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At least 595 records · Page 33Linked to original sources
PubMed1979

[Increased transaminase activity in the patients and personnel of dialysis centers and problem of its assessment].

Within the general hepatitis prevention on dialysis wards regular controls of the liver values and the HBsAG/AK are necessary for the patients and the personnel. The general symptom which is frequently found in these cases -- increased transaminase -- demands a diagnostic clarification and the exclusion of an acute virus hepatitis. Using all examination methods which are at present at our disposal and taking into consideration epidemiologic criteria and the total clinical picture a decision must be done which is right for the patient and the entire dialysis personnel. Own clinical observations refer to the fact that isolated increases of the liver enzyme in dialysis patients must not be traced back a priori to a virus hepatitis, but that these may also be caused by other endogenic and exogenic noxae. In the observation period of 10 years was evident that in an existing infectious hepatitis the increase of the liver enzyme was accompanied by clinical complaints.

Alanine Transaminase↗
PubMed1979

Hypersynchronisation and sedation produced by GABA-transaminase inhibitors and picrotoxin: does GABA participate in sleep control?

Systemic administration of GABA-transaminase inhibitors, gamma-acetylenic GABA (100 mg/kg) or gamma-vanylic GABA (1200 mg/kg) produces behavioral picture of somnolence accompanied by EEG hypersynchronisation reminiscent of electrographic signs of petit mal epilepsy. Similarly, systemic administration of GABA antagonist, Picrotoxin (3--4 mg/kg) produces a short lasting period of sedation preceding the development of myoclonic jerks which is also accompanied by Wave-spike discharges. The role of GABA in sleep control is discussed. Although the area is not ready for firm conclusions, the results suggest that hyperactivity of GABA-ergic system as well as its hypoactivity could mediate pathological somnolence associated with different forms of epilepsy.

4-Aminobutyrate Transaminase↗
PubMed1978

Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina is a chorioretinal degeneration associated with hyperornithinemia with an autosomal recessive mode of inheritance. Cultured skin fibroblasts from five affected patients showed a virtual absence of ornithine ketoacid transaminase (OKT) (L-ornithine:2-oxoacid aminotransferase E.C.2.6.1.13) activity. Fibroblasts from four carrier parents showed a 42%-65% reduction in OKT activity. Increasing the concentration of pyridoxal phosphate (vitamin B6 in the assay media resulted in partial restoration of OKT activity in fibroblasts from one out of five patients studied. We conclude that OKT deficiency is closely associated with the genetic defect in gyrate atrophy of the choroid and retina and that genetic heterogeneity exists in this disease.

Adolescent↗
PubMedDate not supplied

[Effect of early visual deprivation on GABA transaminase activity in the brain structures of dogs].

Activity of GABA-transaminase was distinctly decreased as compared with controls in all the brain structures studied in animals growing under conditions of early visual deprivation. At the same time, alterations were developed in synthesis of glutamic and aspartic acids and in their ratio. Biosynthesis of glutamic acid was decreased 2-fold in parietal cortex region and in cerebellum of 45 day-old animals, less distinct decrease in the amino acid synthesis was observed in the locomotion brain region of the animals as compared with controls. At an age of 90 days, to the contrary, most distinct decrease (3-fold) in glutamic acid synthesis occurred in the locomotion region and a less distinct decrease - in cerebellum. Synthesis of aspartic acid was less distinctly altered in the deprived animals; it was decreased in cerebellum of both age groups of animals, in parietal cortex region - only in the group of 90 day-old animals and unaltered - in locomotion region of both animal groups. The values of the glutamic/aspartic acid ratio were also decreased. The pattern was quite similar in all the brain structures studied of 45 day-old animals; in the 90 day-old animals the corresponding ratios of the amino acids were increased in cerebellum, only slightly increased - in locomotion region of brain cortex and they were decreased in parietal cortex region.

4-Aminobutyrate Transaminase↗
PubMed1976

[Effect of an irreversible inhibitor (RMI71645) of gamma-aminobutyric acid (GABA) transaminase on spontaneous and conditioned activities of mice].

The RMI, an irreversible inhibitor of GABA transaminase, inhibited, at the dose of 100 mg/kg, the activity of Mice placed in an open-field. At lower doses, RMI improved the activity in open-field and the number of conditioned avoidance reactions. Results are correlated with increase of the level of brain GABA, following administration of RMI.

4-Aminobutyrate Transaminase↗
PubMed1993

Role reversal for substrates and inhibitors. Slow inactivation of D-amino acid transaminase by its normal substrates and protection by inhibitors.

D-Amino acid transaminase, which catalyzes the synthesis of D-alanine and D-glutamate for the bacterial cell wall, is a candidate for the design of specific inhibitors that could be novel antimicrobial agents. Under the experimental conditions usually employed for enzyme assays, kinetic parameters for its substrates were determined for short incubation periods, when intermediates and products do not accumulate and the enzyme activity is linear with time. Such kinetic analyses indicate that the enzyme accepts most D-amino acids but D-aspartate and D-glutamate are the best substrates. Under a different type of experimental conditions when the enzyme is exposed to D-alanine, intermediates, and products for periods of hours, it slowly becomes inactivated (Martinez del Pozo, A., Yoshimura, T., Bhatia, M. B., Futaki, S., and Manning, J. M. (1992) Biochemistry 31, 6018-6023). We now report that D-aspartate, D-glutamate, and L-alanine also lead to slow inactivation. Methylation or amidation of the alpha-COOH group of D-alanine prevents inactivation, indicating that decarboxylation is required for inactivation; the slow release of CO2 from substrate is demonstrated. The alpha-methyl analog of D-alanine, D-aspartate, and D-glutamate do not lead to inactivation, showing that the alpha-hydrogen of the substrate is required, i.e. that some processing is required. Lys145, which binds pyridoxal 5'-phosphate in the wild-type enzyme, is not involved in the inactivation since two active site mutant enzymes, K145Q and K145N, are also inactivated. Reactivation of the inactive enzyme at acidic pH is accompanied by the release of ammonia corresponding to 1 mol/mol of dimeric enzyme. Competitive inhibitors, amine-containing buffers, and thiols effectively impede the inactivation. This reversal in the roles of substrates and inhibitors, i.e. when a substrate can be an inactivator and an inhibitor can act as a protector, occurs during a time period not usually used to measure steady-state kinetics or initial velocities of enzyme reactions and could have physiological relevance in cells.

Amino Acids↗
PubMed1976

[Interaction of 4-aminobutyrate-transaminase from swine kidneys with 5'- and 6'-methyl derivatives of pyridoxal-5'-phosphate].

The study of interaction of 4-aminobutyrate transaminase with 5'- 6'-methyl derivates of PLP demonstrated that only the former was capable of forming a catalytically active holoenzyme possessing 0.37 activity of the native holoenzyme and a low affinity substrates. This compound interacts with the apoenzyme at a slower rate than does PLP; it has a reduced affinity towards apotransaminase (Km = 1.10(-4) M) and is replaced from the active site by native coenzyme. The other analog of pyridoxal-5'-phosphate forms a catalytically inactive complex with the apoenzyme; the other analog is not replaced from the active center by native coenzyme and non-competitively inhibits the reconstruction of apotransaminase (Ki = 2.10(-5) M).

4-Aminobutyrate Transaminase↗
PubMed1988

Elevated serum transaminase activity at diagnosis is associated with rapidly progressing disease in children with acute lymphoblastic leukemia.

The authors study whether quantitative measurement of serum glutamate pyruvate transaminase (SGPT) activity might serve as an indicator of liver involvement at diagnosis of acute lymphoblastic leukemia (ALL) and could be used as a parameter in predicting the prognosis of individual patients. The series consisted of 123 children with newly diagnosed untreated ALL. The mean follow-up time was 69 months (range, 22-140 months). The SGPT activity at diagnosis was significantly associated with the duration of event-free survival (P less than 0.0001). For the 13 patients with SGPT activity greater than 40 IU/l the 5-year event-free survival was only 9%. All 11 patients with the lowest SGPT activities (less than 8 IU/l) remain in primary remission (24 to 81 months). The relative risk of relapse or death for children with SGPT activities of less than 8 IU/l, 8-40 IU/l, and greater than 40 IU/l were 0.2 (95% confidence limits 0.09-0.45), 1, and 4.8 (2.2-10.7), respectively (P less than 0.001). The SGPT activity at diagnosis was not associated with clinically assessed liver enlargement. The authors speculate that high SGPT activities at diagnosis are associated with a rapidly progressing, fulminant form of ALL.

Alanine Transaminase↗
PubMed2004

Vigabatrin, the GABA-transaminase inhibitor, damages cone photoreceptors in rats.

Epileptic patients experienced an irreversible loss of their peripheral visual field upon treatment with vigabatrin (gamma-vinyl GABA), an inhibitor of the GABA degrading enzyme, GABA transaminase. Subsequently, central visual function was reported to also be irreversibly altered. This visual loss is associated with a decrease in the electroretinogram measurement localizing the deficit to the retina. To investigate its cellular origin, we treated rats daily with vigabatrin for 45 days. Two days after arresting this treatment, rats exhibited an irreversible decrease in the photopic electroretinogram, the flicker response, and the oscillatory potentials. These functional alterations were associated with a peripheral disorganization of the outer retina. However, photoreceptor damage was not limited to these disorganized areas, but cone inner and outer segments were severely injured in more central areas and their numbers were irreversibly decreased by 17 to 20%. Ultrastructural examination of the retina confirmed the presence of major photoreceptor damages, which were further supported by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and caspase-3 activation both indicative of photoreceptor apoptosis. This study suggests that the visual field loss in vigabatrin-treated epileptic patients may result from a sequence of events starting from cone cell injury to a more severe disorganization of the photoreceptor layer.

4-Aminobutyrate Transaminase↗
PubMed2001

Kinetic resolution of chiral amines with omega-transaminase using an enzyme-membrane reactor.

A kinetic resolution process for the production of chiral amines was developed using an enzyme-membrane reactor (EMR) and a hollow-fiber membrane contactor with (S)-specific omega-transaminases (omega-TA) from Vibrio fluvialis JS17 and Bacillus thuringiensis JS64. The substrate solution containing racemic amine and pyruvate was recirculated through the EMR and inhibitory ketone product was selectively extracted by the membrane contactor until enantiomeric excess of (R)-amine exceeded 95%. Using the reactor set-up with flat membrane reactor (10-mL working volume), kinetic resolutions of alpha-methylbenzylamine (alpha-MBA) and 1-aminotetralin (200 mM, 50 mL) were carried out. During the operation, concentration of ketone product, i.e., acetophenone or alpha-tetralone, in a substrate reservoir was maintained below 0.1 mM, suggesting efficient removal of the inhibitory ketone by the membrane contactor. After 47 and 32.5 h of operation using 5 U/mL of enzyme, 98.0 and 95.5% ee of (R)-alpha-MBA and (R)-1-aminotetralin were obtained at 49.5 and 48.8% of conversion, respectively. A hollow-fiber membrane reactor (39-mL working volume) was used for a preparative-scale kinetic resolution of 1-aminotetralin (200 mM, 1 L). After 133 h of operation, enantiomeric excess reached 95.6% and 14.3 g of (R)-1-aminotetralin was recovered (97.4% of yield). Mathematical modeling of the EMR process including the membrane contactor was performed to evaluate the effect of residence time. The simulation results suggest that residence time should be short to maintain the concentration of the ketone product in EMR sufficiently low so as to decrease conversion per cycle and, in turn, reduce the inhibition of the omega-TA activity.

Amines↗
PubMed2004

Kinetic resolution of (R,S)-sec-butylamine using omega-transaminase from Vibrio fluvialis JS17 under reduced pressure.

The kinetic resolution of (R,S) sec-butylamine with the omega-transaminase (TA) from Vibrio fluvialis JS17 was performed under reduced pressure (e.g., 150 torr) to selectively remove an inhibitory product (2-butanone). The evaporation kinetics of 2-butanone at 150 torr in the buffer solution followed the first-order rate law, and the evaporation rate constant was 2.19 1/h, and independent of pH, while the evaporation kinetics of sec-butylamine is dependent on pH. A simple mathematical model of the evaporation of sec-butylamine allowing the estimation of its concentration in the reaction media was developed. The evaporation rate constant of its free amine form and the protonated amine form were 1.00 1/h, and nearly zero, respectively. Although the optimum pH of the omega-TA activity for sec-butylamine is 9.0, the optimal pH of the enzyme reaction under reduced pressure was pH 7.0, due to the higher evaporation rate of sec-butylamine at higher pH above 7.0. Using the recombinant Escherichia coli BL21 overexpressing omega-TA, 400 mM racemic sec-butylamine was resolved successfully to 98% ee of (R)-sec-butylamine with 53% conversion at 150 torr and pH 7.0.

Butylamines↗
PubMed2006

Synthesis of enantiomerically pure trans-(1R,2R)- and cis-(1S,2R)-1-amino-2-indanol by lipase and omega-transaminase.

Syntheses of trans-(1R,2R) and cis-(1S,2R)-1-amino-2-indanol (AI) were accomplished by a series of enantioselective enzymatic reactions using lipase and transaminase (TA). Lipase catalysed enantioselective hydrolysis of 2-acetoxyindanone was employed to prepare (R)-2-hydroxy indanone (HI). trans-AI (5 mM) (de > 98%) was produced from 20 mM (R)-2- HI using omega-TA and 50 mM (S)-1-aminoindan as an amino donor in water-saturated ethyl acetate. For the production of cis-AI, the diastereomeric (2R)-AI was synthesized from (R)-2-HI using reductive amination, and the kinetic resolution was performed with omega-TA. The enantioselectivity of omega-TA for (2R)-AI was increased to 22.1 in the presence of 5% gamma-cyclodextrin. cis-AI (15.4 mM) (96% de) was obtained from 40 mM (2R)-AI using 30 mM pyruvate and omega-TA (25 mg) in 10 mL of 100 mM phosphate buffer (pH 7.0).

Indans↗
PubMed2006

Engineering aromatic L-amino acid transaminase for the asymmetric synthesis of constrained analogs of L-phenylalanine.

An enzymatic asymmetric synthesis was carried out for the preparation of enantiomerically pure L-diphenylalanine using the rationally engineered aromatic L-amino acid transaminase (eAroATEs) obtained from Enterobacter sp. BK2K-1. To rationally redesign the enzyme, structural model was constructed by the homology modeling. The structural model was experimentally validated by the site-directed mutagenesis of the predicted pyridoxal-5'-phosphate (PLP) binding site and the substrate-recognition region, and the cell-free protein synthesis of mutated enzymes. It was suggested that Arg281 and Arg375 were the key residues to recognize the distal carboxylate and alpha-carboxylate group of the substrates, respectively. The model also predicted that Tyr66 forms hydrogen bond with the phosphate moiety of PLP and interacts with the side chain attached to beta-carbon of the amino acid substrate. Among the various site-directed mutants, Y66L variant was able to synthesize L-diphenylalanine with 23% conversion yield for 10 h, whereas the wild-type AroATEs was inactive for the transamination between diphenylpyruvate and L-phenylalanine as amino acceptor and amino donor, respectively.

Amino Acids, Aromatic↗
PubMed1998

Interferon alfa treatment of HCV RNA carriers with persistently normal transaminase levels: a pilot randomized controlled study.

Most patients with serum hepatitis C virus (HCV) RNA and persistently normal alanine transaminase (ALT) levels show histological features of mild to moderately active chronic hepatitis. Some cirrhosis has also been reported. To assess whether interferon (IFN) treatment led to long-term HCV suppression in these patients, 31 previously untreated patients (15 men, 16 women; mean age, 44 years) with serum HCV RNA, persistently normal ALT levels on at least four consecutive occasions 2 months apart, and histological features of chronic hepatitis (21 mild activity, 10 moderate activity) were randomized to receive 1FN-alpha-2a, 3 MU three times a week for 6 months (n = 16), or no treatment (n = 15). All patients were followed up for at least 6 months after treatment ended. HCV RNA was tested by nested reverse-transcription polymerase chain reaction (RT-PCR) using 5'-untranslated region complementary primers, quantified by branched-DNA assay, and typed by nested RT-PCR testing for the HCV core region. Treated and untreated patients had similar epidemiological, virological, and histological characteristics. At the end of treatment, serum HCV RNA was still detected in 15 patients (94%) and 14 controls (93%). ALT levels flared up in 10 patients receiving IFN (62%) and in 1 control (62% vs. 7%; P < .005, chi2 test). In conclusion, 6 months' treatment with IFN-alpha-2a did not eradicate HCV RNA from serum in carriers with persistently normal ALT levels but caused ALT flare-ups in two thirds of them. Until more is known about the natural history of HCV RNA carriers with normal ALT levels, these patients should not be treated with IFN.

Adult↗
PubMed1998

Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity.

In hepatitis C virus (HCV) patients with persistently normal alanine transaminase (ALT), the progression rate of fibrosis is unknown. The aims of this study were: 1) to compare HCV patients with normal ALT (group I) with HCV patients with elevated ALT (group II) matched on independent factors associated with fibrosis; and 2) to assess the progression rate of fibrosis. One hundred two HCV patients were included in each group. Histological lesions were staged using the METAVIR score. We defined fibrosis progression per year as the ratio of the fibrosis stage in METAVIR units to the duration of infection. In group I, ALT values were normal, and lower than in group II (25 vs. 127 IU/L; P < .0001). HCV RNA was present less frequently in group I (66% vs. 97%; P < .0001). There were no significant differences for viremia and genotypes. Histological activities were lower in group I (0.6 vs. 1.38; P < .0001). The stage of fibrosis was lower in group I (0.95 vs. 1.8; P < .001). The median progression rate of fibrosis was lower in group I (0.05 vs. 0.13; P < .001). In group I, after exclusion of negative HCV-RNA patients, the median progression rate of positives remained lower (0.05 vs. 0.13; P < .001). In group I, all cirrhotic patients (n = 3) were heavy drinkers. HCV patients with normal ALT showed weaker histological activity and lower fibrosis scores, and the progression rate of fibrosis was twice as slow as in HCV patients with elevated ALT. In these patients, severe fibrosis was associated with high alcohol consumption.

Adolescent↗
PubMed1998

Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group.

In clinical research, the definition of the upper limit of normal (ULN) alanine transaminase (ALT) is never detailed. However, such a definition can vary and may have practical consequences. Our aim was to assess factors associated with serum ALT activity in apparently healthy subjects and then to apply seven different definitions of ULN in three different populations so as to assess the prevalence of subjects with normal ALT among blood donors and among hepatitis C patients before (normal ALT hepatitis C patients) and after treatment (interferon [IFN] responders). ALT measurements were performed in the same laboratory using the same technique; 1,033 donors were prospectively investigated, 186 patients with hepatitis C never treated and 40 patients treated with 3 MU three times per week of IFN-alpha for at least 6 months. The seven definitions (D) of ULN were: D1: 95th percentile of ALT; D2: 95th percentile after separating males and females; D3: males and females separately, ULN=10 (mean of log10 ALT + 1.96 SD); D4: ULN=45 IU/L given by the manufacturer; D5: mean + 1 SD after exclusion of the 5% extreme values; D6: 95th percentile after separating subjects with body mass index (BMI) under or equal to the median (23); and D7: 95th percentile after separating subjects according to BMI and sex. BMI and male sex were independently associated (P < .0001; logistic regression) with ALT, without an association with alcohol. The range of ULN varied from 26 IU/L in females (D5) to 66 IU/L in males with BMI >23 (D7). Depending on the definition, the prevalence of blood donors with normal ALT varied from 82% to 96%, i.e., a range of 14%; that of hepatitis C patients with normal ALT varied from 16% to 27%, i.e., a range of 11%; the prevalence of IFN responders varied from 25% to 42%, i.e., a range of 17%. Definitions of normal ALT values should be adjusted for sex and BMI to reduce artificial heterogeneity in blood donor selection and in hepatitis C clinical studies.

Adult↗
PubMed1999

Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group.

In the reported Asian lamivudine trial, the rate of hepatitis B e antigen (HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA seroclearance and development of anti-HBe, during 52 weeks of treatment was only 13% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg seroconversion with variables including treatment, age, gender, body build, histology, baseline HBV-DNA levels, and alanine transaminase (ALT) levels. Exploratory analysis using stepwise modeling revealed that HBeAg seroconversion correlated highly with pretherapy ALT (P <.001) followed by lamivudine therapy (P =.013), but only marginally with baseline HBV-DNA (P =.071) and cirrhosis (P =.066) for lamivudine 100 mg and placebo comparison. Among these four variables, only pretherapy ALT still had a highly significant (P <.001) correlation and lamivudine therapy had a borderline association (P =.066) for lamivudine 25 mg and placebo comparison. Categorical analysis revealed that HBeAg seroconversion occurred earlier and the cumulative rate was significantly higher in patients with pretherapy ALT values over 2 times the upper limit of normal (ULN) as compared with treated patients with lower ALT levels or untreated control patients with the same ALT levels (P <.001, respectively). The highest HBeAg seroconversion rate was observed in 100 mg lamivudine-treated patients with ALT levels greater than 5 times the ULN (64%) compared with patients with ALT 2 to 5 times the ULN (26%, P =.03); and ALT less than 2 times the ULN, (5%, P <.001). These results suggest that pretherapy ALT is the strongest determinant for HBeAg seroconversion during lamivudine therapy, and should be considered in selecting patients for treatment.

Alanine Transaminase↗