Handbook of Neurochemistry and Molecular Neurobiology: Amino Acids and Peptides in the Nervous System

Cover
......Page 1
748.pdf......Page 2
Glutamine, Glutamate, and GABA: Metabolic Aspects......Page 10
2 Content of Glutamate, Glutamine, and GABA in Different Brain Regions......Page 11
4.1 Glutamate......Page 12
4.2 GABA......Page 13
4.3.1 Glutamine......Page 14
4.3.2 Ammonia Homeostasis in the Glutamate-Glutamine Cycle......Page 17
4.5 Ammonia Toxicity......Page 18
5.2 Aminotransferases......Page 19
6.1 Pyruvate Carboxylase......Page 20
7.2 Phosphate-Activated Glutaminase......Page 21
8.2 GABA aminotransferase......Page 22
References......Page 23
Serine, Glycine, and Threonine......Page 32
2.1 l-Serine Biosynthesis......Page 34
2.2.1 Glycine and One-Carbon Group Production by l-Serine Hydroxymethyltransferases......Page 35
2.2.3 l-Serine and Synthesis of Glycine and d-Serine......Page 36
2.5 l-Threonine Utilization......Page 37
3.1 l-Serine During Central Nervous System Development......Page 38
3.2.2 d-Serine and Glycine......Page 40
3.4.1 3-Phosphoglycerate Dehydrogenase Deficiency......Page 41
3.4.3 Disorders Associated with Alterations in Serine Metabolism......Page 42
4.1 Glycine During Central Nervous System Development......Page 43
4.2.1 Glycine Receptors......Page 44
4.2.2 Glycine and N-Methyl-d-Aspartate Neurotransmission......Page 45
4.3.1 Hyperekplexia......Page 46
4.3.3 Disease States with a Secondary Elevation of Glycine......Page 47
5 l-Threonine in the Central Nervous System......Page 48
5.2.3 Clinical Use of l-Threonine......Page 49
References......Page 50
Histidine......Page 56
2 Histidine Transport and Uptake in Brain......Page 57
4 Histidine as Histamine Precursor......Page 59
5.1 Mechanism and Consequences of Histidinemia......Page 60
5.2 Brain Disorders Related to Histidinemia......Page 61
5.3 Portocaval Anastomosis and Histidinemia......Page 62
References......Page 63
Aromatic Amino Acids in the Brain......Page 68
1 Introduction......Page 69
2 Sources of Aromatic Amino Acids......Page 70
3 Plasma Concentrations of the Aromatic Amino Acids......Page 71
3.1.1 Tryptophan Dioxygenase and Indoleamine Dioxygenase......Page 75
3.2 Plasma Tyrosine......Page 78
3.2.1 Tyrosine Aminotransferase......Page 79
Properties......Page 81
4 Brain Tryptophan and Tyrosine......Page 82
4.1 Transport of Plasma Tryptophan and Tyrosine into the Brain......Page 83
4.2 Brain Tryptophan......Page 84
Regulation......Page 86
4.3 Brain Tyrosine......Page 87
Regulation......Page 88
5.1 Precursor Availability and Neurotransmission......Page 89
5.1.1 Neurons That Lack Multisynaptic or Autoreceptor-Based Feedback Loops......Page 90
5.1.3 Neurons That Normally Release Variable Quantities of Neurotransmitter Per Firing Without Engaging Feedback Responses......Page 91
5.1.4 Physiologic Situations in Which Neurons Undergo Sustained Increases in Firing Frequency......Page 92
5.1.5 Neurologic Diseases That Cause Either a Decreased Number of Synapses of Decreased Transmitter Release Per Unit Time......Page 93
5.2 Brain Tryptophan and Serotonin......Page 94
5.3 Brain Tyrosine and the Catecholamines......Page 96
Acknowledgements......Page 97
References......Page 98
Arginine, Citrulline, and Ornithine......Page 108
2.1 Tissue and CSF......Page 109
2.2 Cellular Localization......Page 110
3 Metabolism and Transport......Page 111
3.1.1 Arginine......Page 112
3.1.2 Citrulline......Page 113
3.2.1 Arginine......Page 114
3.2.2 Citrulline and Ornithine......Page 115
3.3.1 Arginine......Page 116
4.1 Arginine......Page 117
4.2 Citrulline and Ornithine......Page 118
References......Page 119
Branched Chain Amino Acids (BCAAs) in Brain......Page 126
2 Branched Chain Amino Acid Metabolism......Page 127
4 Branched Chain Amino Acids as Nitrogen Donors in the Central Nervous System......Page 130
5 Role of BCAA in de novo Glutamate Synthesis and the Branched Chain Aminotransferase (BCAT) Cycle Hypothesis......Page 131
6.2 The Mitochondrial Enzymes BCATm and Branched Chain a-Keto Acid Dehydrogenase (BCKD)......Page 134
6.3 The BCAT Cycle and GABA Metabolism......Page 135
Acknowledgments......Page 136
References......Page 137
Sulfur-Containing Amino Acids......Page 142
1 Introduction......Page 143
4 Cellular and Regional Localization of Excitatory SAAs in the Brain......Page 144
5 Excitatory SAAs as Neurotransmitters......Page 147
5.2 Activation of Receptors......Page 148
6 Transport of SAAs......Page 150
6.1 Uptake of SAAs by the Glutamate Transporter Family......Page 151
6.2 Transport of l-Cysteine by the ASC System......Page 152
6.4 Interrelationship Between the Glutamate Transporters and the xc- Exchanger in the Uptake of l-Cystine......Page 153
7 Other Roles for Excitatory SAAs......Page 154
8.3 Toxicity of l-Cysteine......Page 155
8.4 l-Homocysteine Neurotoxicity......Page 156
8.6 Gliotoxicity......Page 157
References......Page 158
Taurine......Page 164
2.1 Occurrence and Distribution......Page 165
2.2 Metabolism......Page 167
3.1 Uptake......Page 168
3.2 Transporters......Page 170
3.3.2 Basal Release......Page 171
3.3.3 Release Under Cell-Damaging Conditions......Page 172
3.3.4 Taurine Release and Cell-Volume Regulation......Page 174
3.3.5 Potassium-Stimulated Release......Page 176
3.3.7 Mechanisms of Stimulated Release......Page 177
3.3.8 Ethanol Effects......Page 179
3.3.9 Ammonia Stimulation......Page 180
4.1.1 Interactions with gamma-Aminobutyrate Receptors......Page 181
4.1.2 Interactions with Glycine Receptors......Page 182
4.1.3 Long-Lasting Synaptic Potentiation......Page 183
4.1.4 Putative Taurine Receptors......Page 184
4.2.1 Antinociceptive Effects and Thermoregulation......Page 185
4.2.2 Seizures and Epilepsy......Page 186
4.2.3 Neuroprotective Actions......Page 187
4.2.4 Retina......Page 189
5 Taurine Derivatives......Page 191
Acknowledgments......Page 193
References......Page 194
Neurobiology of D-Amino Acids......Page 216
2 Neurobiology of D-Serine......Page 217
2.1 D-Serine: A Physiological Regulator of NMDA Receptors......Page 218
2.2 Serine Racemase: Biosynthesis of D-Serine......Page 220
2.4 D-Serine Metabolism and Transport......Page 221
2.5 D-Serine Release......Page 223
2.7 D-Serine and NMDA Receptor Dysfunction......Page 224
2.8 Neuromodulator or Neurotransmitter?......Page 225
3.1 D-Aspartate in the Nervous and Endocrine System......Page 226
3.4 Biosynthesis of D-Aspartate......Page 227
4 Conclusions and perspectives......Page 228
References......Page 229
Amino Acids and Brain Volume Regulation: Contribution and Mechanisms......Page 234
1 Introduction......Page 235
2.1 Amino Acid Levels in Brain During Volume Adjustment to Hyposmolarity......Page 236
2.2 The Mechanism of Regulatory Volume Decrease......Page 237
2.2.1 The Amino Acid Efflux Pathway......Page 238
2.2.2 The Osmotransduction Signaling......Page 239
2.3 Hyposmolarity-Induced Release of Amino Acids from Nerve Endings......Page 240
2.4 Volume Regulation After Gradual Decreases in Osmolarity: The Relevance of Amino Acids......Page 242
3 Isosmotic Swelling......Page 244
3.1 Amino Acids and Isosmotic Swelling......Page 245
4.1.1 Hypertonicity and Osmolyte Transporters......Page 248
4.1.2 Hypertonicity and Osmolyte Biosynthesis......Page 250
5.2 Apoptosis......Page 251
References......Page 253
Urea Cycle Enzymopathies......Page 258
1 Experimental Urea Cycle Enzymopathies......Page 260
2.1 Amino Acids......Page 261
2.3 The Cholinergic System......Page 262
3 Serotonin......Page 263
5.1 Sodium Benzoate, Phenylacetate......Page 264
5.4 Liver Transplantation......Page 265
References......Page 266
Ammonia Toxicity in the Central Nervous System......Page 270
1 Introduction: Issues Under Consideration......Page 271
2 Hyperammonemic Encephalopathies: Clinical Conditions and Model Systems......Page 272
3 Penetration of Ammonia from Blood to Brain and Changes in the Blood-Brain Barrier Function......Page 273
4.1 Morphological Changes, Disturbances of Energy Metabolism, and Oxidative Stress in Astrocytes......Page 274
4.2 Changes in Astrocyte-Neuron Interaction Resulting in the Imbalance Between the Excitatory (Glutamatergic) and.........Page 276
4.3.1 NMDA Receptor-Mediated Nitrosative and Oxidative Stress......Page 277
4.4.1 Accumulation of Glutamine and Other Osmolytes: Osmotic Versus Metabolic Effects and Critical Coupling to Bioenergetic.........Page 278
5 Derangements Resulting from Increased Accumulation in Brain of Aromatic Amino Acids: Catecholaminergic Transmission......Page 279
6 Protection Against Neurotoxic Effects of Ammonia......Page 280
References......Page 281
Disorders of Amino Acid Metabolism......Page 286
1.1 History......Page 288
1.5 Autosomal Recessive Inheritance......Page 289
1.7 Diagnosis......Page 290
2.2 Acute Versus Chronic Encephalopathies......Page 291
2.4 Effects on Brain Amino Acid Uptake......Page 292
2.6 Aminoacidopathies and Neurotransmitters......Page 293
3.1.1 Phenylalanine Hydroxylase Deficiency......Page 294
4.1 Maple Syrup Urine Disease......Page 296
5 Disorders of Glycine Metabolism: Nonketotic Hyperglycinemia......Page 298
6.1.1 Cystathionine Synthase Deficiency......Page 300
6.1.3 Methylenetetrahydrofolate Reductase Deficiency......Page 303
7.1 Ureagenesis......Page 304
7.1.3 Ornithine Transcarbamylase Deficiency......Page 306
7.1.8 Lysinuric Protein Intolerance......Page 307
8.1 Glutathione Metabolism......Page 308
9.1.1 Pyridoxine Dependency......Page 309
References......Page 310
N-Acetylaspartate andN-Acetylaspartylglutamate......Page 314
1 Introduction......Page 316
1.2 N-Acetylaspartylglutamate......Page 317
2.2 Use of NAA as a Neuron Marker......Page 318
4.2.1 NAA Dynamic Model Variable Rate Functions......Page 320
4.2.3 NAA Dynamic Values in Human Brain......Page 321
5.2.1 Myelin Formation Hypothesis......Page 322
5.3.1 Release of Hydrophilic NAA to the ECF......Page 323
6 NAA Function as an MWP and Its Role in the Etiology of Canavan Disease......Page 324
7.2.1 Structural, Metabolic, and Dynamic Relationships Between NAA and NAAG......Page 326
7.3 A Functional Relationship Between NAA and NAAG......Page 327
8.2.1 The Glu Moiety Is the Neuron Signal to Astrocytes......Page 328
8.2.4 Rate and Availability of the Glu Entity to Astrocytes from NAAG......Page 329
NAAG as a Source of Glu......Page 330
BOLD Measurements......Page 331
Nature of Neuron-Astrocyte Chemical Signals......Page 332
8.2.7 Relationship of mGluR Activation and Hyperemia to BOLD Imaging......Page 333
9.3 Target Cell for NAAG and Its Obligated Water......Page 334
10.1 The Primary Functions for NAA and NAAG Are Osmoregulatory......Page 335
10.5.1 The NAA-NAAG System Functions as a Unit......Page 336
Result of Delays in Microcirculatory Responses......Page 337
Neuron Information Processing and the NAA-NAAG System......Page 338
10.6.2 Temporal Interaction of NAAG Dynamics and the fMRI BOLD Response......Page 342
11.1 Canavan Disease......Page 344
11.2 Hypoacetylaspartia......Page 345
12.2.1 Dynamic Measures in Normal Humans......Page 346
13 Conclusions......Page 347
14 Epilogue......Page 348
References......Page 349
Low Molecular Weight Peptides......Page 356
1 Special Aspects of Oligopeptide Biology......Page 357
3 Is There a General Role of Peptides in the Brain?......Page 358
4 Peptide Purification......Page 359
5 Endogenous Peptides......Page 360
5.3 Diketopiperazines......Page 361
5.4 Opioids......Page 362
References......Page 363
764.pdf......Page 368