CONTRffiUTORS. GRISOLIA, S. Instituto de Investigaciones Cito16gicas de la F.I.B Valencia Spain

Transcription

1 CONTRffiUTORS ARMSTRONG, D. BASILE, A. S. liver Disease Section and Laboratory of Neuroscience Bethesda, MD U.SA. CARDA, P. Dto. Cirugia General y Digestiva Hospital Ram6n y Cajal Madrid COOPER, A. J. L. Dept. Biochemistry and Neurology Cornell University Medical College New York, NY U.SA. COSTA, E. U.SA. FELIPO, V. Cito16gicas de la F.I.B. GRISOLIA, S. Cito16gicas de la F.I.B. GRAU, E. Citologicas de la F.I.B GUIDOTTI, A. U.SA HAWKINS, R. A. Dept. Physiology and Biophysics University of Health Sciences Chicago Medical School North Chicago, IL U.SA HERRERO, I. Dept. Bioquimica Facultad de Veterinaria Universidad Complutense Madrid JONES, E. A. Liver Diseases Section and Laboratory of Neurosciences Bethesda, Maryland U.SA 143

2 KHARMALOV, A. KIEDROWSKI, L. Fidia -Georgetown Institute lajtha, A. Nathan S. Kline Institute for Psychiatric Research Center for Neurochemistry Orangeburg, NY MANS, A. M. Dept. Physiology and Biophysics University of Health Sciences Chicago Medical School North Chicago, IL MICHAELIS, E. Dept. Pharmacology and Toxicology Center for Neurobiology and Immunology Research University of Kansas Lawrence, KS MIRAS-PORTUGAL, M. T. Dept. Bioquimica Facultad de Veterinaria Universidad Complutense Madrid MINANA, M. D. Cito16gicas de la F.I.B. MOREJON, E. Unidad de Nutrici6n Clinica y Dietetica Hospital Ram6n y Cajal Madrid RAABE, W. Depts. Neurology and Physiology V. A. Medical Center University of Minnesota Minneapolis, MN RODES, J. Hospital Clinic i Provincial Unidad de Hepatologia Facultad de Medicina Universidad de Barcelona Barcelona SANCHEZ-PRIETO, J. Dept. Bioquimica Facultad de Veterinaria Universidad Complutense Madrid SASTRE, A. Unidad de Nutricion Clinica y Dietetica Hospital Ram6n y Cajal Madrid. SKOLNICH, P. Liver Diseases Section and Laboratory of Neuroscience Bethesda, MD U. S. A. WROBLEWSKI, J. T. Fidia -Georgetown Institute YURDAYDlN, C. Liver Diseases Section and Laboratory of Neuroscience Bethesda, MD

3 INDEX Acetylglutamate efflux from mitochondria, 5 in hyperammonemia, 4, 6 in the regulation of urea cycle, 2 levels in protein deprivation, 5 synthesis in hyperammonemia, 4 Acidosis and ammonia excretion, 30 ACPD,101 Adenylate kinase, 25 Adenylosuccinate lyase, 25 Adenylosuccinate synthetase, 25 B-alanine, 74 Albumin,48 Alcohol consumption, 45 4-aminopyridine, 96 Aminotransferases role in nitrogen homeostasis, 26 Ammonia activation of the NMDA receptor, 87 and Ct- extrusion, 75 ' and IPSP, 72 and ph;, 78 and proteolysis of MAP-2, 86 detoxification, 1 effects on Em;p, 73 enzymes involved in production of, 24 enzymes involved in removal of, 22 in liver cirrhosis, 48 Ammonia metabolism, 14,21 in acidosis, 30 in brain, 29 in gut, 30 in kidney, 30 in liver, 30 in muscle, 27 Ammonia physical properties, 21 Ammonia toxicity, 1, 14,89 molecular mechanism, 89 role of NMDA receptor in, 89 AMP deaminase, 25 Animal models of hepatic encephalopathy, 60, 84 benzodiazepine ligands in, 59 effect of flumazenil on, 62 Anorexia, 45 Arachidonic acid and glutamate release, 99 and protein kinase C, 100 Aromatic amino acids, 51 Aspartate aminotransferase, 29 Asterixis, 40 Benzodiazepine agonists, 58 Benzodiazepine inverse agonists, 61 Benzodiazepine antagonists, 61 Benzodiazepine ligands, 57 in brain, 60 in diagnosis of hepatic encephalopathy, 67 in human cirrhosis, 61 in liver failure, 61 in models of hepatic encephalopathy, 60 in therapy of hepatic encephalopathy, 61 role in hepatic encephalopathy, 57 Benzodiazepine receptor subtypes, 57 Brain dysfunction, 13 Brain glucose consumption, 14 Brain protein breakdown, 110 Brain protein synthesis, 108 Branched-chain amino acids, 27, 51 Bumetanide, 76 Ca2 and glutamate release, 96 homeostasis, 131 in ammonia toxicity, 89 in neurons, 131 in synaptic signal transduction, 131 Calpain and life span, 107 and proteolysis of MAP-2, 86 and proteolysis of PKC, 98 effect of camitine on, 114 in aging brain, 112 in brain regions, 112 stimulation by isovalery1carnitine, 114 substrate specificity, 112 Carbamylglutamate activator of carbamylphosphate synthetase, 9 in the treatment of hyperammonemia, 9, 43 Carbamylphosphate synthetase, 2, 4,

4 Carbamylphosphate synthetase (Cont.) in hyperammonemia, 3 in protein deprivation, 4 Camitine and calpain, 114 Cathepsin D in aging brain, 111 Cirrhotic patients loss of muscular mass, 45 malabsorption, 46 nutritional state, 45 vitamins in, 49 Cr,71 cr -ATPase, 76 cr -extrusion, 75 Co+ 2, 74 Cu+ 2, 74 Depolarization, 71, 96 Diacylglycerol, 97, 101 Diagnosis of hepatic encephalopathy, 41 Diazepam, 60 Diet, 42, 50 Dietary protein, 5, 50 E cl,72 ~C03' 73 ~,72 Ethacrynic acid, 76 Exocytosis, 95 Fe+ 2, 74 Flumazenil, 58 effect on human hepatic encephalopathy, 42, 62 effect on models of hepatic encephalopathy, 64 Fluoroacetate, 74 Free fatty acid, 100 Fulminant hepatic failure, 57 Furosemide, 76 GABA, 57,72 GABA A receptor complex, 57 Galactosamine, 58 Gangliosides, 135 and [Ca 2 +]i, 135 and calmodulin, 138 and glutamate neurotoxicity, 135 and protein kinase C translocation, 136, 139 bioavailability, 136 Glasgow coma scale, 40 Glutamate binding protein, 121, 125 antibody, 121, 124 Glutamate carrier, 96 Glutamate dehydrogenase relative activity in various organs, 24 role in ammonia metabolism, 22 Glutamate ionotropic receptors, 120, 133 dynamic state, 133 polymorphism, 133 structural variability, 131, 134 subtypes, 120 Glutamate metabotropic receptors, 134 Glutamate release, 95 arachidonic acid and, 99 energy requirements, 96 protein kinase C and, 96 Glutamate toxicity, 135 in CNS pathology, 135 protection by lysogangliosides, 135 therapeutic approaches, 136 Glutaminase inhibition, 16 Glutaminase K properties, 24 Glutaminase L, properties, 24 location in the liver, 24 Glutamine as a metabolic fuel for gut, 30 as a non toxic carrier of ammonia, 32 as a source of urea nitrogen, 31 central role in nitrogen homeostasis, 23 in acidosis, 30 Glutamine synthesis, 7, 14, 48 Glutamine synthetase and ammonia concentration, 8 in protein deprivation, 8 relative activity in various organs, 22 role in ammonia removal, 22 Glutamine transaminase K, 26 as a source of ammonia, 27 identity with cysteine-s-conjugate-b-lyase, 26 Glutamine transaminase L, 26 Glycine, 74 Glycine cleavage system, 26 importance in the kidney, 26 GM1,129 Gut ammonia formation from, 30 H+, 74 HC0 3 -,77 Hepatic coma, 13 Hepatic encephalopathy, 57 acute and chronic, 39 asterixis, 40 clinical manifestations, 39 clinical stages, 40 diagnosis, 41 electroencephalogram in, 41 GABA A receptor in, 57 hyperammonemia in, 83 pathogenesis,

5 Hepatic encephalopathy (Continued) role of benzodiazepine ligands in, 59 symptoms, 39 therapy, 42 treatment with flumazenil, 62 types of, 39 Hepatic failure, 45 nutritional considerations, 45 Hepatocerebral degeneration, 39 Histidine, 74 Hyperammonemia, 71 and acetylglutamate, 3, 6 and hepatic encephalopathy, 78, 83 and urea cycle, 2 animal models, 2, 84 effects on MAP-2, 86 effects on microtubules, 84 treatment with carbamylglutamate, 9 Hyperglycemia, 47 Hypoglycemia, 46, 74 Immediate early genes, 133 Inositol triphosphate, 101 Interorgan flux of nitrogen, 27 Ionotropic receptors, 120, 133 IPSP,72 Isovalerylcamitine, 113 K+, 72, 75 K+ channels, inactivation by PKC, 99 K+/CI--cotransport, 75 Lactitol, 42 Lactuiose, 42 Leucine, 74 Ufe span, 107 LIGA derivatives, 136 Upid metabolism in cirrhosis, 47 Uver failure, 13 Uver, role in amino acid degradation, 30 Long term potentiation, 102, 119 Lysine, 74 Lysogangliosides, 136 as therapeutic agents, 137 in experimental brain ischemia, 138 in vivo activity, 137 MAP-2 NMDA receptor and, 87 phosphorylation, 86 proteolysis, 86 Metabolic compartmentation in the brain, 29 in the liver, 30 Metabotropic receptors, 101, 134 presynaptic, 101 Methionine sulphoximine, 14 Microtubules in hyperammonemia, 84 Minerals in liver cirrhosis, 49 MK-801, prevention of ammonia toxicity, 90 Muscle, role in catabolism of branched-chain amino acids, 27 as a source of glutamine and alanine, 28 Neurotransmitter release, 95, 129 Neutral amino acids, 16 NH/, see ammonia NMDAR1,123 NMDAR2,123 NMDA receptors 87, 99, 119 cloning of cdna, 123 families, 119 heterogeneity, 121, 123 in ammonia toxicity, 89 in neuronal development, 119 in neurodegeneration, 119 isolation, 121 ligand binding sites, 119 physiological function, 119 subunits, 121 Number connection test, 41 Nutrition in liver cirrhosis, 45 Periportal hepatocytes, 24, 31 Perivenous hepatocytes, 31 Plasma membrane potential, 96 Portacaval shunt, 13 Portosystemic encephalopathy index, 41 Proteases in aging, 111 Protein breakdown, 107 alterations, 111 during development, 111 in malnutrition, 108 Protein deprivation, 5 and acetylglutamate, 7 and blood ammonia, 6 and carbamylphosphate synthetase, 3 and glutamine synthetase, 7 and urea cycle, 5 in liver cirrhosis, 50 Protein-free diet, 5 Protein kinase C, 96 activation of, 97 and K+ channels, 99 in glutamate release, 98 translocation, 136 Protein kinase M, 98 Protein metabolism in cirrhosis,

6 Protein synthesis, 108 during development, 110 Protein turnover, 108 effect of temperature, 113 in cirrhosis, 48 Purine nucleotide cicle relative importance in different tissues, 25 role in ammonia formation, 25 Receptor abuse dependent antagonism, 136 Serine hydroxymethyltransferase, 25 importance in the kidney, 25 Symptoms of hepatic encephalopathy, 39 Synaptic signal transduction and DNA transcription, 132 immediate early genes, 133 third nuclear messengers, 132 Synaptic transmission, 129 Synaptosomes, 95 Transdeamination, 25 Transreamination, 25 Transmitter release, 129 Treatment of hepatic encephalopathy, 42, 52 benzodiazepine receptor ligands, 61 carbamylglutamate, 9, 43 diet in, 42, 50, 52 flumazenil, 42, 62 Treatment of hepatic encephalopathy (Cont.) lactitol, 42 lactulose, 42 nutritional considerations, 45 Tryptophan transport, 14 Tubulin effect of hyperammonemia on, 84 proteolysis, 110 synthesis, 84 Urea cycle acetylglutamate in the regulation of, 2 effects of hyperammonemia on, 3 effects of protein deprivation on, 5 in cirrhosis, 2, 48 possible role in acid-base balance, 31 regulation, 1, 32 response to dietary protein, 2, 5 role in the removal of waste nitrogen, 31 Urea excretion in hyperammonemia, 2 in protein deprivation, 5 stimulation by carbamylglutamate, 9 Vesicular release, 95 Vitamins, in cirrhosis, 49 Zinc,