Index

Acetoacetate, 70 , 88 – gliotoxins and, 148 , 75 Amyotrophic lateral sclerosis, 381–383 – glutamate/glutamine cycle, , 253 Anaplerosis, 2, 8, 10–12 123, 126 Acetyl-L-carnitine, 256 Antiepileptic drugs, 177, 178, 183 – glutamate/pyruvate cycle, AD-Amino acids, discovery, 208 Antinociception, 177 123, 124 Adrenal medulla, 80, 88 Antioxidant, 350, 353, 355, 359–361, – GSH in, 148 Aerobic cells, 349 379, 381–383, 385 – interaction with , 263, Aging, 378–381 Apparent diffusion coefficient, 323 267, 268 Agmatine, 100, 106 Appetite, 82, 86 – lactate, 123, 124 Agonists glutamate receptors, 179, 180 Arginase – localisation of SAAs in, 138 Alanine aminotransferase, 3, 9–11 – immunoreactivity, 105 – morphology of, 265–267, 272 Albumin, 64, 66, 69, 75–77, 85 – isoforms, 105 – oxidative stress in, 262, 265 Alcohol, 170, 182 – release of SAAs from, 139 Alzheimer’s disease, 310, 329, 333, 378, – concentration in brain and CSF, – SAA biosynthesis and 380, 381 100, 101 in, 135 – muscarinic sites, 254 – deimination, 102 – SAA transport into, 141 – type II astrocytosis, 251 – immunohistochemistry, 101 – sodium-calcium exchanger in, 139 Amfonelic acid, 87 – metabolism in astrocytes, Biosynthesis taurine, taurine – g-aminobutyrate receptors, 108, 109 transporter, 160 172, 173 – N-methylated analogues, 100 Blood-brain barrier (BBB), 48, 66, 352, – g-aminobutyric acid (GABA), – proteinogenic amino acid, 109 353, 385 357, 372, 374, 377 – substrate of NOS, 105 Bold signals, 322–324, 333, 335 Amidohydrolase I, 308 (ADC), Brain compartments, 309, 310 Amidohydrolase II, 309, 311, 314, 315, 106, 107 Brain peptides 317, 318, 326, 335, 336 Argininosuccinate – ampholytes, 402 Amino acid, 2–4, 6–11, 349, 350, – localization, 103, 104 – cyclic peptides, 405–407 352–355, 362, 363, 369, 374, 376, Argininosuccinate synthetase – endogenous peptides, 405 378, 381, 383, 384 – immunoreactivity, 103, 104 – endorphins, 407 – aromatic, 61, 62, 85 – localization cellular/subcellular, – exogenous peptides, 408 – branched-chain, 62, 64, 73, 76, 85 103, 104 – exorphins, 408 – glutamate, 118–127 Argininosuccinate, 102–104, 109 – gamma-glutamyl peptides, 406 – large, neutral, 85 Aromatic amino acid decarboxylase – N-substistuted peptides, 404 – isoleucine, 118, 120 (AAAD), 74, 77, 78, 82 – pepetide ‘‘families’’, 405 – leucine, 118, 120–122, 124–127 Aromatic amino acids, 60–62, 85 Brain, 61 f – neutral, 64, 70, 85 ASC transport system Branched-chain amino acids (BCAAs), – valine, 118, 120 – localisation, 141 62, 66, 76, 85 – g-aminobutyric acid (GABA), – subtypes, 143 BCAT nitrogen shuttle in brain, 125 118, 119, 121, 122, 124–127 – transport of SAAs, 141–145 – catabolic pathway, 118–120, Aminoacidopathies, 279–289 Ascorbic acid, 360, 361 125, 126 Aminoacidurias, 281, 182 Aspartate aminotransferase, 3, 5, 7 – glial metabolism, 122 Aminotransferase, 3, 5, 7, 10, 11, 13, 14 Astrocytes – nitrogen transfer, 118, 120, 122, Ammonia effects, 171 – aminotransferase isoform, 126 124, 126 Ammonia, 251–253, 255, 256 – energy metabolism in, 267 – transport in brain, 121, 125

# Springer-Verlag Berlin Heidelberg 2007 414 Index

Branched-chain aminotransferase Cold stress, 87 Disorders of glutathione metabolism (BCAT), 3, 4 Compartmentation, 3, 14 – g-glutamyl synthetase deficiency, – isoforms, 119 Control, ‘‘open loop’’, 64 279, 300 – localization in brain, 119 Corpus striatum, 64 – g-glutamyl transpeptidase – nitrogen shuttle in brain, 125 Creatine, synthesis, 106 deficiency, 279, 300 Branched-chain a-keto-acid Cysteine sulfinate decarboxylase – 5-oxoprolinase deficiency, – dehydrogenase – biosynthesis of taurine, 135 279, 300 complex, 120 – metabolism of L-cysteine, 135 – 5-oxoprolinuria (glutathione – maple syrup urine disease, Cysteine, 349 f synthetase deficiency), ‐ 120, 127 Cystine-glutamate (xc ) exchanger 279, 300 Breakfast, 86 – glutamate transport and, 144 Distribution taurine, 156–159 Calcium, 360, 368, 378 – GSH synthesis and, 145 Disulfide bonds, 370, 371 Canavan disease, 301, 311, 315–317, – interrelationship with glutamate DL-NAM, 75 335, 336 transporters, 144, 145 DOPA, 61, 72, 77–80, 82, 87 Cancer, 363, 364 – localisation, 144 , 60 f Carbamyl phosphate synthetase, – neurotoxicity and, 146 D-Serine 250, 251 – SAA transport and, 141 – biosynthesis and serine racemase, ‘‘Carbohydrate-craving’’, 85, 86 D-Aspartate 211, 212 Casein, 62 – biosynthesis, 217–219 – metabolism and transport, Catecholamine, 60–62, 70, 75, 79–81, – localization in the nervous and 212–214 84, 87, 88 endocrine system, 217 – neuromodulator and, 216, 217 Catecholaminergic transmission – metabolism, 219 – new roles, 215 – dopamine, 270, 271 – neurobiology, 217–220 – NMDA receptor dysfunction and, – , 270 – precursor for endogenous 215, 216 Cationic amino acid transporter (CAT), NMDA, 219 – regulation of NMDA receptors, 107, 108 – role of endogenous, 218 209–211, 214 Cell cycle, 350, 363 – transport and release, 218 – regulation of production, 212 Cell swelling, 155, 166–170 DDAH (Dimethylarginine – release, 209, 212, 214–216 Cell volume regulation, 160, 165, 167 dimethylaminohydrolase), 105 Endogenous neuroprotectants Cell-damaging-conditions, 163–165, Degeneration retina, 161, 181 – taurine, 271 175, 179 Depression, 68, 78, 86, 87 End-product inhibition, 79 Central nervous system, 25, 29, 31, 34, Derivatives taurine, 169, 182–184 Energy drinks, 182 35, 39, 40 Development, 157–159, 161, 167, Energy metabolism, 123 Cerebellar cell migration, 158 174–176, 184 Enzyme defects, 251, 252 Cerebellum, 352, 354, 356, 368, 373 Developmental disability, 283 Enzyme phosphorylation, 73 Cerebral palsy, 250, 251 Dextrin, 85 Enzymopathy, 251–257 Chemometabolism, 340 Dextrose, 85 Eosinophilia-myalgia syndrome Cholesterol, 61 Diet, high-carbohydrate vs (EMS), 69 , 75 high-protein, 86 Ephedrine, 88 Choline acetyltransferase, 253, 254 Dietary carbohydrates, 64, 78 , 177, 178, 183, 184 Choroid plexus, 60, 75 Dietary proteins, 62, 78, 85 Epinephrine, 60–62, 64, 79 Chronic fatigue syndrome, 378, 385 Dietary starches, 62 Essential amino acid, 184 Chronoarchitecture, 323, 340 Diffusion coefficient, 323, 331, 332 Estrogen, 61 Chronometabolism, 340 Dihydroxyphenylacetic acid Ethanol, 170, 171, 180, 182 a-chymotrypsin, 73 (DOPAC), 88 Excitotoxicity Cingulate cortex, 80 Diseases – glutamate receptors and, 146 Citrulline – Alzheimer (AD), 101, 104, 107 – SAA induced, 146 – concentration in brain and CSF,101 – multiple sclerosis, 102 Facilitated diffusion, 74, 75 – generation within proteins, 105 Disorders of GABA metabolism ‘‘False ’’, 78 – immunohistochemistry, 101 – GABA-transaminase deficiency, Fatty acids, 64, 75 – intermediate in citrulline-NO 279, 301 Fick’s law, 331, 332 cycle, 105 – pyridoxine dependency, Free radicals, 359, 360, 364, 370, 378, Citrullinemia, 109, 251, 256, 257 279, 300 381, 382, 384 Citrulline-NO cycle, 101, 103–106, – succinic semialdehyde Fumarate, 70 108, 109 dehydrogenase deficiency, Functional magnetic resonance Clozapine, 88 279, 301 imaging, 323–325, 332–334 Index 415

GABA, 252, 253 Glutamyl-L-cysteinyl , 349 Hyperammonemic brain edema – branched chain aminotransferase, Glutathione peroxidase, 350, 352, 359, – cerebral blood flow in, 270 118, 119, 121, 126 361, 378, 379 – glutamine in, 269, 270 – GABA aminotransferase Glutathione reductase, 359, 379 – organic osmolytes in, 269, 270 (GABA-T), 126 Glutathione S-, 350, 362 Hyperammonemic encephalopathies – GABA shunt, 5, 126 Glutathione synthetase, 350, 352 – animal models, 264 – metabolism, 126, 127 Glutathione, 350–370 – clinical characteristics in – SAA-induced release of, 141 Glycemic index, 62 humans, 263 GABA/glutamate-glutamine cycle, 4–9 Glycine receptors, 173–175, 177, Hypercapnia, 302, 329 GABAergic neurotransmission 179, 184 Hyperemia, 320, 324–326, 328, 329,

– GABAA receptor complex, 268 Glycine, 25 f 333–336, 338, 339 – peripheral benzodiazepine GSH Hyperglycemia, 64 receptors, 268 – g-glutamyl cycle and, 135, 138 Hypernatremia, 239–241 Gabapentin, 124 – g-glutamyltranspeptidase and, Hypoacetylaspartia, 311, 314, 317, GABA-T, 5, 10, 13, 14 138, 147 336, 337 GAD,4,5,13 – L-cysteine/L-cystine as precursors, Hypoargininemia, 109 Gamma-butyrolactone, 87 134, 135, 141 Hyponatremia, 226–228, 232, 236, 239 Gastric transit, 88 – non-excitatory neurotoxicity Hypothalamus, 48, 50–54, 83, 84, 87 therapy, 250, 257 and, 146 Identification of peptides Geometabolism, 340 Guanidino compounds, 100, 106, 109 – aggregation, 402 Gliotoxicity, 148, 149 Haber-Weiss reaction, 360 – Hplc, 402 Glucocorticoids, 68, 71 Haloperidol, 71, 87, 88 – immune tests, 404 Glutamate, 252 f Hemorrhagic shock, 80 – mass spectrometry, 402 , 4, 5, 13 High-carbohydrate vs high-protein, 86 – mixed disulfides, 403

Glutamate dehydrogenase, 3, 5, 7, 8 H2 receptor, 53 – non-covalent binding, 402 Glutamate receptor agonists, Histamine, 48, 50–54 – sequence, 402 179, 180 Histidase gene, 50–53 Immobilization stress, 80 Glutamate receptors, 165, 168, 169, decarboxylase, 50, 53 In vivo microdialysis, 87 171, 179 Histidinemia, 48, 51–54 Inborn errors of metabolism, 297 – AMPA, 139 Homeotherms, 307, 331 Indoleamine 2,3-dioxygenase (IDO), – excitotoxicity and, 146 Homocystinuria 67–69, 74 – mGluRs, 140, 141 – cobalamin C disease, 279, 295 INF-alpha, 69 – NMDA, 139, 140, 146 – cystathionine synthetase INF-gamma, 69 – SAAs and, 139, 140, 146 deficiency, 291–294 Inner ear, 354, 356, 357 family – hereditary folate malabsorption, Inositol phosphates, enhanced – localisation, 142 279, 295 production by SAAs, 140 – SAAs as substrates, 142, 143 – methionine synthase deficiency Insomnia, 69, 86 – subtypes of, 142 (Cobalamin E disease), , 62–64, 66, 71, 72, 76–78, 85, 86 Glutamate-glutamine cycle, 6, 8, 9 279, 295 Ischemia, 163–165, 167, 169, Glutaminase, 5, 6 – methylenetetrahydrofolate 178–180, 184 Glutamine synthetase, 3, 5, 7–10, 12, reductase deficiency, 279, 294 Isoleucine, 62, 64, 73, 76 118, 119, 123 – remethylation deficiency a-ketoglutarate dehydrogenase, effect Glutamine, 2–6, 10, 12–14, 251, 252, homocystinuria, 279, 294 of ammonia, 255 256, 257 Homovanillic acid (HVA), 78, 88 , 68, 69, 74 Glutaminergic neurotransmission Huntington’s disease, 332 – regulation of synthesis by – nitrosative stress, 268 Hydrogen peroxide, 350, 352, L-CSA, 145 – NMDA receptor activation, 267 359–361, 381 a-lactalbumin, 62 – NMDA receptor// 5-hydroxyindole acetic acid (5-HIAA), Large neutral amino acids (LNAA), 60, cGMP pathway, 263 78, 85, 86 64, 66, 76, 77, 85–88 g-glutamyl cycle 5-hydroxyindoleacetic acid, 254 LAT–1, 75 – astrocytes and, 135, 138 6-hydroxydopamine, 87 LAT1–4F2hc heterodimer, 75 – GSH synthesis and 135, 138 Hydroxyindole-O-methyltransferase Lateral tegmentum, 79 – L-cysteine and, 135 (HIOMT), 74 L-carnitine, 256 g-glutamylcysteine synthase, 138, 148 5-hydroxytryptophan (5-HTP), 61, 77, L-cysteic acid Glutamyl cysteine synthetase, 350, 354, 78, 87 – biosynthesis and metabolism, 135 361, 364 Hyperacetylaspartia, 311, 314 – interaction with excitatory Glutamyl transferase, 350, 363, 374 Hyperammonemia, 109, 171 receptors, 146 416 Index

– localisation in the brain, Liver transplantation, 256 NAAG peptidase, 308, 309, 317, 322, 135, 136 L-methionine, precursor for L-Hcys, 135 325–327, 332–337 – release, 139 Locus coeruleus, 79 NAAG synthase, 309, 326 – toxicity, 146 Long-lasting potentiation, 174 N-acetyl cysteine, 377, 382, 383 – transport, 143, 144 Long-term potentiation, 175, 370, N-acetylaspartylglutamate, 308, 309 L-cysteine 372, 378 Neurodegenerative diseases, 120, 357, – biosynthesis and metabolism, 135 L-serine, 25–35 378, 385 – GSH synthesis and, 135, 138, L-serine-O-sulphate Neuromodulator, 356, 357, 364, 141, 149 – alanine aminotransferase and, 148 365, 385 – interaction with excitatory – gliotoxicity, 148 , branched chain receptors, 146 ‘‘L-System’’, 75 aminotransferase isoform, 126 – localisation in the brain, 139 L-threonine, 39–41 Neuron codes, 329 – release, 139 Lysolecithin, 73 Neuron spikes, 328, 329, 331, 333, 335 – toxicity, 134, 146, 147 L-a-aminoadipate Neuroprotection, 180 – transport, 138, 142, 143, 145 – cystine-glutamate exchanger Neurosteroids, 253 L-cysteine sulphinic acid and, 144 Neurotoxicity – biosynthesis and metabolism, 135 – gliotoxicity, 148 – by SAAs, 146 – interaction with excitatory Macromolecule synthesis, 363, 364 – L-cysteine-induced, 147 receptors, 146 Magnetic resonance imaging – L-homocysteine-induced, 147, 148 – localisation in the brain, 135, 136 (MRI), 326 – protection against, 149 – release, 139 Magnetic resonance spectroscopy – S-methylcysteine-induced, 148 – toxicity, 146 (MRS), 309, 311, 323, 324, 337, 338 Neurotransmission, 358, 367, 371, 383 – transport, 140 Maple syrup urine disease (MSUD), Neurotransmitter L-cystine 120, 127 – acetylcholine, 75 – biosynthesis and metabolism, 135 – classical disease, 279, 289 – catecholamine, 60–62, 70, 75, 79, – GSH synthesis and, 135, 138, 141, – intermittent form, 279 80, 81, 84, 87, 88 145, 146 – thiamine responsive form, 279 – dopamine, 82, 85, 87, 88 – localisation in the brain, 135, 136, Medial prefrontal cortex, 60, 80, 82–88 – norepinephrine, 60–62, 70, 73, 141, 142, 145 , 60, 61, 63, 68, 74, 75 79, 80, 83–85, 87, 88 – release, 135, 138 Melphalan, 75 – serotonin, 60–64, 66, 68, 73–78, – toxicity, 146 Membrane potentials, 172 80, 82–87 – transport, 142, 143, 145 Memory, 365, 378, 381, 383 Learning and memory, 88, 365, Mental retardation, 250, 251, 256, 281, – branched-chain amino acids 378, 381 283, 286, 288, 290, 293–295, 298, and, 118 Leucine, 62, 64, 65, 73, 86 300, 301 – de novo glutamate synthesis, L-homocysteic acid Mesocortical tracts, 79, 80, 82, 87, 88 123–125 – interaction with excitatory Mesolimbic tracts, 79 – glutamate/glutamine cycle, 123 receptors, 146 Metabolism, 2, 3, 5–7, 9, 11–13 – glutamate/pyruvate cycle, 125 – localisation in the brain, 136 Metabotropic glutamate receptor, 307 Neurotransmitters, 158, 161, 162, 164, – release, 139 Methionine, 65, 73, 76 169, 176 – toxicity, 146, 148 a-methyldopa, 78 N-formylkynurenine, 66–68 – transport, 138, 140, 142–144 Microdialysis, in vivo, 87 a–7 nicotinic receptors, 68, 69 L-homocysteine Mitochondria, 3, 5, 14, 354, 357, 359, Nicotinamide adenine dinucleotide – biosynthesis, 135, 137 379, 381 (NAD), 68, 69 – neurotoxicity, 147–148 Mitochondrial oxidative metabolism, Nicotine withdrawal, 85, 86 – potentiation of b-amyloid 118, 119, 126 (NOS) toxicity, 147 Molecular water pump, 314, 317, 340 – inducible/induction, 101, 104,

– vitamin B12 and, 137, 148 Monoamine neurotransmitter, 74, 75, 105, 109 L-homocysteine sulphinic acid 77, 78 – neuronal, 101, 105 – biosynthesis and metabolism, 135 (MAO), 74, 254 Nitric oxide(NO), 100, 101, 103–110, – interaction with excitatory Multiple sclerosis, 310, 333 255, 360, 367 receptors, 141 Muscarinic cholinergic sites, 254 Nitrosoglutathione, 362, 367, 370 – localisation in the brain, 139 NAA dynamic model, 311–313, 338 NMDA receptors, 68, 252, 255 – release, 139 NAA synthase, 308, 311, 314, N-methyl-D-aspartate (NMDA) L-Homocystine, 135 326, 336 receptor, 358, 362, 365–367, Lipid peroxidation, 350, 360, 379, 381 NAAG peptidase inhibitors, 322 369–373 Index 417

Non-esterified fatty acids (NEFA), 64, – reverse phase Regulatory volume decrease, 228–231 66, 75, 76 chromatography, 404 Release Non-ketotic hyperglycinemia, 289–291 – UV detection, 404 – of SAAs, 141 Non-NMDA receptors, 365, 367, Peptides and behavior – SAA-mediated stimulation of, 141 372, 373 – growth control, 403, 406 Release taurine, depolarization, Noradrenaline, stimulation of – releasing factor, 403, 404 165, 169 release by SAAs, 141 Peptidylarginine deiminase (PAD), Re-polarization, 328–331, 333–336, Norepinephrine, 60, 62, 70–73, 79, 80, 101, 102, 105 338, 339 83–85, 87, 88 Peripheral-type benzodiazepine Reserpine, 87, 88 Norleucine, 73 receptors, 253 Retina degeneration, 161, 181 Obesity, 66, 86 Peroxynitrite, 360, 368, 382 Retina, 79, 80, 88, 180, 181, 183, 184, Olfactory bulb, 79 Pharmacology, 374–376 354, 356, 357, 373 ‘‘Open-loop’’ control, 64 Phenylacetate, 255, 256 , 310, 322, 332, 333, Ornithine, concentration in brain and Phenylalanine hydroxylase (PAH), 61, 383–385 CSF, 101 62, 72, 73 Seasonal affective disorder syndrome , (ODC), Phenylalanine, 60–63, 65, 69, 70, 72, 73, (SADS), 86 107, 109 79, 87, 88 Seizures, 177, 178, 183 Ornithine transcarbamylase (OTC), Phenylethylamine, 72 Sensors, ‘‘variable ratio’’, 82, 86 251–257 Phenylketonuria Serotonin N-acetyltransferase, 74 Osmolarity, 161 – defects of biopterin metabolism, Serotonin, 60 f Osmoregulation, 314, 237, 340 279, 280 Signal transduction, 364, 365, 385 Osmotic disequilibrium, 314, – phenylalanine hydroxylase Sleep, 64, 86 315, 340 deficiency, 285–287 S-methylcysteine, toxicity of, 148 Ovalbumin, 62 Phenylketonuria (PKU), 60 Sodium benzoate, 255, 256 Oxidation, 352, 360, 364, 371, 376, Phenylpropanolamine, 88 Sparse-fur mouse (spf mouse), 252, 379–381 Phenylpyruvic acid, 72 255, 257 Oxidative stress, 352, 353, 355, 358–362, Phophate activated glutaminase, 6, 12 Spinal cord, 352, 354, 356, 357, 373, 364, 368, 379–382, 385 Phosphorylation, 73, 77, 79, 80 382, 383 – Cystine-glutamate exchanger p-hydroxyphenylpyruvate, 70 Splanchnic system, 63 and, 146 Pineal gland, 60 S-sulpho-L-cysteine Pain, 69, 86 Plasma ratio, 76, 77, 82, 86 – stimulation of excitatory Parkinson’s disease, 78, 84, 87, 88, 357, Poikilotherms, 307, 330 receptors by, 135, 138 365, 380 Portal vascular system, 72 – stimulation of noradrenaline ‘‘Peak E’’, 69 Potassium stimulation, 167, 168 release by, 141 Peptide formation 14–3–3 protein, 77, 78 Substantia nigra, 354, 356, 357 – g- pseudopeptide bond, 403 Premenstrual syndrome, 85, 86 Sucrose, 62, 85 – b-aspartyl transfer, 403 , 107, 109 Superoxide dismutase (SOD), 69, 359, – g-glutamyl transfer, 403 Pyruvate carboxylase 360, 361, 379, 380, 382 – peptidase effect on – anaplerosis, 124 Superoxide radical, 359 proteins, 403 – glutamate/pyruvate cycle, Swelling, 227–238, 242, 243 – phosphate activation and direct 123, 124 Sympathetic nervous system, 79–81, synthesis, 403 Pyruvate carboxylase, 7, 8, 11, 12 83, 84 Peptide function Pyruvate recycling, 6–8 Synapses, 80, 84, 87 – co-transmitter, 402 Quinolinic acid, 68, 255 Synaptosomes, 72, 75 – growth control, 403, 406 Raphe nuclei, 82 System L transport, 49 – hormesis, 403 Receptors g-aminobutyrate, 172, 173 System N transport, 49 – neuro-modulator, 403, 404 Receptors glutamate, 165, 168, 169, System y+ – transmitter, 403, 405 171, 179 – induction, 107 – transport-regulator, 406 Receptors glycine, 173–175, 177, Taurine, 156 f Peptide purification 179, 184 – biosynthesis, 159, 184 – gel filtration, 404 Receptors taurine, 172, 175, 176 – derivatives, 169, 182–184 – hydrolysis and ninhydrin Receptors, 358 f – distribution, 156–159 coloring, 404 Reduction, 350, 352, 354, 357, 359–364, – receptors, 172, 175, 176 – ion exchange, 404 370, 379, 382, 384 TCA cycle, 2–11, 14 – normal phase Refractive period, 328, 330, 340 Testosterone, 61

chromatography, 404 Regulation cell volume, 160, 165, 167 Tetrahydrobiopterin (BH4), 72, 77, 79 418 Index

Thermogenesis, 88 Tryptophan dioxygenase (TDO), 62, – citrullinemia, 279, 298 Thermoregulation, 176, 177 66–70 – hyperammonemia, Thimerosal, 149 1 (TPH1), 61, hyperornithinemia, Thiol, 349, 360, 363–366, 368–371, 72, 77, 79 homocitrullinuria syndrome, 373, 376, 379 Tryptophan hydroxylase 2 (TPH2), 77, 279, 298 Thyroid gland, 61 78, 87 – lysinuric protein intolerance, 279, TNF-alpha, 69 Tryptophan pyrrolase, 68 298, 299 Tocopherol, 360, 361, 379, 382 Tryptophan, 60 f – N-acetylglutamate synthetase Transpeptidase, 352 Tuberohypophyseal neurons, 79 deficiency, 279, 297 Transport, 2, 3, 8, 9 Tuberomamillary neurons, 51 – ornithine transcarbamylase – ASC transporter, 141–143 aminotransferase (TAT), 62, deficiency, 279, 297, 298 – cystine-glutamate exchanger, 141, 68, 70–72 Urokanic acid, 50 142, 144, 145 (TH), 72, 80 Valine, 60, 62, 64, 65, 70, 73, 87 – glutamate transporter family, Tyrosine, 79–83 ‘‘Variable ratio sensors’’, 82, 86

142, 143 Tyrosinemia, 71 Vitamin B12, L-Hcys and, 148 – into astrocytes, 142, 144, 145 Urea cycle, 251–257 Wedensky inhibition, 329, 331, 332 – of SAAs, 141–145 – extramitochondrial , 103 Wedge preparation, 374, 376 - Transport mechanisms, 349 Urea cycle defects XAG transporters, See glutamate Transporter taurine, taurine uptake, – arginase deficiency, 279, 298 transporter family 160–162, 170, 175, 181, 184 – argininosuccinic aciduria, , 68 ‐ Tricarboxylic acid cycle (TCA cycle) 279, 298 Xc exchanger, See cystine-glutamate – a-ketoglutarate, 120 – carbamyl phosphate synthetase exchanger Tripeptide, 349, 364, 366 deficiency, 279, 297 Xenobiotics, 350, 362, 363, 379