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 ¿-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
