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PubMed1988

Organization of GABA and GABA-transaminase containing neurons in the gustatory zone of the nucleus of the solitary tract.

Previous cytoarchitectural and electron micrographic studies have indicated that the gustatory zone of the nucleus of the solitary tract (NST) may contain local circuit neurons. It is known that neurons of the caudal "visceroceptive" NST contain GABA, glutamic acid decarboxylase (EC 4.1.1.15), and GABA-transaminase (GABA-T; 4-aminobutyrate: 2-oxoglutarate aminotransferase; EC 2.6.1.19). The present study was conducted to determine whether or not neurons in the gustatory zone of the NST of rat contain GABA and the principle degradative enzyme of GABA, GABA-T. Transganglionic transport of horseradish peroxidase (HRP) was used to identify chorda tympani (CT) nerve terminal fields. Immunohistochemical studies were combined with transport experiments to evaluate the organization of GABA immunoreactive neurons in CT terminal fields. Results show that GABA immunoreactive neurons and puncta are located within CT terminal fields. These neurons evince small ovoid morphologies resembling Golgi interneurons, and comprise an average of 18% of total neurons in CT terminal fields. Independent histochemical studies reveal that approximately 82% of GABA immunoreactive neurons within CT terminal fields exhibit GABA-T activity. Retrograde transport of HRP was used in additional studies to evaluate whether or not axons of putative GABAergic neurons project to the second-order central gustatory relay located in the caudal parabrachial nucleus (PBNc), to the caudal NST, or to regions surrounding the rostral or caudal NST. Combined studies indicate that GABA immunoreactive neurons in the gustatory NST do not project axons to the PBNc, to the caudal NST, or to regions adjacent to the rostral or caudal NST.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗
PubMed1983

Cloning the Escherichia coli K-12 argD gene specifying acetylornithine delta-transaminase.

The argD gene of Escherichia coli was shown to be present in plasmids pLC2-28 and pLC3-11 of the collection of Clarke and Carbon [Cell 9 (1976) 91-99]. The gene was cloned into pBR322 as a 6.3-kb BamHI fragment. Enzyme determination showed that the cloned DNA contains the structural gene for acetylornithine delta-transaminase. The argD DNA was used as a probe in hybridization experiments which indicated that the argM gene resides in a duplicated portion of E. coli DNA that is highly similar to the argD region.

Arginine↗
PubMed1987

Agarose gel electrophoresis of human erythrocyte glutamic-pyruvic transaminase (GPT EC 2.6.1.2).

The method of choice to determine erythrocyte glutamate-pyruvic transaminase (GPT) including rare variants was starch gel electrophoresis. Methods using agarose as gel medium were not reported to our knowledge. We present an adapted method using the Tris/maleate buffer system and an agarose of low endosmosis. The common as well as rare variant types of GPT were quickly and reliably separated. In addition, a method for the consecutive determination of esterase D (ESD) and GPT on the same gel using the malic acid buffer system is described.

Alanine Transaminase↗
PubMed1989

Development of homospecific activity of GABA-transaminase in the mouse cerebral cortex and cerebellum and in neurons cultured from these brain areas.

The homospecific activity of GABA-transaminase (EC 2.6.1.19; GABA-T) in brain or neurons was determined as a function of development in vivo or in culture by measuring the enzyme activity together with the relative amount of GABA-T apoenzyme by the aid of a monospecific anti-GABA-T antibody. It was observed that both in cerebral cortex and cerebellum in vivo and in neurons cultured from these brain regions the homospecific activity of GABA-T changed during development. By incubation of tissue extracts with similar extracts in which GABA-T activity had been selectively and irreversibly destroyed with gamma-vinyl GABA (Vigabatrin) it was established that this change in homospecific activity was at least partly due to the presence of an endogenous activator of GABA-T. The results point towards a rather complex endogenous regulation of GABA-T during development in vivo and in vitro.

4-Aminobutyrate Transaminase↗
PubMed1987

Serum transaminases activity and histopathological changes in Clarias lazera chronically exposed to nitrite.

Increase in serum transaminases (GOT and GPT) activity attributable to nitrite toxicity was observed in juvenile Clarias lazera after chronic exposure to nitrite. The application of SGOT and SGPT assays for monitoring the effect of nitrite exposure over a 6-month period has shown that changes in activities are correlated with histological effects in Clarias liver. Kidneys from fish exposed to nitrite were not noticeably different histologically from that of control fish. Hypertrophy and hyperplasia were the most consistent lesions that occurred in the gills. Lifting of lamellar epithelium and necrosis of some epithelial cells were also prominent.

Alanine Transaminase↗
PubMed1993

Platelet GABA-transaminase in epileptic children: influence of epilepsy and anticonvulsants.

The relationship between platelet GABA-transaminase (GABA-T) activity and either epilepsy or its treatment has been studied in 281 epileptic children: 55 were newly diagnosed untreated patients and 226 were chronically receiving anticonvulsants (154 in monotherapy and 72 in polytherapy). Results were compared with those from 48 control children. Untreated children had a GABA-T activity of 9.1 +/- 3.7 pmol/min/mg protein, lower than the control group (10.6 +/- 3.8 pmol/min/mg, P < 0.05), whereas treated epileptic children had higher values (11.9 +/- 6.3 pmol/min/mg) than those untreated (P < 0.01). In untreated children, the seven with absences and the nine with simple partial seizures had a GABA-T activity of 6.9 +/- 3.3 and 7.8 +/- 3.2 pmol/min/mg, respectively, lower than the control group (P < 0.05). In treated patients, those receiving valproate (VPA) in monotherapy had a GABA-T activity of 15.3 +/- 7.5 pmol/min/mg, higher than both the control group and the untreated children (P < 0.001). All patients receiving VPA in mono- or polytherapy had a higher activity than those receiving other anticonvulsants (16.4 +/- 8.4 vs. 9.9 +/- 3.9 pmol/min/mg, P < 0.001), the activity in Lennox syndrome and myoclonic epilepsies being significantly higher than in those with absences and partial epilepsy. GABA-T activity did not correlate with doses or trough steady-state serum levels of VPA. Platelet GABA-T could be useful as a peripheral marker of GABAergic alterations and GABAergic effects of antiepileptic drugs in epileptic patients.

4-Aminobutyrate Transaminase↗
PubMed2006

Inhibition of rabbit brain 4-aminobutyrate transaminase by some taurine analogues: a kinetic analysis.

The use of the antiepileptic drug, 4-aminobutyrate transaminase (GABA-T) inhibitor vigabatrin (VIGA), has been recently cautioned because it is associated to irreversible field defects from damage of the retina. Since novel GABA-T inhibitors might prove useful in epilepsy or other CNS pathologies as VIGA substitutes, the aim of the present investigation was to characterize the biochemical properties of some taurine analogues (TA) previously shown to act as GABA-T inhibitors. These include (+/-)piperidine-3-sulfonic acid (PSA), 2-aminoethylphosphonic acid (AEP), (+/-)2-acetylaminocyclohexane sulfonic acid (ATAHS) and 2-aminobenzenesulfonate (ANSA). Kinetic analysis of the activity of partially purified rabbit brain GABA-T in the presence of VIGA and TA showed that PSA and AEP caused a linear, mixed-type inhibition (Ki values 364 and 1010 microM, respectively), whereas VIGA, ANSA and ATAHS behaved like competitive inhibitors (Ki values 320, 434 and 598 microM, respectively). Among the compounds studied, only VIGA exerted a time-dependent, irreversible inhibition of the enzyme, with Ki and k(inact) values of 773 microM and 0.14 min(-1), respectively. Furthermore, the ability of VIGA and TA to enhance GABA-ergic transmission was assessed in rabbit brain cortical slices by NMR quantitative analysis. The results demonstrate that VIGA as well as all TA promoted a significant increase of GABA content. In conclusion, PSA, ANSA and ATAHS, reversible GABA-T inhibitors with Ki values close to that of VIGA, represent a new class of compounds, susceptible of therapeutic exploitation in many disorders associated with low levels of GABA in brain tissues.

4-Aminobutyrate Transaminase↗
PubMed2006

Inactivation of GABA transaminase by 4-acryloylphenol.

Previous study showed that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. As a result, 4-acryloylphenol was synthesized as a 4-hydroxybenzaldehyde analogue, and shown to inactivate potently the enzyme in a time-dependent manner. The inactivation was protected by alpha-ketoglutarate, indicating that it occurs at the active site of the enzyme. Beta-mercaptoethanol also prevented the enzyme from inactivation. The possible mechanism involving a Michael addition was proposed to rationalize the inactivation.

4-Aminobutyrate Transaminase↗
PubMed2004

Age-related changes of gamma-aminobutyric acid transaminase immunoreactivity in the hippocampus and dentate gyrus of the Mongolian gerbil.

We investigated the age-related changes of gamma-aminobutyric acid transaminase (GABA-T, a GABA degradation enzyme) in the hippocampus and dentate gyrus of the gerbil at postnatal month 1 (PM 1), PM 3, PM 6, PM 12, and PM 24. Age-related changes of GABA-T immunoreactivity were distinct in the hippocampal CA1 region and in the dentate gyrus. GABA-T immunoreactivity was weak at PM 1, but at PM 3, it had increased significantly, and then increased further. Between PM 6 and PM 12, strong GABA-T immunoreactivity was found in nonpyramidal cells (GABAergic) in the stratum pyramidale of the CA1 region, and at PM 6, strong GABA-T immunoreactivity was found in neurons of the dentate gyrus subgranular zone. At PM 24, CA1 pyramidal cells showed strong GABA-T immunoreactivity. Western blot analysis showed a pattern of GABA-T expression similar to that shown by immunohistochemistry at various ages. In conclusion, our results suggest that the age-related changes of GABA-T provide important information about the aged brain with GABA dysfunction.

4-Aminobutyrate Transaminase↗
PubMed2006

Chronic hepatitis C in patients with persistently normal alanine transaminase levels.

BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.

Adult↗
PubMed2004

Transient elevation of liver transaminase after starting insulin therapy for diabetic ketosis or ketoacidosis in newly diagnosed type 1 diabetes mellitus.

A mild increase of AST and/or ALT is sometimes observed among patients with diabetic ketosis or diabetic ketoacidosis (DKA) after initial insulin treatment, and the exact mechanism is still undefined. Therefore, we compared the clinical background between patients with and without transient elevation of liver transaminase (TELT) at the onset of type 1 diabetes mellitus with diabetic ketosis or DKA. Among 50 patients, 13 patients showed TELT. The TELT group was characterized by higher plasma glucose (P<0.05), higher HbA1c (P<0.05), and higher triglyceride (P<0.01) before insulin therapy than those without TELT. The TELT group needed significantly more insulin (P<0.05) for the treatment. In echo-histogram analysis of three patients with TELT, the increase of liver-kidney contrast after insulin treatment suggested fat deposition to the liver. The fat deposition to the liver might be one of the causes of the mild increase of AST and/or ALT after initial treatment of insulin in diabetic ketosis or DKA.

Adult↗
PubMed2005

Virus and transaminase levels determine the emergence of drug resistance during long-term lamivudine therapy in chronic hepatitis B.

BACKGROUND/AIMS: The results of earlier studies on determinants for the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants (rtM204 I/V) were controversial. The aim was to evaluate the impact of viral factors, host factors, host-viral interaction and drug factor on the emergence of rtM204 I/V. METHODS: 56 non-cirrhotic and 58 cirrhotic patients received lamivudine therapy for a median of 34 (12-60) months. RESULTS: rtM204 I/V emerged in 37 noncirrhotic and 36 cirrhotic patients. Stepwise logistic regression analysis showed that baseline hepatitis B e antigen (HBeAg) status [odds ratio (OR), 7.728; 95% confidental interval (CI), 2.886-12.957; P=0.0026], HBV-DNA level (OR, 3.756; 95% CI, 1.058-5.089; P=0.0202), alanine transaminase (ALT) level (OR, 6.285; 95% CI, 1.057-11.990; P=0.00246) and treatment duration (OR, 19.88; 95% CI, 8.652-31.762; P<0.0004) were independent determinants for the emergence of rtM204 I/V. Further categorical analysis and correlation test disclosed that patients with HBeAg positivity, HBV-DNA>500 pg/ml and ALT <5x upper limit of normal had significantly higher mutation rates. CONCLUSIONS: HBeAg status, HBV-DNA, ALT levels and treatment duration are the major determinants for the YMDD mutation during lamivudine therapy, and should be considered in designing the therapeutic strategy.

Adult↗
PubMed2004

The role of glutamine transaminase K (GTK) in sulfur and alpha-keto acid metabolism in the brain, and in the possible bioactivation of neurotoxicants.

Glutamine transaminase K (GTK), which is a freely reversible glutamine (methionine) aromatic amino acid aminotransferase, is present in most mammalian tissues, including brain. Quantitatively, the most important amine donor in vivo is glutamine. The product of glutamine transamination (i.e., alpha-ketoglutaramate; alphaKGM) is rapidly removed by cyclization and/or conversion to alpha-ketoglutarate. Transamination is therefore "pulled" in the direction of glutamine utilization. Major biological roles of GTK are to maintain low levels of phenylpyruvate and to close the methionine salvage pathway. GTK also catalyzes the transamination of cystathionine, lanthionine, and thialysine to the corresponding alpha-keto acids, which cyclize to ketimines. The cyclic ketimines and several metabolites derived therefrom are found in brain. It is not clear whether these compounds have a biological function or are metabolic dead-ends. However, high-affinity binding of lanthionine ketimine (LK) to brain membranes has been reported. Mammalian tissues possess several enzymes capable of catalyzing transamination of kynurenine in vitro. Two of these kynurenine aminotransferases (KATs), namely KAT I and KAT II, are present in brain and have been extensively studied. KAT I and KAT II are identical to GTK and alpha-aminoadipate aminotransferase, respectively. GTK/KAT I is largely cytosolic in kidney, but mostly mitochondrial in brain. The same gene codes for both forms, but alternative splicing dictates whether a 32-amino acid mitochondrial-targeting sequence is present in the expressed protein. The activity of KAT I is altered by a missense mutation (E61G) in the spontaneously hypertensive rat. The symptoms may be due in part to alteration of kynurenine transamination. However, owing to strong competition from other amino acid substrates, the turnover of kynurenine to kynurenate by GTK/KAT I in nervous tissue must be slow unless kynurenine and GTK are sequestered in a compartment distinct from the major amino acid pools. The possibility is discussed that the spontaneous hypertension in rats carrying the GTK/KAT I mutation may be due in part to disruption of glutamine transamination. GTK is one of several pyridoxal 5'-phosphate (PLP)-containing enzymes that can catalyze non-physiological beta-elimination reactions with cysteine S-conjugates containing a good leaving group attached at the sulfur. These elimination reactions may contribute to the bioactivation of certain electrophiles, resulting in toxicity to kidney, liver, brain, and possibly other organs. On the other hand, the beta-lyase reaction catalyzed by GTK may be useful in the conversion of some cysteine S-conjugate prodrugs to active components in vivo. The roles of GTK in (a) brain nitrogen, sulfur, and aromatic amino acid/kynurenine metabolism, (b) brain alpha-keto acid metabolism, (c) bioactivation of certain electrophiles in brain, (d) prodrug targeting, and (e) maintenance of normal blood pressure deserve further study.

Amino Acids, Sulfur↗
PubMed2006

Acute regulation of steady-state GABA levels following GABA-transaminase inhibition in rat cerebral cortex.

Cellular GABA levels are determined by the dynamic balance between synthesis and catabolism and are regulated at the level of glutamate decarboxylase, precursor availability (e.g., glutamate and glutamine), and possibly GABA degradation. GABA levels rise and stabilize within hours in human cortex following orally administered vigabatrin, an irreversible inhibitor of GABA-T, suggesting potential product inhibition of GABA synthesis or enhanced GABA degradation through the non-inhibited GABA-T fraction. In this study time courses of the rise in cortical GABA were measured in anesthetized rats in vivo after vigabatrin treatment using localized (1)H magnetic resonance spectroscopy and the times to reach steady-state for a given dose were determined. Rates of GABA synthesis were estimated for the period of constant GABA level from the accumulation of [2-(13)C]GABA following a short intravenous infusion (20 min) of either [1,6-(13)C(2)]glucose or [2-(13)C]acetate. No evidence of product inhibition of glutamate decarboxylase by the increased GABA concentration or reduced synthesis from [1,6-(13)C(2)]glucose (control, 0.031+/-0.010; vigabatrin-treated, 0.037+/-0.004 micromol/g/min, P=0.30) or [2-(13)C]acetate (control, 0.078+/-0.010; vigabatrin-treated, 0.084+/-0.006 micromol/g/min, P=0.42) was found. Fractional changes in steady-state GABA levels and GABA-T activities 5-6 h after vigabatrin treatment were approximately equal. The lack of change in GABA synthesis (and GABA catabolic flux for constant GABA levels) suggests that GABA-T has a near-zero flux control coefficient in vivo-capable of greatly altering the steady-state GABA concentration but exerting little or no control on GABA synthesis or GABA/glutamine cycling flux. The findings are consistent with a Michaelis-Menten kinetic model whereby cellular GABA levels increase until flux through the remaining (uninhibited) transaminase equals the rate of GABA synthesis. The findings suggest that astroglia may be the site of continuing GABA catabolism after acute vigabatrin treatment.

4-Aminobutyrate Transaminase↗
PubMed2004

Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices.

Phenylethylidenehydrazine (PEH), an analog of the monoamine oxidase inhibitor, beta-phenylethylhydrazine (phenelzine), inhibits the gamma-aminobutyric acid (GABA) catabolic enzyme GABA-transaminase and increases brain levels of GABA. GABA is the predominant fast inhibitory transmitter counteracting glutamatergic excitation, and increased neural GABA could influence a wide range of synaptic and circuit properties under both physiologic and pathophysiologic conditions. To examine the scope of these effects, we applied PEH (or vehicle) to rat hippocampal slices and measured basal glutamatergic transmission, synaptic plasticity, and epileptiform activity using extracellular field and whole cell patch clamp recordings. In vitro pre-treatment with PEH (100 microM) increased the GABA content of hippocampal slices by approximately 60% over vehicle-treated controls, but it had no effect on basal field excitatory postsynaptic potentials, tonic GABA currents, paired-pulse facilitation, or long-term potentiation. In contrast, pre-incubation with PEH caused a dose- and time-dependent reduction in epileptiform burst frequency induced by superfusion with Mg2+-free or high-K+ artificial cerebrospinal fluid. Thus, the inhibitory effects of PEH are state-dependent: hyper-excitation during epileptiform bursting was reduced, whereas synaptic transmission and plasticity were unaffected.

4-Aminobutyrate Transaminase↗
PubMed1996

Effects of chronic oral treatment with GABA-transaminase inhibitors on the GABA system in brain, liver, kidney, and plasma of the rat.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is not solely located in the CNS, it and the enzymes responsible for its synthesis (glutamic acid decarboxylase, GAD, EC 4.1.1.15) and catabolism (GABA-transaminase, GABA-T, EC 2.6.1.19) are also present in non-neuronal organs. Following 2, 8 and 21 day oral administration of ethanolamine-O-sulphate (EOS) and gamma-vinyl GABA (GVG), two irreversible inhibitors of GABA-T, the GABA content and activities of GAD and GABA-T in rat brain, liver and kidney, and the GABA content of plasma were determined: GABA-T activity was significantly decreased (over 80%) in liver, brain and kidney, although there was 2-3 times the residual activity left in the brain compared with the peripheral organs. GABA content was subsequently significantly elevated in the liver (300-1500%), plasma (200-300%) and brain (200-300%), although, surprisingly, the kidney GABA content was reduced (by 60-70%) compared with control. GAD activity was decreased following 8 day treatment in liver and brain. Kidney GAD was reduced at all time points. These two compounds are anticonvulsant, GVG is used clinically for the treatment of epilepsy but it seems that these drugs have significant peripheral effects.

4-Aminobutyrate Transaminase↗
PubMed2001

Glutamine is the major precursor for GABA synthesis in rat neocortex in vivo following acute GABA-transaminase inhibition.

The objective of the present study was to assess the degree to which astrocytic glutamine provides carbon for net synthesis of GABA in the rat neocortex in vivo. Isotopic labeling of GABA and glutamate from astrocytic glutamine was followed in halothane anesthetized and ventilated rats during an intravenous infusion of [2-(13)C]glucose. A net increase in GABA was achieved by administration of the GABA-transaminase inhibitor, gabaculine to suppress catabolism of GABA and recycling of (13)C label. (13)C Percentage enrichments of GABA, glutamate and glutamine were assessed in tissue extracts using (13)C-edited (1)H nuclear magnetic resonance at 8.4 T. GABA levels increased 2.6 micromol/g at 2 h and 6.1 micromol/g at 5 h after gabaculine, whereas glutamate and glutamine decreased in toto by 5.6 micromol/g at 2 h and 3.1 micromol/g at 5 h. Selective enrichment of glutamine, glutamate, and GABA C3's over other carbon positions was observed consistent with a precursor role for astrocytic glutamine. Between 1 h (control) and 3 h (gabaculine-treated) of [2-(13)C]glucose infusion, (13)C percentage enrichment increased in glutamine C3 (from 3.2+/-0.5 to 7.0+/-0.9%), glutamate C3 (from 1.8+/-0.5 to 3.4+/-0.9%), and GABA C3 (from 2.7+/-1.6 to 4.8+/-0.4%). The measured incremental [3-(13)C]GABA concentration (0.15 micromol/g) was close to the predicted value (0.13 micromol/g) that would be expected if the increase in GABA were produced entirely from glutamine compared to glutamate (0.07 micromol/g) based on the average precursor enrichments between 1 and 3 h. We conclude that glutamine is the major source of GABA carbon in the rat neocortex produced acutely following GABA-T inhibition by gabaculine in vivo.

4-Aminobutyrate Transaminase↗
PubMed2003

Glutamate-pyruvate transaminase protects against glutamate toxicity in hippocampal slices.

Elimination of glutamate through enzymatic degradation is an alternative to glutamate receptor blockade in preventing excitotoxic neuronal injury. Glutamate pyruvate transaminase (GPT) is a highly active glutamate degrading enzyme that requires pyruvate as a co-substrate. This study examined the ability of GPT to protect neurons of the hippocampal slice preparation against glutamate toxicity. Two methods were used to elevate the concentration of glutamate in the peri-neuronal space. In an endogenous release paradigm, slices were incubated with 100-500 microM L-trans-pyrrolidine-2,4-dicarboxylate (PDC), an inhibitor of glutamate re-uptake. One hour of exposure to PDC in normal, pyruvate-free slice maintenance medium caused a dose dependent increase in neuronal death assessed 24 h later by propidium iodide uptake in dead cell nuclei. GPT (10 U/ml) decreased neuronal death caused by exposure to PDC at all PDC concentrations tested. Neuroprotection in this model was not dependent on added or non-physiologic levels of pyruvate. In a different paradigm, glutamate was added directly to the normal, pyruvate-free slice maintenance medium and not rinsed away, exposing the slices to a range of 1-5 mM glutamate for an extended period. Twenty-four hours later, neuronal death was again assessed by propidium iodide uptake. GPT was again neuroprotective, decreasing neuronal death in the range from 3 to 5 mM glutamate. In the setting of incubation with this large load of glutamate, neuroprotection by GPT was enhanced by adding pyruvate to the medium. GPT is an effective neuroprotectant against glutamate excitotoxicity. When exposure is limited to endogenously released glutamate, neuroprotection by GPT is not dependent on added pyruvate.

Alanine Transaminase↗