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PubMed1994

[Moderate rise of transaminases in asymptomatic patients. An etiologic approach from the primary care viewpoint].

OBJECTIVE: To discover the frequency of presentation, the aetiological distribution and clinical importance of a moderate rise in transaminases, which were found by chance in patients free from hepatic symptomology who were attending primary care clinics. DESIGN: Descriptive study of a crossover type. SETTING: La Victoria Health Centre in Valladolid. PATIENTS: The patients attended at any of the six general medical clinics between january and june 1993, in whom a moderate rise in transaminases was detected by chance and confirmed after a one-month interval. MEASUREMENTS AND MAIN RESULTS: Hepatic function tests were performed on 1,285 patients, in 212 of whom biochemical function was found to be disturbed. 137 of these 212 were studied in line with a diagnostic procedure worked out in collaboration with the Area specialist, after 75 had been eliminated for various reasons. The following aetiological distribution was observed: Viral 37.2% (Anti VHC + 30.7%, Ag HBs + 6.5%), ethylic 35.03%, metabolic 15.32% and medicinal 8.77%. Hemochromatosis was diagnosed in 2 patients; and a possible aetiology could not be established in 3. It was possible to perform a biopsy on 11 patients, with the suspected aetiology being confirmed in all of them. CONCLUSIONS: The likelihood of the primary care doctor correctly diagnosing hepatic illnesses is high, given that we could establish an aetiology in 97% of cases. The most common aetiologies were viral and ethylic.

Adult↗
PubMedDate not supplied

[Functional interrelationships between dehydrogenases and transaminases in various regions of the rat brain as affected by small doses of gamma-radiation].

Wistar rats were exposed to 10, 20 and 40 sGy of gamma-irradiation. Maximal activity of 2-oxoglutarate- and succinate dehydrogenases, as well as of aspartate-2-oxoglutarate and pyruvate-2-oxoglutarate in the brain tissue was measured within 30 days after the exposure. Dehydrogenase activity was measured in the brain cortex, limbic system and in the cerebellum; transaminase activity was determined in the brain cortex, diencephalic zone and in the hypophysis. It was found that small doses of irradiation resulted in an oscillating increase of dehydrogenase activity with a decrease of the amplitude by the 30th day of the experiment. As the dose of irradiation increases, the periods of normal activity change into phases of inhibition of dehydrogenase action, the period of oscillations diminishes. Transaminase activity, as a rule, changes in a phase in a reversible manner as compared with dehydrogenase activity. These observations are discussed from the point of view of structural relations between these two systems in the intramitochondrial supramolecular structures, the so-called metabolons.

Alanine Transaminase↗
PubMed1975

Isolation and characterization of tryptophan transaminase and indolepyruvate C-methyltransferase. Enzymes involved in indolmycin biosynthesis in Streptomyces griseus.

Two enzymes, tryptophan transaminase and indolepyruvate C-methyltransferase, which are active in the initial steps of the biosynthetic pathway of the antibiotic indolmycin, have been detected and partially purified from cell-free extracts of Streptomyces griseus. The transaminase has been purified 3-fold by ammonium sulfate fractionation. At this stage of purification, it catalyzes the alpha-ketoglutarate and pyridoxal phosphate-dependent transamination of L-tryptophan, 3-methyltryptophan, L-pphenylalanine, and L-tyrosine. The C-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to position 3 of the aliphatic side chain of indolepyruvate. No cofactors are required. The C-methyltransferase has been purified 110-fold by ammonium sulfate fractionation, Sephadex G-150 gel filtration, DEAE-Sephadex column chromotography, and Bio-Gel A-5m gel filtration. The enzyme has a broad pH optimum of 7.5 to 8.5. A molecular weight of 55,000 +/- 5,000 has been determined by Sephadex G-200 gel filtration with reference proteins and a molecular weight of 58,000 +/- 8,000 has been determined by sucrose density gradient centrifugation. The enzyme is relatively stable at temperatures of 0-5 degrees but is destroyed by freezing or by heating. The C-methyltransferase is inhibited strongly by the thiol reagents p-chloromercuribenzoate and N-ethylmaleimide. The Zn2+ and Fe2+ chelators 1,10-phenanthroline and 2,2'-bipyridine also inhibit the enzyme activity but EDTA does not. Michaelis-Menten constants have been determined for the 110-fold purified enzyme as 1.2 X 10(-5) M for S-adenosylmethionine and 4.8 X 10(-6) M for indolepyruvate. The enzyme activity in the crude extract is inhibited competitively by indolmycin (Ki equals 2.3 mM) and L-tryptophan (Ki equals 0.17 mM), but these effects are not observed after the enzyme has been passed through the Sephades G-150 column during purification. The crude extract is capable of methylating phenylpyruvate and p-hydroxyphenylpyruvate but this capability is lost upon purification of the indolepyruvate C-methyltransferase activity. No methylation of L-tryptophan occurs under the conditions used.

Anti-Bacterial Agents↗
PubMed1994

Ultrastructure of human liver grafts preserved with UW solution. Comparison between patients with low and high postoperative transaminases levels.

We studied the morphology of sinusoidal cells on 21 human liver grafts prior to harvesting, at the end of the preservation period in UW solution, and after complete revascularization. The mean cold ischemic period was 11 h 34 min. Immediate follow-up was uneventful in 20 of these cases; 13 showed a mean peak of postoperative transaminases below 1,300 IU/L (group A), and 7 above 1,500 IU/L (group B). In the case of one patient (group C) steatosis was severe (50%) and there was serious postoperative dysfunction (transaminases 18,000 IU/L). Biopsies were perfusion-fixed by the transparenchymal route to ensure satisfactory ultrastructural results. In group A, some sinusoidal endothelial cells presented signs of activation at the end of the preservation period, and even more after revascularization. Kupffer cells also presented signs of activation particularly after reperfusion. Signs of endothelial cell damage with gaps and partial rupture of the plasmic membrane were also observed, particularly after revascularization in areas which contained numerous inflammatory cells adhering to the wall. The sinusoidal pole of hepatocytes was occasionally damaged, with the formation of blebs. In group B, adhesion of inflammatory cells to the sinusoidal wall was increased. Furthermore, in some areas with endothelial cell damage, neutrophils and platelets infiltrated the Disse space, and hepatocytes were increasingly damaged. In the case of patient C, the most obvious signs after reperfusion were hepatocyte drop out and death but there was no evidence of any concomitant sinusoidal cell damage. It would appear that even in cases where immediate follow-up is eventful, endothelial and Kupffer cells show signs of activation. This can be associated with signs of microcirculatory disturbances as was seen in 4 cases in group B. In the only case of severe steatosis that we studied, the essential sign was death of hepatocytes.

Adenosine↗
PubMed1993

Increased alanine transaminase activity associated with tetracycline administration in a cat.

Administration of tetracycline was believed to be associated with an adverse drug reaction in a cat. Clinical signs consisted of anorexia, ptyalism, and signs of depression. The most noticeable biochemical abnormality was a markedly high serum alanine transaminase activity. Treatment consisted of vitamin E and selenium injections and feeding via a gastrostomy tube. Abnormalities noticed on histologic examination of hepatic tissue were centrilobular fibrosis, mild diffuse cholangiohepatitis, and mild hepatic lipidosis. The lipidosis was believed to have resulted from tetracycline administration, whereas the more chronic lesions (hepatic fibrosis and mild cholangiohepatitis) were believed to have resulted from preexisting, subclinical hepatic disease. Because serum alanine transaminase activity returned to reference ranges and the anorexia and ptyalism resolved with cessation of tetracycline administration, these abnormalities were believed to have represented an adverse drug reaction. Treatment of the cat with vitamin E and selenium was instituted on the basis of reported preventive and therapeutic effects in albino rats with tetracycline-induced hepatic lesions. Whether these compounds had any role in accelerating clinical recovery in this cat is uncertain.

Alanine Transaminase↗
PubMed1996

Genetic analysis of serum alanine transaminase activity in normal and hepatitis C virus-infected chimpanzees: an application of research-oriented genetic management.

The hepatic enzyme alanine transaminase (ALT) is a diagnostic marker for liver damage but has a considerable degree of normal variation. We used complex segregation analysis to determine whether evidence exists for major genic determination of normal ALT values in an important animal model, the chimpanzee (Pan troglodytes). Normal ALT values were available for 212 chimpanzees. Available genealogical data allowed assignment of 165 animals to a total of 19 pedigrees; 47 animals were treated as independent. A major gene explaining 60% of the phenotypic variance in normal alanine transaminase (ALT) activity was detected by complex segregation analysis. The allele for high ALT activity had a frequency of 0.20. Polygenes accounted for an additional 20% of the variation. The observation that 80% of the total phenotypic variance is attributable to genetic factors has important implications for studies that use ALT activity in assessments. Genetic analysis of change in ALT activity after inoculation with hepatitis C virus (HCV) in a subset of animals indicated that approximately 30% of the variation in response may also be attributable to genetic factors and that the estimated major locus genotypes differ in their responses. This suggests that genetic components can exert substantial influences on experimental parameters in hepatitis research.

Alanine Transaminase↗
PubMed1997

Persistent transaminase elevation due to heterozygous (familial) apolipoprotein B deficiency.

Homozygous apolipoprotein B deficiency can present with fatty liver and raised levels of transaminases. Subjects with heterozygous deficiency are almost always asymptomatic. We report an asymptomatic 26-year-old man with persistently raised transaminases, in whom the diagnosis of heterozygous (familial) apolipoprotein B deficiency was made on the basis of characteristic lipid profile.

Adult↗
PubMed1997

[A hypothesis on the significance of an increase in serum transaminases in patients with hydatidosis treated with benzimidazole carbamates].

Increase of aminotransferases was observed in 58 out of 448 patients with hydatid disease without other risk factors (28 males and 30 females) during treatment with mebendazole and albendazole; all these patients had liver cysts. The enzymatic increase was always reversible and slight (ranged from 2-4 folds the normal values in most of patients), even without stopping treatment; it was less frequently observed during further cycles of therapy and it was never observed after surgical asportation of the cysts. Jaundice was never observed. The increase of transaminases appeared to be significantly correlated to effectiveness of therapy and to the earlier occurrence of degenerative modifications of the hydatid cysts. The authors hypothesize that besides hepatoxicity (in cases of marked increase of aminotransferases or in patients without liver cysts) slight increase of transaminases could be due to pericystic inflammation secondary to the marked host's immunitary reaction, and so could be considered as an index of therapeutic effectiveness.

Adolescent↗
PubMed1997

Activities of superoxide dismutase and catalase in erythrocytes and transaminases in the plasma of carps (Cyprinus carpio L.) exposed to cadmium.

Total superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) activities in erythrocytes and the glutamic acid-oxalacetic acid-transaminase (GOT, EC 2.6.1.1) and glutamic acid-pyruvic acid-transaminase (GPT, EC 2.6.1.2) activities in the plasma were measured in experimental groups of carps (Cyprinus carpio L.) exposed to cadmium in a concentration of 20 mg Cd/l water under aquarium conditions for 6, 12, 18 and 24 hours and in control fishes. It was shown that the total activity of SOD in the erythrocytes is significantly decreased after 12, 18 and 24 hours of cadmium exposure. Increased activities of CAT (after 24 hours) in the erythrocytes and GOT and GPT in the plasma were found in cadmium-treated fishes. At the same time the concentration of blood haemoglobin and haematocrit values were significantly diminished. These results indicate that cadmium causes oxidative stress and tissue damage in the exposed fishes.

Alanine Transaminase↗
PubMedDate not supplied

Long-term follow-up of hepatitis B virus carriers with normal transaminases levels.

There has been very little data recorded on the natural course of chronic hepatitis B virus infection in asymptomatic children. In order to assess the natural course of liver disease in hepatitis B surface antigen (HBsAg) carriers with normal liver tests, 124 such children (81 males, 65.3%) were followed for six to 144 months (mean 36.8 +/- 22.8 months). Liver tests and hepatitis B virus (HBV) markers were tested at least every six months. In the beginning, hepatitis B e antigen (HBeAg) was positive in 61 (53%) of the 115 carriers of HBsAg who were tested. Anti-HBe was positive in 51 (44.3%), and both HBeAg antigen and anti-HBe were negative in three (2.7%) carriers. The prevalence of HBeAg was not affected by the patient's age or sex. During follow-up, 11 patients (18%) lost HBeAg (a mean annual clearance rate of 5.8%), and 12 patients (9.7%) lost HBsAg (a mean annual clearance rate of 3.1%). We found no difference in the clearance of HBsAg and HBeAg by age and sex. The presence of another HBsAg positive person in the family affected HBsAg clearance rate but not HBeAg clearance. Only seven patients (5 HBeAg positive and 2 anti-HBe positive) developed transient elevations in liver transaminases. Three of five HBeAg positive children cleared HBeAg after transaminases elevations. Of the five patients who underwent percutaneous liver biopsies, non-specific changes were found. It is concluded that hepatitis B carriers with normal liver tests should be followed with liver function tests alone and that long-term prognosis is good.

Carrier State↗
PubMed1975

Synteny between the pro+ marker and human glutamate oxaloacetate transaminase.

Chinese hamster ovary cells with a specific auxotrophy for proline were fused with human cells from a variety of sources and the resulting hybrids analyzed for human genetic markers. Of 63 hybrid clones examined, 27 possessed both proline and cytoplasmic glutamate oxaloacetate transaminase markers; 36 had neither; and no clones were found possessing one and not the other. These results constitute evidence that the proline and glutamate oxalocetate transaminase markers are syntenic. Evidence for absence of synteny between these and a variety of other human genes is presented. Biochemical tracer experiments established that the proline biosynthetic pathway through glutamate has been restored in the Pro+ hybrids.

Animals↗
PubMed1976

Assignment of the gene for cytoplasmic glutamic-oxaloacetic transaminase to the region q-24-qter of human chromosome 10.

Somatic cell hybrids between thymidine kinase-deficient mouse cells and human fibroblasts carrying a translocation of the distal third of the long arm of chromosome 10 to chromosome 17 were studied for the expression of cytoplasmic glutamic-oxaloacetic transaminase. A positive correlation between the expression of human cytoplasmic glutamic-oxaloacetic transaminase and the presence of the distal third of the long arm of chromosome 10 was established.

Aspartate Aminotransferases↗
PubMed1991

A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level.

Pyridoxal 5'-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C alpha of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-alpha-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.

Amino Acid Sequence↗
PubMed1978

Clinical significance of mitochondrial glutamic-oxaloacetic transaminase in serum of patients with liver disease.

Serum mitochondrial glutamic-oxaloacetic transaminase activity was determined in 83 patients with various liver diseases and 10 healthy adults. 1) The average of mitochondrial glutamic-oxaloacetic transaminase value was 1.2 mU in healthy adults, 8.3 mU in patients with acute hepatitis, 13.7 mU in patients with post-transfusion hepatitis, 5.0 mU in patients with persistent hepatitis, 4.5 mU in patients with chronic inactive hepatitis, 9.6 mU in patients with chronic active hepatitis, 5.6 mU in liver cirrhosis, and 295 mU in a patient with fulminant hepatitis. 2) While one patient with acute hepatitis showed the highest value in the group of 29 mU, one patient with fulminant hepatitis showed an extremely high value of 295 mU, revealing an obvious difference between them. 3) One patient with fresh myocardial infarction also showed an extremely high value of 110 mU.

Antibodies↗
PubMed1981

Reorientations of coenzyme in aspartate transaminase studied on single crystals of the enzyme by polarized-light spectrophotometry.

Investigation of polarized-light absorption spectra of single crystals of cytosolic aspartate transaminase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) from chicken heart has revealed that the coenzyme's absorption bands at 430 and 360 nm are polarized in opposite directions, both in crystals of the free enzyme and in its complex with a quasi-substrate, 2-methylaspartate. The opposite signs of polarization of the 430 and 360 nm bands of the free enzyme indicate different orientation of the pyridine ring of pyridoxal 5'-phosphate in the protonated and non-protonated forms of the "internal" coenzyme-lysine aldimine. These data suggest that reorientation of the coenzyme ring occurs mainly in the first step of the catalytic reaction, associated with proton transfer from the NH+3 group of amino acid substrate to the coenzyme-lysine aldimine. Absorption bands at 333 and 430 nm are seen in the spectra upon soaking the crystals in solutions containing aspartate, glutamate or cysteinesulfinate. Both bands are polarized in the same direction as is the 430 nm absorption bands of the protonated internal aldimine. Soaking the crystals in solutions containing 2-oxoglutarate, glutarate or maleate reverses the sign of polarization of the 430 nm band. High concentrations of acetate induce the same effect. Thus, binding of dicarboxylate or acetate anions in the active site of aspartate transaminase appears to result in partial or complete return of the coenzyme ring to a position similar to that of the non-protonated internal aldimine.

Acetates↗
PubMed1975

Activation by pyridoxal 5-phosphate of aspartate transaminase in serum of patients with heart and liver disease.

When aspartate transaminase activity in serum is increased, pyridoxal 5-phosphate addition produces more pronounced activation of post-myocardial infarct sera than of sera from patients with chronic liver disease. Possible explanations for this are considered. Routine pre-incubation of sera with pyridoxal phosphate prior to aspartate transaminase determination is recommended.

Aspartate Aminotransferases↗
PubMed1988

Glutathione S-transferase levels in autoimmune chronic active hepatitis: a more sensitive index of hepatocellular damage than aspartate transaminase.

Glutathione S-transferase (GST; EC 2.5.1.18), a sensitive marker of hepatocellular damage, was measured in patients on therapy for histologically proven, autoimmune chronic active hepatitis at various stages of the disease. GST levels were elevated in 65% of serum samples despite immuno-suppressive treatment compared with aspartate transaminase (AST) which was increased in only 23% of samples. In 55% of samples with normal AST concentrations, GST was elevated. No samples demonstrated abnormal transaminase with normal GST levels. It is concluded that continuing hepatocellular damage occurs in patients with autoimmune chronic active hepatitis on immuno-suppressive treatment.

Adolescent↗