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Anorectic potency of inhibiting GABA transaminase in brain: studies of hypothalamic, dietary and genetic obesities.

A variety of recent literature suggests that brain gamma-aminobutyric acid (GABA) plays an important role in the control of feeding. One such line of evidence is that pharmacological inhibition of brain GABA transaminase (GABA-T) produces dose-dependent anorexia in otherwise normal rats. To determine the generality of these findings we tested the ability of the GABA-T inhibitor ethanolamine-O-sulfate (EOS), to produce anorexia in three animal models of obesity: rats with medial hypothalamic lesions, rats exposed to palatable foods or Zucker fatty rats. Following intracisternal injection of 100, 200 or 400 micrograms EOS, all three models of chronic overeating showed dose-dependent anorexia of similar magnitude and duration to that seen in appropriate controls. These observations provide empirical support for previous suggestions that treatments which enhance brain GABA neurotransmission merit investigation for their potential use in treating excess energy consumption.

4-Aminobutyrate Transaminase↗

A study on the effects of severe repetitive exercise on serum myoglobin, creatine kinase, transaminases and lactate dehydrogenase.

Two groups of young men taking part in a 24-day training course involving increasingly severe exercise were studied. Serum myoglobin, creatine kinase, creatine kinase-MB, transaminases, lactate dehydrogenase, urea, creatinine, calcium and uric acid were estimated at intervals. During the first few days, increases in myoglobin and muscle enzymes correlated with the severity of the preceding exercise. Increases in myoglobin and muscle enzymes after the final most severe exercising were less than with the initial exercising, demonstrating the effect of physical training. The changes in myoglobin and the muscle enzymes correlated closely. Elevated myoglobin levels persisted for over 24 hours. There was no consistent correlation between changes in myoglobin and uric acid, both of which have been considered responsible for the renal failure which may occur with rhabdomyolysis.

Adult↗

[New aspects of the effect of isoniazid on transaminase activity in tuberculosis].

New evidence is obtained for inhibitory effect of isoniazid on activity of transaminases in prolonged application of the drug. Increase in the isoniazid inhibitory effect on alanine aminotransferase activity was shown to correlate with elevated concentration of Cu2+ in blood serum arising in experimental tuberculosis. Cu2+ and Co2+ caused the increase in the inhibitory effect of isoniazid due to their incorporation into structure of the preparation. The microelements, combined with pyridoxine, inhibited alanine aminotransferase and vice versa activated aspartate aminotransferase.

Alanine Transaminase↗

Purification and some properties of L-alanine:4,5-dioxovaleric acid transaminase from rat liver mitochondria.

L-alanine:4,5-dioxovalerate transaminase (EC 2.6.1.44) has been purified to homogeneity from rat liver mitochondria. Molecular weight of the native enzyme is estimated to be 230,000 +/- 3000 by gel filtration. Under denaturing condition, the dissociated enzyme has a subunit of approximately 41,000 +/- 2000, indicating the enzyme apparently is composed of six identical subunits. The enzyme is heat stable and has optimal activity at pH 6.9. Km values for L-alanine and 4,5-dioxovalerate are 3.3 X 10(-3) M and 2.8 X 10(-4) M respectively. Excess dioxovalerate inhibits the enzyme activity. Pyridoxal phosphate and dithiothreitol also inhibit the enzyme activity.

Animals↗

[The effect of long-term plasmapheresis on the composition of blood. III. Changes in the concentration of total, direct and indirect bilirubin, alkaline phosphatase, serum transaminases (SGOT, SGPT). total lipids, triglycerides and cholesterol].

In the group of blood donors submitted to the long term plasmapheresis with the weekly withdrawal of 370--670 ml of plasma, the concentrations of total bilirubin, alkaline phosphatase, aspartate (GOT) and alanine (GPT) transaminases, total lipids, triglycerides and cholesterol were not significantly changed (P greater than 0,05). The mean concentration of total lipids in plasma donors were close to the upper normal limit, while the concentrations of triglycerides slightly increased simultaneously with the increase of the number of plasmapheresis. The mean concentrations of indirect bilirubin significantly decreased (P less than 0,05) and the concentrations of indirect bilirubin increased (P less than 0,05), but because they do not differ significantly from the concentrations of the control group, these changes are of no clinical importance.

Alanine Transaminase↗

The serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase ratio as a prognostic index in severe acute viral hepatitis.

The SGOT/SGPT ratio was studied in 25 patients with severe acute viral hepatitis due to either B or non A-non B hepatitis. The transaminase levels were performed within 10 days of onset of the hepatitis or within 4 days of the diagnosis of fulminant hepatic failure. Twelve patients died of their acute illness. There was a significant difference between the SGOT/SGPT ratios of females who died mean = 2.05) and lived (mean 0.45) (p less than 0.001) and between the SGOT/SGPT ratios of males who died (mean - 1.01) and lived (mean 0.45) (p less than 0.02). Using 95% confidence intervals the expected ratios for combined sexes were calculated to be 0.31 to 0.63 for survivors and from 1.20 to 2.26 for nonsurvivors. Neither age not viral etiology affected the prognosis in this study.

Acute Disease↗

Linkage of atypical vitelliform macular dystrophy (VMD-1) to the soluble glutamate pyruvate transaminase (GPT1) locus.

One hundred twenty-eight blood samples were drawn from members of a single family with atypical vitelliform macular dystrophy (VMD-1) characterized by variable expressivity in affected members of at least 5 generations. Because of the late onset of detectable retinal lesions in most family members, phenotype data from only 93 individuals who were at least 14 years of age were analyzed for linkage. Phenotype data from the remaining 35 members of the family who were under age 14 were excluded from the analysis. Maximum-likelihood analysis for linkage between VMD-1 and 13 biochemical and serological markers in the family demonstrated linkage between VMD-1 and the soluble glutamate pyruvate transaminase (GPT1) locus, which has been tentatively assigned to the short arm of chromosome 16. A maximum lod score of Z = 4.34 (odds favoring linkage of approximately 22,000 to 1) was obtained at a recombination fraction of theta = .05.

Adolescent↗

Two previously undetected variants of glutamic-pyruvic transaminase found by acidic polyacrylamide gel electrophoresis.

Two new electrophoretic variants of glutamic-pyruvic transaminase (GPT) have been found by polyacrylamide gel electrophoresis at acidic pH. They appeared to represent a single allele, GPT 2, by the standard method of starch gel electrophoresis. Studies in families show that they are inherited as codominant alleles at the GPT locus. Population frequencies are about the same as those of other rare GPT variants. Their behavior on gels is consistent with both of them having substitutions of histidines in place of uncharged amino acids.

Alanine Transaminase↗

Absence of red cell glutamic-pyruvate transaminase: discovery of a "silent" allele homozygote.

An individual with complete absence of red blood cell glutamic-pyruvate transaminase (GPT) activity has been discovered in a South African family of Lebanese origin. The subject, who also shows a low level of serum GPT, appears to be perfectly healthy. His children, all obligatory heterozygotes for the GPT0 allele, have lower than average levels of the red cell enzyme. An apparent instance of anomalous segregation of red cell GPT resulting from the inheritance of the GPT0 allele was recorded in one of the proband's grandchildren.

Alanine Transaminase↗

Mechanism-based inactivation of pig heart L-alanine transaminase by L-propargylglycine. Half-site reactivity.

L-Alanine transaminase (EC 2.6.1.2) from pig heart was found to be a dimer, with a subunit molecular weight of 55,000 and one pyridoxal phosphate bound/subunit. Seven free sulfhydryl groups/subunit were detected. Isoelectric focusing revealed three species (native pI values, 5.3 to 5.5). L-Propargylglycine was found to inactivate the enzyme at 37 degrees C with a KI = 3.9 mM and an observed maximal first order rate constant, kinact = 0.26 min-1. Incorporation of 1 [14C]propargylglycine molecule/dimer leads to greater than 97% inactivation, suggesting half-site reactivity, while the unalkylated subunit is still apparently capable of processing L-alanine, L-propargylglycine, and beta-chloro-L-alanine. The minimal stoichiometric ratio necessary for inactivation was determined to be 2.7 L-propargylglycine molecules/enzyme subunit, 2.2 molecules/subunit undergoing transamination before inactivation ensues. A deuterium kinetic isotope effect of 3.5 was observed for inactivation with DL-[2-2H]propargylglycine.

Alanine Transaminase↗

[Usefulness of transaminase determination in transfusional practice].

The usefulness of determining G.O. and G.P. transaminase is examined and techniques described. Such studies take on particular importance for the selection of particular importance for the selection of donors, some with preclinical viral hepatitis.

Alanine Transaminase↗

[The role of transaminases and mitochondrial anion porters in the energetics of animals of different ages].

Aminohydroxyacetate, an inhibitor of aminotransferases, decreases the rate of oxygen consumption by 1-day-old young rats by 35% 10 min after intraperitoneal injection, whereas for 20-day-old rats, the inhibitory effect is 56%, and for adult mice, it is 83%. More prolonged exposure to aminohydroxyacetate leads to death of the animal. One-day-old rats die 90 min after the injection, 20-day-old rats die 30 min after the injection, and adult mice die 15 min after the injection. Butylmalonate (an inhibitor of mitochondrial dicarboxylate translocator) decreases the rate of energy metabolism to a lower extent, by 38% in adult mice and by 18% in 1-day-old rats. The animals generally remain alive after the exposure to this compound. 1,2,3-benzyltricarboxylate, an inhibitor of tricarboxylate transport, shows only a weak effect on energy metabolism of animals of any age. These results provide evidence that the role of the transaminase system in energy metabolism increases with age. Mechanisms underlying weak sensitivity of newborn animals to these inhibitors are discussed.

Aging↗

[A statistical epidemiological study of a possible correlation between serum transaminase levels and viral hepatic pathology markers and lichen planus orale].

The aim of the present study is to carry out a clinical-statistical research into a large number of patients suffering from oral lichen planus (LPO) and from different odontostomatologic pathologies. In both groups of patients serum transaminase values and eventual presence of hepatopathy viral markers were investigated in order to identify a possible correlation between the aforesaid parameters and LPO, considered in its various clinical forms (papular and erosive essentially). Results had showed a close association between hepatopathy and LPO, according to results of studies performed by other Italian and Spanish groups and differently from Anglo-Saxon authors: above all an increased incidence of C hepatitis in patients with lichen was observed. Furthermore our investigation is agreed in underlining the great importance to attach to erosive form of oral lichen, that seems to join to active chronic hepatitis most frequently than papular one.

Adult↗

Increased transaminases in psychiatry: a case report.

We report the case of a patient admitted to the hospital with psychiatric troubles. Soon after admission, he presented severe hepatitis of unknown origin. Careful review of the charts, transvenous liver biopsy, right heart and hepatic pressure measurements, negative toxicologic and viral screenings were highly suggestive of hypoxic hepatitis. Indeed, the patient had previously been treated for a decompensated cardiomyopathy and medications stopped prior to the current admission. Without clear clinical evidence of heart failure he presented a brief malaise two days before the increase in liver enzymes. Holter heart recording showed afterwards bouts of ventricular tachycardia. Treatment with Dobutamine and antiarrythmics led to a rapid decrease of transaminase levels and recovery in liver function. Unfortunately, he died three weeks later from his cardiomyopathy. This case illustrates the need for cardiovascular work-up in the context of hepatitis from unknown origin.

Adrenergic beta-Agonists↗

[Determination of fructose, proteins, oxalacetic and pyruvic transaminase in the seminal plasma of vasectomized patients].

Measurement of concentrations of fructose, proteins, oxalacetic and pyruvic transaminases in seminal plasma were performed in a group of 20 normal males, 30 to 40 years old, subjected to vasectomy. There were no statistically significant differences among the values obtained before and 6 months after the vasectomy. In consecuence it is concluded that bilateral occlusion of the vas deferens do not modify the androgenic function of the testis, and that certain enzymes like glutamic oxalacetic and pyruvic transminases are not incorporated to the semen by the testis but rather by the prostate and/or by the seminal vesicles.

Adult↗

[Chronic HCV hepatitis with normal level of alanine transaminase: interferon therapy of active observation?].

Patients with markers of replication of chronic HCV-infection and normal level of alanine transaminase received antiviral monotherapy with interferon. Clinical, biochemical, virological data were compared to morphometric examinations of the hepatic biopsy at different stages of interferon therapy. Relevant correlations with the controls were made. Interferon therapy in the above patients should be conducted on the individual basis.

Adult↗

Effect of varying vitamin B6 intake of early-weaned piglets on urinary xanthurenic and kynurenic acid excretion, serum transaminase activity and urea concentration.

In a bipartite rearing experiment (day 1-24 and 24-45) 72 early-weaned piglets were used to study the effect of varying dietary vitamin B6 contents on renal excretion of xanthurenic and kynurenic acid after a tryptophan load, on urea concentration and activities of two transaminases in serum at the end of each period. The animals, divided into 6 groups, were fed ad libitum a prestarter and a starter in period I and II, respectively, each containing 0.5, 1.2, 2.0, 2.8, 3.5 or 6.6 mg vitamin B6 per kg dry matter. The urinary xanthurenic acid excretion was elevated especially at the vitamin B6 supply of 0.5 ppm and rose severalfold with increasing depletion time (period II). In both periods, the smallest amount was excreted by piglets supplemented with 2.8 ppm. In comparison to groups B (1.2 ppm) and C (2.0 ppm), their average excretion rate was reduced by 29% and 15%, respectively, in period I and by 50% and 22%, respectively, in period II. Analogously to xanthurenic acid, the smallest amount of kynurenic acid was excreted by group D (2.8 ppm). Starting from the lowest vitamin B6 supply, the activity of SGPT showed an almost linear increase in both experimental periods. In contrast, SGOT already reached an upper activity level with the dietary vitamin B6 content of 3.5 and 2.8 ppm at the end of period I and II, respectively. The concentration of serum urea was influenced only by the lowest vitamin B6 supply of 0.5 ppm.

Alanine Transaminase↗