine 404

24.2.1 Interactions with Flavan-3-ols 404

24.2.2 Toxicity ofTheobromine 406

24.3 Trigonelline 406

24.3.1 Dietary Trigonelline 406

24.3.2 Bioavailability and Bioactivity of Trigonelline 407

24.4 Summary 409

References 409

Index 415