Effect of cofactor depletion on liver tyrosine aminotransferase expression.

Hepatic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from pyridoxine depleted and control rats and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gel. Six enzymatically active forms were detected. Cofactor depletion effected further resolution of the enzyme into seven active forms as revealed by the bifurcation of the major active peak.     

Age-related changes of liver tyrosine aminotransferase in senescent rats

Tyrosine aminotransferase was induced in adult and senescent rat liver and its properties studied. We show the appearance of a 'cross-reacting material' for induced tyrosine aminotransferase of old rats compared to basal enzyme; this cross-reacting material can be provoked in adult rats after injection of cycloheximide, and suppressed in adult and old rats after injection of a serine protease inhibitor (tosylphenylalanine chloromethylketone). Other properties of induced tyrosine aminotransferase (thermostability, Km for tyrosine, isoelectrofocusing) are identical except for the proportion of the three forms and their sensitivity to trypsin in the absence of pyridoxal phosphate, which is increased in senescent animals. The suppression of cross-reacting material clearly indicates that it is not due to errors on old rat liver DNA but rather to post-translational modifications. This demonstrates also the role of serine proteases in tyrosine aminotransferase degradation. We suggest that induced enzyme of senescent rats would undergo a conformational change, possibly due to a release of pyridoxal phosphate from the enzymic molecules, which would thus become more susceptible to proteolytic attack than those of adult rats.     

Regulation of hepatic tyrosine aminotransferase in genetically obese rats

The activities of hepatic tyrosine aminotransferase, tryptophan oxygenase and serine dehydratase were increased in obese rats shortly after weaning. Immunotitration experiments showed that the increase in tyrosine aminotransferase activity resulted from an increase in enzyme protein in obese rats. No increase in hepatic tyrosine aminotransferase was observed in suckling pre-obese rats. The post-weaning increase in hepatic tyrosine aminotransferase of obese rats was only observed during the light phase of the diurnal cycle, but was prevented by pair-feeding and by starvation. Tryptophan increased hepatic tyrosine aminotransferase of lean rats to obese levels but had no effect in obese rats until tyrosine aminotransferase levels were reduced by starvation or adrenalectomy. Adrenalectomy abolished the increase in hepatic tyrosine aminotransferase activity in obese rats although serum corticosterone was normal in these animals. Hepatic and brain tyrosine concentrations were decreased in obese rats but normalized after adrenalectomy. The results suggest that the corticosteroid-dependent increase in food and tryptophan intake may be the primary cause of the increased hepatic amino acid catabolism of obese rats.     

Receptor dynamics and tyrosine aminotransferase induction during the course of chronic treatment of rats with glucocorticoid

The changes in the cytosol glucocorticoid receptor (GR) content during a long-term administration of a glucocorticoid were studied to examine the mechanism of the development of steroid hormone resistance. Dexamethasone (Dex) (0.2 microgram/ml and 2.0 micrograms/ml) was given to adrenalectomized rats, and the GR content was determined using the exchange assay 1, 10, 20 and 50 days after the start of administration. The activity of tyrosine aminotransferase (TAT) in the cytosol was also assayed as a measure of the biological responsiveness of these animals to the administered glucocorticoid. The dissociation constant (Kd) was elevated and the Bmaxs of the GR in the cytosol were decreased by the lower concentration of Dex. The Bmaxs decreased to 30% of the untreated controls within 24 h and this lower level was maintained as long as the hormone treatment continued. On the other hand, the cytosol obtained from animals treated with 2.0 micrograms/ml of Dex for 20-24 days did not show any measurable amount of binding to 3H-Dex. The activity of TAT was elevated 24 h after the administration of Dex but decreased gradually and steadily with time during the experimental period. To examine the biological potency of remaining GR in the liver cytosol, 2.0 micrograms/ml Dex was again administered after a long-term treatment. This treatment eliminated the remaining GR completely and induced TAT at almost the same rate as observed in the untreated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ontogeny of tyrosine aminotransferase in Xenopus laevis.

The development of tyrosine aminotransferase (TAT) activity in Xenopus laevis embryos was studied. Undivided eggs can transaminate tyrosine to some extent. The enzyme activity increases after hatching on the third day of development. In the early stages of development, the transamination of tyrosine is due to aspartate aminotransferase (ASAT, EC 2.6.1.1), both isoenzymes of which are present in the undivided egg. No specific TAT (EC 2.6.1.5) can be detected until the age of about 1 day, at which time neurulation is complete and the rapid development of the foregut and visceral pouches and arches has begun. The appearance of the enzyme is immediately preceded by a steep increase in the concentration of free tyrosine. Tyrosine aminotransferase is known to be induced by its substrate in the adult liver, and a similar effect may operate in the embryo.     

Characterization of liver tyrosine aminotransferase in rats using an immunoaffinity technic

Antisera directed against synthetic peptides with sequences that correspond to selected regions of tyrosine aminotransferase may react with the protein without affecting its biological activity. The antiserum against the theoretical N-terminal dodecapeptide recognizes the enzyme and makes it possible to detect a blocked form of the enzyme. Another form shortened by seven aminoacids and starting with Thr 8 has been found. The isolation of tyrosine aminotransferase by one step affinity chromatography is now made possible; nevertheless the elution procedure remains a critical point. The strategy described should have further applications and allow the detailed exploration of the essential domains of aminotransferases, especially those involved in the function and the degradation of pyridoxal phosphate requiring enzymes.     

Correlation of circadian changes in tyrosine aminotransferase and tryptophan-2-3-dioxygenase in rat liver to irradiation at different times of the day

Male SPF Wistar rats adapted to a 12:12 h light: dark regimen were irradiated at 3-hour intervals in the course of 24 h with a dose of 14.35 Gy X-rays; 24 h after irradiation or sham irradiation and starvation for the same length of time, and also in fed intact rats, tyrosine aminotransferase and tryptophan-2-3-dioxygenase activity in the liver and the serum corticosterone level were determined. Although lethal irradiation modified the given enzyme activities, it did not abolish their circadian rhythm, evidently in association with the low sensitivity in association with the low sensitivity of the liver to ionizing radiation. In irradiated animals (compared with sham-irradiated animals), the serum corticosterone concentration fell during the light part of the day and at the beginning of the dark part.     

Activation of tyrosine aminotransferase expression in fetal liver by 5-azacytidine

Rat fetuses of 20 days gestational age were treated in utero with the inhibitor of DNA methylation, 5-azacytidine. The liver enzyme tyrosine aminotransferase, normally expressed at very low levels until several hours after birth, was increased by the drug in the fetal livers after a lag period of about 9 hours, reaching a level 70-fold above control levels 18 hours after treatment. The high levels attained after 5-azacytidine treatment are comparable to those of glucocorticoid-treated adult livers, and were not further increased by administration of hydrocortisone to dams carrying treated fetuses. Cytidine and two other analogs, cytosine arabinoside and 6-azacytidine, were essentially without effect.     

Dynamic asymmetries in liver tyrosine aminotransferase induction.

Changes in liver tyrosine aminotransferase activity were measured in mice and rats following a whole body X-irradiation in order to ascertain the dose-effect relationship. The response was either (1) linear in case of low pulses (25 rad/min); (2) parabolic, indicating the onset of a saturation process in case of medium pulses (60 rad/min), or (3) biphasic, suggesting the cooperation of at least two regulatory mechanisms following longtime exposure to strong stimuli (100 rad/min).     

Kynurenine aminotransferase and alpha-aminoadipate aminotransferase: III. Evidence for identity with halogenated tyrosine aminotransferase.

A nearly homogeneous preparation of α-aminoadipate (kynurenine) aminotransferase exhibited substantial activity with 3,5-diiodo-L-tyrosine, a major substrate for halogenated tyrosine aminotransferase. The new activity was found, according to heat inactivation and several inhibition studies, not to be attributable to contamination. Many of the properties previously reported for the two enzymes are identical or very similar. This paper lists these similarities and reports our observations of additional similarities of these activities in the supernatant and mitochondrial fractions of both rat kidney and liver. The properties of the purified enzyme and the noted similarities suggest that α-aminoadipate aminotransferase, kynurenine aminotransferase, and halogenated tyrosine aminotransferase activities are associated with the same protein. These activities are discussed in terms of a possible role in thyroid hormone metabolism.     

Tissue-specific differential induction of ornithine aminotransferase by estradiol in rats of various ages

The level and induction of ornithine aminotransferase of the liver and kidney cortex were determined at different phases of the life span of female rats. The level of this enzyme in the liver did not change significantly till adulthood and decreased thereafter. However, there was no significant differences in the level of this enzyme in the kidney cortex of the rat throughout its life span. Further, the level of this enzyme in the kidney cortex was more than 2.5-fold higher than that of the liver in all the age groups. Ovariectomy decreased, and 17-beta-estradiol increased significantly, the activity of the kidney cortex enzyme in rats except for the old ones. The effects of both these treatments were highest in the young-adult (13-weeks) rats. In contrast, the liver enzyme was irresponsive towards both these treatments.     

Hepatocyte differentiation in culture. Appearance of tyrosine aminotransferase.

Liver of rat foetuses from 14 to 19 days of gestation and cultured hepatocytes derived from foetuses of 14 or 15 days gestation show a limited capacity to transaminate tyrosine. This low tyrosine transamination activity can be ascribed to aspartate aminotransferase. Definitive tyrosine aminotransferase can be demonstrated in 1-day-old cultures of hepatocytes taken from 19-day foetuses, but not from 15-day foetuses. However, after 3 days of culture hepatocytes from 15-day foetuses are able to synthesize tyrosine aminotransferase. Induction studies reveal that dexamethasone is capable of increasing tyrosine aminotransferase activity once it is detectable in culture.     

Different expression of tyrosine aminotransferase and serine deydratase in rat livers after partial hepatectomy.

Tyrosine aminotransferase activity in rat liver increases during the first 24 hrs after partial hepatectomy with two peaks, one at 10 hrs and another at 18 hrs. This behaviour is due to an increase in TATmRNA synthesis. Expression of serine deydratase is also enhanced during the first 5 hrs after hepatectomy. It is suggested that the enhanced expression of the two genes is due to an increase in hormone incretion particularly glucagon and glucocorticoids.