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PubMed1987

Rapid changes in serum, plasma and erythrocyte lipid compositions, and serum transaminase levels during continuous enteral hyperalimentation by carbohydrates alone.

Twelve normal men received twice their estimated basal energy requirement by a carbohydrate solution via a nasogastric catheter during 48 hours, followed by a seven-hour fast. Subsequently, in nine of them 0.5 mg epinephrine was given subcutaneously under ongoing fasting. During hyperalimentation, serum triglycerides, phospholipids, total and free cholesterol, phospholipids/free cholesterol ratio, and plasma free fatty acids decreased, whereas the percentage of free cholesterol increased. During fasting and subsequent epinephrine administration triglycerides and free fatty acids rose without reaching basal levels. Plasma and red blood cell (RBC) fatty acid composition already changed from two hours after the start of the feeding. Most markedly, a steady decrease in RBC 18:2c, omega 6, amounting to more than 17% of the basal value at the end of the observation period was found. Neither in plasma, nor in RBC a concomitant appearance of 20:3c, omega 9 was seen. In RBC, the relative amounts of the saturated fatty acids increased, whereas those of monounsaturated and polyunsaturated fatty acids decreased. RBC content of total fatty acids decreased and that of cholesterol increased. The ratios 16:1c, omega 7/16:0 and 18:3c, omega 6/18:2c, omega 6 in plasma, and 20:3c, omega 6/18:2c, omega 6 in plasma and RBC increased, whereas those of 18:1c, omega 7/16:1c, omega 7 and 20:3c, omega 6/18:3c, omega 6 in plasma decreased. After 48 hours feeding serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels were moderately increased and rose further during fasting. Thus, continuous enteral hyperalimentation by carbohydrates alone rapidly induces profound changes in serum-, plasma-, and RBC lipid compositions and serum parameters of hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Contrasting effects of the GABA transaminase inhibitors gamma-vinylGABA and aminooxyacetic acid on arterial pressure following injection into nucleus tractus solitarius.

The effect of injection of inhibitors of GABA-transaminase into the nucleus tractus solitarius (NTS) on arterial pressure was examined in anesthetized rats. Two typical GABA-transaminase inhibitors, gamma-vinylGABA (GVG) and aminooxyacetic acid (AOAA), increased arterial pressure when injected into the NTS, a response similar to that elicited by direct stimulation of GABA receptors in the NTS. However, with neither drug was the response consistent with the action of inhibiting GABA-T. The response elicited by GVG, despite GVG acting as an irreversible inhibitor of GABA-T, could be reproduced with subsequent injections. Still, the pressor response to GVG could be reversed by blockade of GABAB-receptors with CGP-35348, suggesting that GVG injection did increase GABA-mediated neural transmission. In contrast, the pressor response to AOAA could not be antagonized by blockade of either GABAA or GABAB receptors. These results suggest that acute inhibition of GABA-T does not necessarily result in an increase in GABA-mediated neural transmission.

4-Aminobutyrate Transaminase↗
PubMed1990

Copulatory thrusting pattern in the male rat after acute treatment with GABA transaminase inhibitors.

It has previously been found that the GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate reduced intromission behavior in male rats without affecting mounting behavior. These effects were obtained, however, only in doses that also impaired motor execution. The purpose of the present study was to establish whether copulatory thrusting patterns were affected by these GABA transaminase inhibitors. Sodium valproate, 200 mg/kg, reduced the number of intromissions and the intromission rate without affecting mounting behavior. GAG, 100 mg/kg, had similar effects on sexual behavior. The only effect obtained on copulatory thrusting patterns was a small reduction in mount and intromission thrust frequency after GAG 100 mg/kg. It is unlikely that this effect is responsible for the inhibitory actions of GAG on sexual behavior, especially since sodium valproate did not modify copulatory thrusting patterns, but inhibited sexual behavior in a manner similar to that of GAG.

4-Aminobutyrate Transaminase↗
PubMed1991

Sexual behavior and copulatory thrusting patterns in male rabbits treated with GABA transaminase inhibitors.

The effects of enhanced central nervous system GABA levels on sexual behavior and copulatory pelvic thrusting were evaluated in male New Zealand white rabbits. The GABA transaminase inhibitors sodium valproate and gamma-acetylen GABA (GAG), in doses of 100 and 200 mg/kg and 50 and 100 mg/kg, respectively, were intraperitoneally administered and sexual behavior recorded at several intervals after drug administration. At the same time, copulatory thrusting was registered using a polygraphic technique. Tests for gross motor functions were also performed. None of the drugs had any effect in these latter tests. Sodium valproate, in a dose of 100 mg/kg, had a slight inhibitory effect on sexual behavior at 280 min postinjection. A dose of 200 mg/kg inhibited sexual activity already 15 min postinjection, and the effect lasted for at least 280 min. GAG, 100 mg/k, inhibited mounting behavior at 8 h postinjection, and ejaculation was reduced from 2 to at least 8 h postinjection. Copulatory thrusting patterns were not affected by the drug treatments. These data suggest that increased GABAergic activity reduces sexual arousal in the rabbit. GABA does not seem to be critically involved in the regulation of the motor patterns underlying pelvic thrusting. There are important quantitative and qualitative differences between rats and rabbits with regard to the actions of GABA transaminase inhibitors upon sexual functions.

4-Aminobutyrate Transaminase↗
PubMed1987

Differential effects of GABA transaminase inhibitors on sexual behavior, locomotor activity, and motor execution in the male rat.

The GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate were administered intraperitoneally and their effects on locomotor activity, motor execution and sexual behavior were analyzed. It was found that sodium valproate, administered 15 min before observation, reduced locomotor activity only at a dose of 200 mg/kg. Doses of 100 and 400 mg/kg had no effect. Motor execution was impaired in a dose-dependent way, the lowest effective dose being 200 mg/kg. Sexual behavior was also dose-dependently reduced. Sodium valproate, administered 60 min before observation, inhibited all behaviors. The lowest effective dose was 200 mg/kg for locomotor activity and 400 mg/kg for motor execution and sexual behavior. GAG also inhibited all behavior, in doses ranging from 25 mg/kg (locomotor activity) to 100 mg/kg (motor execution and sexual behavior). The data showed that there is no relation between effects on locomotor activity and the effects on sexual behavior, whereas sexual behavior is inhibited whenever motor execution is impaired. Moreover, there is no correlation between effects on locomotor activity and motor execution. It is suggested that GABA transaminase inhibitors effect sexual behavior only indirectly, via an impairment of motor execution. Therefore it is doubtful whether GABAergic mechanisms play any role in the normal regulation of sexual behavior.

4-Aminobutyrate Transaminase↗
PubMed1985

Purification and characterization of rat kidney L-alanine: 4,5-dioxovalerate transaminase and inhibition by hemin.

Rat kidney L-alanine:4,5-dioxovalerate transaminase (EC 2.6.1.43), which may be involved in the formation of aminolevulinic acid in mammalian cells, was purified 82-fold to apparent homogeneity with a 19% yield. Molecular weight of the enzyme, as estimated by gel filtration, was found to be 225 000. In polyacrylamide gel electrophoresis under denaturing conditions, the enzyme moved as a single band corresponding to an Mr of 37 000, suggesting that the enzyme is composed of six identical subunits. The Km values of L-alanine and 4,5-dioxovalerate are 2.9 and 0.25 mM, respectively. The enzyme had an optimum activity at pH 6.6 and was most active at 65 degrees C. Among some amino acids tested, L-alanine proved to be the most efficient amino donor, and the enzyme was also stereospecific for the L-isomer. The effect of intermediate metabolites of heme biosynthesis, for example, delta-aminolevulinic acid, protoporphyrin, hemin and bilirubin has been studied on purified L-alanine:4,5-dioxovalerate transaminase. Amongst these metabolites, hemin and protoporphyrin were found to be effective inhibitors.

Animals↗
PubMed1986

Psychophysiological and psychometric studies after manipulating the GABA system by vigabatrin, a GABA-transaminase inhibitor.

This study is concerned with the alterations in central and peripheral psychophysiological measures and psychometric variables after experimental manipulation of the most important inhibitory transmitter system of the CNS, the gamma-aminobutyric acid (GABA) system. Vigabatrin (GVG), a new enzyme-activated, irreversible inhibitor of GABA transaminase, which increases cerebrospinal fluid concentrations of GABA and other substrates of GABA transaminase, was given in single oral doses of 1 g, 2 g and 3 g to 10 normal healthy volunteers. In this double-blind, placebo-controlled crossover study, 3 mg lorazepam was given as reference compound. Blood sampling for vigabatrin kinetics, EEG recordings and evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 1, 2, 4, 6, 8 and 24, and psychometric tests at the same times (except the first hour). Pharmacokinetic analyses demonstrated good absorption of GVG with peak plasma concentrations found within the first two hours, dose-dependent areas under the plasma concentration-time curves and about 65% recovery in the 24-h urine. Computer-assisted spectral analysis of the EEG suggested that GVG produces only small changes in the normal CNS, characterized by an augmentation of total power, absolute and relative power of the beta activity and acceleration of the centroid of the total activity. There was also a trend towards an increase of alpha activity and of the absolute and relative power of the dominant frequency, decrease in the alpha centroid and increase of the centroid of the combined delta and theta activity. Lorazepam 3 mg, in contrast, produced highly significant changes characterized by a decrease of total power, alpha activity, absolute and relative power of the dominant frequency and centroid of the combined delta and theta activity, while beta activity as well as the centroid of the alpha, beta and total activity increased. In the resting condition an additional augmentation of slow activity suggested hypnotic properties of 3 mg lorazepam. The latter changes are typical for anxiolytic sedatives and were also reflected at the behavioral level where psychometric data demonstrated a deterioration in the noo- and thymopsychic parameters and sedative effects in psychophysiological variables. GVG, on the other hand, produced only subtle changes characterized by an improvement of noo- and thymopsychic variables and vegetative activation.

4-Aminobutyrate Transaminase↗
PubMedDate not supplied

Human brain GABA transaminase is immunologically distinct from those of other mammalian brains.

Monoclonal antibodies (mAbs) to bovine brain gamma-aminobutyric acid (GABA) transaminase were characterized by epitope mapping analysis, and used as probes to compare the epitopes of the enzymes from several mammalian brains including man. From the epitope mapping analysis, three subgroups of mAbs recognizing different peptide fragments were identified. In the immunoblots probed with the mAbs, only one out of the three subgroups of mAbs reacted with a protein band of 50 kDa from human brain; the two other mAbs failed to detect any signal on the blots. In contrast, all of the mAbs did recognize a GABA-T protein band on immunoblots of all other mammalian brains tested. The results suggest that human brain GABA transaminase is immunologically distinct from those of other mammalian brains.

4-Aminobutyrate Transaminase↗
PubMed1984

Reduced GABA transaminase activity in the Huntington's disease putamen.

GABA transaminase activity is reduced in autopsied putamen samples from patients dying with Huntington's disease. Its activity is also reduced in the striatum of rats previously lesioned with kainic acid. In both cases, the reduction in GABA transaminase activity is comparable with the reduction in glutamate decarboxylase activity, supporting the suspected localization of this enzyme to GABA neurones within the basal ganglia.

4-Aminobutyrate Transaminase↗
PubMed1986

Nitrogen-13 flux from L-[13N]glutamate in the isolated rabbit heart: effect of substrates and transaminase inhibition.

Kinetic and biochemical parameters of nitrogen-13 flux from L-[13N]glutamate in myocardium were examined. Tissue radioactivity kinetics and chemical analyses were determined after bolus injection of L-[13N]glutamate into isolated arterially perfused interventricular septa under various metabolic states, which included addition of lactate, pyruvate, aminooxyacetate (a transaminase inhibitor), or a combination of aminooxyacetate and pyruvate to the standard perfusate containing insulin and glucose. Chemical analysis of tissue and effluent at 6 min allowed determination of the composition of the slow third kinetic component of the time-activity curves. 13N-labeled aspartate, alanine and glutamate accounted for more than 80% of the tissue nitrogen-13 under the experimental conditions used. Specific activities for these amino acids were constant, but not identical to each other, from 6 through 15 min after administration of L-[13N]glutamate. Little labeled ammonia (1.9%) and glutamine (4.7%) were produced, indicating limited accessibility of exogenous glutamate to catabolic mitochondrial glutamate dehydrogenase and glutamine synthetase, under control conditions. Lactate and pyruvate additions did not affect tissue amino acid specific activities. Aminooxyacetate suppressed formation of 13N-labeled alanine and aspartate and increased production of L-[13N]glutamine and [13N]ammonia. Formation of [13N]ammonia was, however, substantially decreased when aminooxyacetate was used in the presence of exogenous pyruvate. The data support a model for glutamate compartmentation in myocardium not affected by increasing the velocity of enzymatic reactions through increased substrate (i.e., lactate or pyruvate) concentrations but which can be altered by competitive inhibition of transaminases (via aminooxyacetate) making exogenous glutamate more available to other compartments.

Acetates↗
PubMed1992

Beta-alanine transaminase activity in black and suppressor of black mutations of Drosophila melanogaster.

An assay for beta-alanine transaminase activity in extracts of Drosophila melanogaster has been developed. By use of this assay, the levels of beta-alanine transaminase activity in several strains of flies has been examined as a function of developmental age. The black mutation shows elevated levels of activity compared to wild type, while suppressor of black strains show decreased levels compared to wild type.

4-Aminobutyrate Transaminase↗
PubMed1988

Acquisition of new metabolic capabilities: multicopy suppression by cloned transaminase genes in Escherichia coli K-12.

The four general transaminases of Escherichia coli K-12 have overlapping, but discrete, substrate specificities and participate in the final step in the synthesis of at least seven different amino acids. Through the use of strains that have mutations in one or more transaminase genes and carry a different wild-type (wt) gene on a multicopy plasmid, it was possible to detect instances in which an amplified wt gene suppressed nonallelic mutations. In these cases, overproduction of the enzyme permitted a broader range of substrates to be used at physiologically significant levels, either because a low catalytic efficiency (in the case analyzed here) or a low affinity of the enzyme towards the substrate prevented its effective utilization under normal conditions. Consequently, by compensating for a low catalytic reaction rate, enzyme overproduction circumvents the original lesion and restores biosynthetic activity to the mutant strain. The suppression of a mutation in one gene by amplified copies of a different wt gene is termed 'multicopy suppression'. This phenomenon is useful for detecting poorly expressed genes, for detecting duplicate genes, for identifying secondary functions of the products of known genes, and for elucidating the metabolic role of the product of the suppressed gene.

Cloning, Molecular↗
PubMed1981

Isolated and combined effects of pesticides on serum transaminases in Mystus vittatus (African catfish).

Alterations in serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels of Mystus vittatus (African catfish) after exposure to subacute concentrations of thiotox (T), dichlorvos (D), and carbofuran (C) and their combinations C/T (antagonistic), T/D (additive) and (T + D)/C (synergistic) for a period of 30 days have been investigated. Alterations were more evident in SGOT than in SGPT. Maximum (92.5%) elevation was observed with SGOT at the highest concentration of (T + D)/C combination and the lowest (14.76%) at the lowest concentration of T/D combination. Significant (P less than 0.05) stimulation was observed except at the lowest concentration after all treatments.

Alanine Transaminase↗
PubMed1984

Mercuric chloride stress on serum transaminase activity in Notopterus notopterus.

Mercuric intoxication at sublethal levels (1/5, 1/10, 1/15, 1/20 or 1/25 fractions of 96 h LC50) produced alterations in the activity of serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) of Notopterus notopterus. The difference between control and treated fish was found to be significant at P less than 0.05, P less than 0.01 and P less than 0.001 levels. Maximum (81.75%) significant (P less than 0.001) effect was observed in SGOT: maximum (69.23%) significant (P less than 0.001) effect was observed in SGPT in fish exposed for 60 days.

Alanine Transaminase↗
PubMed2004

Inverse association between serum adiponectin level and transaminase activities in Japanese male workers.

BACKGROUND/AIMS: Since a novel polypeptide named adiponectin was shown to prevent the development of steatosis and steatohepatitis in animal models, we studied whether it was also possible in a clinical situation. METHODS: Associations between serum adiponectin levels and serum transaminase activities were studied in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV- or HCV-induced liver diseases. RESULTS: Various markers of metabolic diseases including levels of body mass index (BMI), serum triglyceride, total cholesterol, and insulin resistance assessed by the homeostasis model were significantly higher in subjects with increased transaminase activities when compared to those with normal activities. Single regression analyses demonstrated that the logarithmic serum adiponectin level was inversely correlated with the levels of logarithmic serum AST (r=-0.229, P<0.0001), ALT (r=-0.305, P<0.0001), and gammaGTP (r=-0.278, P<0.0001). Even in multiple regression analyses in which subjects' age and levels of BMI, serum triglyceride, total cholesterol, and insulin resistance were adjusted, the inverse correlations were significant (P=0.0426, 0.0332, and 0.0011, respectively). CONCLUSIONS: Hypoadiponectinemia may worsen liver diseases associated with metabolic diseases in clinical cases. In addition to aggravation of insulin resistance and hyperlipidemia, some hypoadiponectinemia specific mechanisms may stand behind the association.

Adiponectin↗
PubMed2006

Diagnostic and predictive factors of significant liver fibrosis and minimal lesions in patients with persistent unexplained elevated transaminases. A prospective multicenter study.

BACKGROUND/AIMS: In patients with unexplained elevated transaminases, prognosis of the liver disease and factors associated with increased risk of liver fibrosis and normal/subnormal liver are unknown. The aim of this prospective study was to identify diagnosis and clinical and biological factors associated with significant (bridging) fibrosis and minimal lesions of the liver in patients with persistent unexplained elevated ALT levels. METHODS: From July 2002 through October 2004, all consecutive asymptomatic patients with unexplained chronically elevated ALT levels were included. All patients had clinical, biological, ultrasonographic examination and a liver biopsy. RESULTS: 272 patients (60.3% males, mean age 46.4 years, BMI 26.7) were included. Pathological findings were: minimal lesions (18.7%), steatosis (26.8%), NASH (32.7%), and miscellaneous (21.7%). Significant fibrosis was found in 27.4% of cases, including 9 cases of cirrhosis. By multivariate analysis, independent predictors of significant fibrosis were tobacco use (OR 2.5, 95% CI 1.34-4.74 p=0.04), BMI>25 (2.49, 1.31-4.73 p=0.005) and diabetes (4.41, 1.73-11.29 p=0.002). Independent factors associated with minimal lesions were female gender (OR 3.4 95% CI 1.73-6.75 p<0.0001) and BMI<25 (3.55, 1.8-6.98, p<0.0001). CONCLUSIONS: In patients with unexplained chronically elevated transaminases, significant fibrosis is statistically associated with tobacco use, BMI>25 and diabetes, and minimal lesions are significantly associated with female gender and BMI<25.

Adult↗
PubMed2005

Hyperinsulinemia predicts hepatic fat content in healthy individuals with normal transaminase concentrations.

Although the prevalence of insulin resistance (IR) and compensatory hyperinsulinemia (CH) is increased in patients with nonalcoholic fatty liver disease, the role of IR/CH in regulation of hepatic fat content in healthy volunteers with normal concentrations of alanine transaminase (ALT) has not been defined. To address this issue, hepatic fat content was quantified by ultrasound in 69 (30 men, 39 women) healthy individuals, without known risk factors for liver disease and with plasma ALT concentrations of less than 30 U/L. Experimental variables quantified included body mass index, waist circumference, systolic and diastolic blood pressures, and fasting plasma glucose, fasting plasma insulin (FPI), and lipid concentrations. Subjects were classified as having no (55%), mild (27%), or moderate to severe (18%) hepatic steatosis on the basis of the ultrasound results. Statistically significant (P < .05-.001) correlations (Spearman rho values) existed between liver fat content and ALT (0.26), body mass index (0.52), waist circumference (0.50), systolic blood pressure (0.28), diastolic blood pressure (0.27), fasting plasma glucose (0.47), FPI (0.56), triglycerides (0.30), and high-density lipoprotein cholesterol (-0.35). Multivariate general discriminant analysis and multiple linear regression analysis indicated that FPI was the only independent predictor (P < .001) of both liver fat content and ALT concentrations. Fasting plasma insulin (a surrogate estimate of IR/CH) predicts hepatic fat content and ALT in healthy volunteers with normal transaminase concentrations, independently of the other anthropometric and metabolic variables measured.

Aged↗
PubMed2003

The role of elevated liver transaminase levels in children with blunt abdominal trauma.

The role of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels on intra-abdominal injury in children has not been adequately studied. In this report, the accuracy of these tests in predicting the degree and extend of intra-abdominal and hepatic injury in children with blunt abdominal trauma was investigated.Eighty-seven haemodynamically stable children with multiple trauma were prospectively evaluated. The SGOT and SGPT of patients with and without abdominal trauma (Groups I and II) were compared. Patients with and without radiologically verified intra-abdominal injury were further compared (Groups Ib and Ia). There was significant difference in SGOT and SGPT levels of Groups I and II. SGOT and SGPT levels were 333.6+/-283.8 and, 197.5+/-192.5 U/l, respectively in Group Ib; but 84.2+/-55.9, 43+/-29.8 U/l in Group Ia (P<0.001). In all patients with radiologically detected intra-abdominal pathology SGOT and SGPT levels were above 110.5 and 63.5 U/l, respectively. In patients with hepatic injury SGOT level was above 500 U/l and, SGPT level was above 300 U/l. Statistically significant positive correlation was found between radiologically detected intra-abdominal pathology and increased SGOT (above 110.5 U/l) and SGPT (above 63.5 U/l) levels (P<0.05). These data indicated that the SGOT and SGPT levels were significantly higher in patients with intra-abdominal injury even in the absence of hepatic injury. We suggest that liver function tests may be used as screening tests in children with blunt abdominal trauma in addition to physical abdominal examination. A sudden rise up to 110.5 U/l in SGOT and 63.5 U/l in SGPT indicate an intra-abdominal injury and severe hepatic injury should be suspected with higher levels of SGOT and SGPT.

Abdominal Injuries↗