Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cross-sectional study was performed to define patients at risk of developing liver disease due to long-term treatment with anticonvulsive drugs. The activities of gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase and the concentrations of primidone, phenobarbital, phenytoin, and valproic acid in serum were estimated. Epileptic children before therapy were used as controls. The results indicated enzyme induction due to phenobarbital and both enzyme induction and liver cell damage or plasma membrane leakage due to phenytoin. Gamma-glutamyltransferase may be an early indicator of liver disease due to valproic acid.
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PMID:Effects of anticonvulsive drugs on the activity of gammaglutamyltransferase and aminotransferases in serum. 287 3

We measured neurotransmitter markers in autopsied brain of infants with glycine encephalopathy (GE). Because patients with GE develop intractable seizures, special attention was devoted to those neurotransmitter systems implicated in human epilepsy. Mean levels of glycine in the frontal cortex of GE patients were three times higher than control values. No abnormalities were observed for concentrations of gamma-aminobutyric acid (and related receptors), other major neurotransmitter amino compounds, or activities of cholineacetyltransferase and aspartate aminotransferase. Mean acetylcholinesterase activity was significantly elevated by 46%. As experimental data suggest, glycine markedly potentiates the action of the excitatory neurotransmitter glutamic acid. To the extent that the brain seizures in patients with GE can be explained by this mechanism, pharmacotherapy with excitatory amino acid antagonists may represent a new approach to the treatment of GE.
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PMID:Brain neurotransmitters in glycine encephalopathy. 290 30

Serum amino acid (AA) profiles are altered in epilepsy. It is not clear whether this is due to the disease process itself or to other variables such as seizure type, seizure frequency, duration of illness, medication, or altered liver function. We investigated serum AA profiles and liver enzymes in 73 epileptic patients and 90 healthy subjects and evaluated the data by analysis of variance to discriminate between age, sex, seizure type, duration of illness, seizure frequency, antiepileptic drug (AED) and increased serum liver enzyme levels, and their putative interaction with the serum AA profile. There was no correlation between the changes in the AA profile and age, duration of illness, seizure frequency, and seizure type. Seventy-two percent of the AED-treated patients and 33% of the unmedicated patients showed an increase in one or several serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma-glutamyl transferase (gamma-GT)]; particularly gamma-GT. We observed a significant increase in serum concentrations of glutamine and glycine and decreased levels of taurine, threonine, serine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, and arginine in AED-treated patients but not in unmedicated patients. These results show that the changes in the serum AA profiles of epileptic patients treated with AEDs occur in patients with alteration of serum liver enzymes; whether this implies a causal relation is still uncertain.
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PMID:Serum amino acids, liver status, and antiepileptic drug therapy in epilepsy. 809 92

Gabapentin is a novel anticonvulsant drug. The anticonvulsant mechanism of gabapentin is not known. Based on the amino acid structure of gabapentin we explored its possible effects on glutamate and gamma-aminobutyric acid (GABA) metabolism in brain as they may relate to its anticonvulsant mechanisms of action. Gabapentin was tested for its effects on seven enzymes in the metabolic pathways of these two neurotransmitters: alanine aminotransferase (AL-T), aspartate aminotransferase (AS-T), GABA aminotransferase (GABA-T), branched-chain amino acid aminotransferase (BCAA-T), glutamine synthetase (Gln-S), glutaminase (GLNase), and glutamate dehydrogenase (GDH). In the presence of 10 mM gabapentin, only GABA-T, BCAA-T, and GDH activities were affected by this drug. Inhibition of GABA-T by gabapentin was weak (33%). The Ki values for inhibition of cytosolic and mitochondrial forms of GABA-T (17-20 mM) were much higher than the Km values for GABA (1.5-1.9 mM). It is, therefore, unlikely that inhibition of GABA-T by gabapentin is clinically relevant. As with leucine, gabapentin stimulated GDH activity. The GDH activity in rat brain synaptosomes was activated 6-fold and 3.4-fold, respectively, at saturating concentrations (10 mM) of leucine and gabapentin. The half-maximal stimulation by gabapentin was observed at approximately 1.5 mM. Gabapentin is not a substrate of BCAA-T, but it exhibited a potent competitive inhibition of both cytosolic and mitochondrial forms of brain BCAA-T. Inhibition of BCAA-T by this drug was reversible. The Ki values (0.8-1.4 mM) for inhibition of transamination by gabapentin were close to the apparent Km values for the branched-chain amino acids (BCAA) L-leucine, L-isoleucine, and L-valine (0.6-1.2 mM), suggesting that gabapentin may significantly reduce synthesis of glutamate from BCAA in brain by acting on BCAA-T.
Epilepsy Res 1995 Sep
PMID:Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. 856 62

In a prospective study 50 children with new onset epilepsy were investigated. Routine screening for complete blood count, serum protein, albumin, gamma-glutamyltransferase (gamma-GT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and coagulation studies before, 3, 6 and 9 weeks after commencement of antiepileptic therapy with valproate were carried out. Serum B12 and folate levels were also determined in 29 patients. The aim of the study was to evaluate the effect of VPA on these laboratory findings. We found a significant reduction of red blood count and platelet count, whereas MCV showed a significant upward trend. Vitamin B12 levels were elevated after starting VPA therapy. We found no elevations of liver enzymes, but a significant transient reduction of ALT after 3 and 6 weeks and significantly reduced serum protein and albumin after 3, 6 and 9 weeks. Coagulation studies revealed a significant downward trend in serum fibrinogen and upward trend in thrombin time. The other parameters showed no significant changes after onset of VPA treatment. We think that reduced red blood cell and platelet counts, and elevated MCV indicate a direct toxic effect on a hematopoietic precursor or stem cell in patients treated with VPA. Furthermore, reduced protein, albumin and fibrinogen indicate an impaired liver synthetic function in asymptomatic children treated with VPA monotherapy.
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PMID:Hematologic manifestations and impaired liver synthetic function during valproate monotherapy. 873 99

Patients with epilepsy on long term antiepileptic drug (AED) therapy deserve special consideration not only concerning seizure control but also the effect on anaesthetic metabolism and hepatorenal functions. In the present study, we examined the effects of sevoflurane anaesthesia on plasma inorganic fluoride (F-) level and hepatorenal function in patients with and without AED therapy. Twenty-two patients (12 with AEDs = AED group, and ten without AEDs = control group = C group), ASA I, who were free of hepatorenal disease, received approximately 2-3 h sevoflurane anaesthesia. Plasma F- analysis was performed at the stages of: 1) induction of anaesthesia, 2) conclusion of anaesthesia, 3) 15 h after the conclusion of anaesthesia, using an ion-selective electrode calibrated with a standard solution of sodium fluoride. Pre- and postoperative hepatic (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin) and renal (blood urea nitrogen, creatinine) function was tested. There were no significant differences between the two groups in the average age (AED group = 9.4 and control group = 10.1 y.o.), body weight, duration of anesthesia, and MAC hours (2.6 and 2.4). The mean peak F- levels were 15.5 and 13.6 microM, in AED and C groups (not significant), respectively. No patient exhibited F- values greater than 50 microM, the hypothetical nephrotoxic threshold. The patients showed no abnormal values either in hepatic or renal function tests postoperatively. These results suggest approximately 2-3 h sevoflurane anaesthesia to be safe in patients taking AEDs.
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PMID:Clinical characteristics and biotransformation of sevoflurane in paediatric patients during antiepileptic drug therapy. 888 Aug 18

We assessed the effects of sodium valproate and carbamazepine monotherapy on bone mineral density (BMD) in children. BMD at the lumbar vertebrae (L1-L4) and radius-ulna was measured by the dual-energy x-ray absorptiometry (DEXA) method in 19 children (9 girls, 10 boys) with uncomplicated epilepsy and in 57 healthy children (28 girls, 29 boys), between the ages of 6 and 12 years. The study patients had been receiving either sodium valproate (n = 13) or carbamazepine (n = 6) monotherapy for more than 6 months. There were no significant differences between the control and study patients in age, height, weight, physical activity, or of serum concentrations of calcium, phosphate, and transaminases (aspartate aminotransferase, alanine aminotransferase). However, the serum alkaline phosphatase concentration was greater in the patient group as compared with the control group. BMD values were lower in girl patients (L1-L4; 0.497 +/- 0.08 vs 0.566 +/- 0.07 g/cm2, p < 0.05), but not in boys (0.534 +/- 0.06 vs 0.530 +/- 0.08 g/cm2). While BMD reduction was 8% in valproate therapy (midregion of radius-ulna; 0.287 +/- 0.03 vs 0.312 +/- 0.04 g/cm2, p < 0.04), it was reduced only 4.5% in the carbamazepine-treated group (0.298 +/- 0.01 vs 0.312 +/- 0.04 g/cm2, statistically not significant), although the mean durations of monotherapy with valproate (1.8 +/- 0.7 years) and carbamazepine (1.7 +/- 0.8 years) were similar. Thus decreased bone mineralization was observed in children with epilepsy, treated with sodium valproate even though treatment was for a rather short time.
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PMID:Effect of antiepileptic drugs on bone mineral density in children between ages 6 and 12 years. 1004 42

Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degradation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.
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PMID:Neuroactive amino acids in focally epileptic human brain: a review. 1055 79

We investigated whether a combination of risk factors affects the free phenytoin (PHT) fraction by multiple regression analyses in 30 patients with severe motor and intellectual disabilities (SMID) with epilepsy. The risk factors analyzed were gender, age, total PHT concentration, albumin concentration, aspartate aminotransferase, alanin aminotransferase, serum creatinine, blood urea nitrogen, and antiepileptic drug concentrations. Serum levels of total and free PHT were measured by fluorescence polarization immunoassay. Free PHT fractions were between 7.2% and 17.3% (average 10.9%). Two factors, hypoalbuminemia and valproate (VPA) coadministratation with PHT, increased free PHT fraction, and a combination of these two markedly increased free PHT fraction. Patients with these double risk factors have a high risk of exceeding the therapeutic range of serum-free PHT concentration even if their total PHT concentration does not. Therefore, we should monitor free PHT concentration, especially in SMID patients with epilepsy, because they may have hypoalbuminemia and are treated with antiepileptic drug polytherapy and, moreover, cannot report adverse effects of the drugs.
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PMID:Synergistic effect of valproate coadministration and hypoalbuminemia on the serum-free phenytoin concentration in patients with severe motor and intellectual disabilities. 1215 11

The authors present a case of a patient treated with valproic acid for seizure disorder who presented with acute mental status changes consistent with encephalopathy. Notably, her serum ammonia level was 3 times the upper limit of normal, despite an only mildly elevated aspartate aminotransferase and normal bilirubin. Her serum valproic acid level was in the therapeutic range. Her symptoms resolved with discontinuation of valproic acid and supportive care. The authors review the possible mechanisms of valproic acid-associated hyperammonemia with encephalopathy and propose clinical practice modifications to minimize the incidence of this adverse reaction to this generally well-tolerated and clinically important psychotropic medication.
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PMID:Valproic acid-induced hyperammonemia: a case report. 1534 8


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