Hepatic Aminotransferase Activity Research Articles

Central neural regulation by adrenergic nerves of the daily rhythm in hepatic tyrosine transaminase activity.

1. In adrenalectomized fasted rats transection of the spinal cord at C7-C8 or placement of bilateral electrolytic lesions in the lateral hypothalamus when performed in the morning interrupted the daily rhythm of hepatic tyrosine transaminase by elevating low (AM) enzyme activities to high (PM) levels; lesions placed in PM did not affect the late afternoon rise in enzyme activity.2. Bilateral thalamic lesions had no affect on enzyme activity.3. The activity of hepatic catechol-O-methyl transferase was unaffected by hypothalamic lesions.4. The lesion-evoked rise of tyrosine transaminase activity was abolished by exogenously administered norepinephrine.5. Cycloheximide blocked the rise of tyrosine transaminase activity caused by hypothalamic lesions.6. The results suggest that rhythmic activity of sympathetic nerves governed by lateral hypothalamus contribute to regulation of the daily rhythm in tyrosine transaminase by regulating the release of norepinephrine peripherally; norepinephrine may block the daily rise of enzyme by interfering with protein synthesis, possibly of new enzyme, by competing with pyridoxal co-factor.7. It is proposed that alternating activity of sympathetic-adrenergic and vagal-cholinergic nerves to liver, controlled by the C.N.S., contribute to rhythmic activity of hepatic tyrosine transaminase.

Adrenocortical influences on the development of the diurnal rhythm in hepatic tyrosine transaminase.

In the adult rat, liver tyrosine transaminase shows a characteristic diurnal pattern with a peak at 10 PM and a nadir at 10 AM. Infant rats have an inverted pattern with a minimum at 10 PM and a maximum at 10 AM until approximately 21 days of age, when the pattern flattens before changing to the adult form. To determine whether corticoids were essential for the initiation of the adult daily rhythm in liver tyrosine transaminase, rats were adrenalectomized before (16 days of age) and after (21 days of age) the onset of the diurnal variation in circulating corticosterone. Transaminase levels were determined in adulthood. Both groups exhibited the adult rhythm in liver tyrosine transaminase at 55-60 days of age. However, rats adrenalectomized at 16 days of age and sacrificed at 26 days of age still showed the immature rhythm. Drastic alterations of the maternal feeding schedule result in some shift in the infant transaminase cycle. However, adrenalectomized infants maintained with mothers given an ad lib. diet show an abrupt reversal of feeding pattern between day 16-17 and day 22-23 without alteration of the immature rhythm of hepatic tyrosine aminotransferase. The results thus demonstrate that adrenal corticoids are unnecessary for the development of the adult daily cycle although they appear to hasten its maturation into the adult pattern. They further indicate that, although the feeding schedule influences the phasing of the circadian rhythm, it does not wholly account for the inverted rhythm in the infant. (Endocrinology 89 : 936, 1971) S studies (1-3) have reported that diurnal changes in liver tyrosine transaminase in the adult rat persist despite adrenalectomy, although the peak of enzymatic activity is reduced by such endocrinopathy. These data thus indicate that endogenous daily changes in circulating levels of corticoids are unnecessary for the maintenance of the circadian rhythm in tyrosine transaminase in the adult. The development of the rhythms of both adrenal steroids and liver tyrosine transaminase also has been studied. Honova et al. (4) found periodicity in rat hepatic tyrosine transaminase activity as early as 48 hr after birth. Enzyme activity was maximal at 10 AM and minimal at 10 PM. This pattern is inverted from the adult's pattern, where the highest levels of tyrosine transaminase occur at 10 PM. The transition from the immature to the adult cycle occurs between 21 and 23 days of age. The plasma levels of corticosterone do not undergo a diurnal variation in the very young rat (5), but Ader (6) has reported that this rhythm is present at 21-25 days of age. Thus, in Received March 24, 1971. This study was supported by USPHS Research Grant AM 08775. 1 USPHS Postdoctoral Fellow (2-F-2-AM-31,47702), 1968. the rat at least, the circadian rhythm in plasma corticosterone develops either before or simultaneously with the adult daily variation in liver tyrosine transaminase. The possibility existed that, while adrenal hormones were not necessary for the maintenance of the tyrosine transaminase rhy tlim, they may be necessary for the development of the transaminase rhythm or for its normal maturation to the adult form. It has also been demonstrated that the feeding pattern influences tyrosine aminotransferase activity and this may account for the inverted form of the infant rhythm in that infants may feed during periods between maternal feedings (4). Further, adrenalectomy might also alter the feeding pattern and thereby account for the attenuated rhythm in the adrenalectomized adult. Thus, in the adult, an ad lib. diet is accompanied by liver tyrosine transaminase levels which fall to a nadir in the morning, rise in the late afternoon, and peak about 4 hr after the onset of darkness (2). If food consumption is restricted to the morning hours, the peak in hepatic enzyme activity advances to 11 AM (7). The daily rhythm is abolished if the diet lacks protein or is deficient in the amino acid tryptophan (8), and is markedly attenuated if the total daily food intake is dispersed equally throughout the day

Induction and activation of cysteine oxidase of rat liver: I. The effects of cysteine, hydrocortisone and nicotinamide injection on hepatic cysteine oxidase and tyrosine transaminase activities of intact and adrenalectomized rats

1. 1. The greatest increase in hepatic cysteine oxidase activity was observed in intact rats which received cysteine, but the increase in tyrosine transaminase activity mediated by cysteine was only one-half of that produced with nicotinamide or hydrocortisone. 2. 2. The decline of the elevated enzymic activity of either cysteine oxidase or tyrosine transaminase was delayed when these enzymes were induced by nicotinamide in intact rats. 3. 3. An additive increase in cystein oxidase activity in the intact rat was obtained by the simultaneous injection of nicotinamide with cysteine and of nicotinamide with hydrocortisone but not of cysteine with hydrocortisone. 4. 4. Hepatic cysteine oxidase and tyrosine transaminase activities in adrenalectomized rats were significantly increased after injection of hydrocortisone but not by cystein. Nicotinamide did produce a marked increase in tyrosine transaminase activity in adrenalectomized rats, while cysteine oxidase activity did not increase with either nicotinamide or cysteine. The hydrocortisone-mediated induction of hepatic cysteine oxidase activity was markedly enhanced by simultaneous injection of cysteine, but in the case of hepatic tyrosine transaminase activity, the hydrocortisone-mediated induction was not affected by cysteine injection. 5. 5. Cysteine-mediated induction of hepatic cysteine oxidase was partially inhibited by the simultaneous injection of cycloheximide, whereas hydrocortisone- and nicotinamide-mediated inductions were completely inhibited by cycloheximide.

Hypothalamic regulation of the daily rhythm in hepatic tyrosine transaminase activity.

THERE is a daily rhythm in the activity of tyrosine transaminase in rat liver1 which is characterized by a three-fold rise in enzyme activity from low daytime values to a peak several hours after dark. The oscillation persists in the absence of the pituitary or adrenal glands2–4 and during fasting5,6. Noradrenaline seems to play a role in the regulation of the enzyme and thereby contributes to the generation of the daily rhythm of activity7, but elevation of tissue noradrenaline in vivo suppresses the circadian enzyme rhythm at basal levels8. Noradrenaline inhibits tyrosine transaminase activity in vitro by competing with enzyme for binding with the pyridoxal-5′-phosphate co-factor7, and recent observations suggest that noradrenaline regulates tyrosine transaminase turnover in vivo by the same mechanism.

Cholinergic regulation of hepatic tyrosine transaminase activity.

1. The cholinergic agent carbachol (0.5 mg/kg) produces within 2 hr a two- to threefold increase in the activity of hepatic tyrosine transaminase in the adrenalectomized fasted rat.2. The carbachol-evoked rise in enzyme activity is prevented by pretreatment with atropine.3. Cycloheximide, an inhibitor of protein synthesis, prevents the carbachol-evoked rise of enzyme activity; actinomycin D, an inhibitor of RNA synthesis, partially reduces it.4. Atropine or unilateral (right or left) vagotomy suppresses the daily rhythm of tyrosine transaminase by attenuating the normal evening peak but not the normal lower daily levels of the enzyme.5. Electrical stimulation of the right vagus results in a significant elevation of tyrosine transaminase activity within 2 hr.6. The observations suggest that activity of vagal cholinergic nerves produces an RNA-dependent induction of hepatic tyrosine transaminase through a process requiring cholinergic-receptor stimulation. Intermittent activity of this vagal cholinergic system may contribute to the regulation of the daily rhythm in this enzyme.

Biphasic effect of norepinephrine in the regulation of hepatic tyrosine transaminase activity

Norepinephrine injection is associated with a biphasic response of heptatic tyrosine transaminase (tyrosine aminotransferase, l-tyrosine: 2-oxoglutarate aminotransferase EC 2.6.1.5) activity in the adrenalectomized and hypophysectomized rat. After an initial increase, enzyme activity falls below control levels. The increase in tyrosine transaminase activity is blocked by cycloheximide but not actinomycin D, ergotamine tartrate, or propranalol. Depression of tyrosine transaminase activity by norepinephrine is maximal at night when enzyme activity normally rises to peak levels, resulting in a suppression of the circadian enzyme rhythm. The decreased activity at night occurs without prior induction, indicating the independence of these two effects of norepinephrine. Evidence suggesting that norepinephrine depresses tyrosine transaminase activity by competing with apoenzyme for the pyridoxal-5′-phosphate cofactor is presented. These observations indicate that a regulator molecule may have multiple effects on an enzyme system varying not only with dosage but with time of administration.

Influence of feeding habits and adrenal cortex on diurnal rhythm of hepatic tyrosine transaminase activity.

Dietary intake and adrenal cortex effects on diurnal rhythm of hepatic tyrosine transaminase activity and adrenal corticosterone content in rats

The effects of some centrally acting drugs on the glucocorticold induction of hepatic tyrosine transaminase

The effects of some centrally acting drugs on hepatic tyrosine transaminase activity with and without cortisol in the adrenalectomized male and female rat have been determined. Tyrosine transaminase activity in the female adrenalectomized rat is higher than in the male and is less sensitive to drug augmentation of cortisol induction. Cortisol induction of tyrosine transaminase can be augmented by SKF 525-A 3 hours after cortisol injection. Induction of the enzyme by 16β-methylprednisone, oxylone, and fluocinolone acetonide can be augmented by SKF 525-A and by chlorpromazine.

Inhibition of Tyrosine Transaminase Activity by Norepinephrine

Abstract The neurotransmitter, norepinephrine, and structurally related primary catecholamines inhibited rat hepatic tyrosine transaminase activity (l-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) in vitro. The inhibition was competitive with pyridoxal 5'-phosphate cofactor and an apparent Ki of 4.0 x 10-6 m was determined. (The apparent Km was 6.6 x 10-7 m.) Those amines which were associated with enzyme inhibition formed spectrophotometrically demonstrable complexes with pyridoxal 5'-phosphate, and full enzyme inhibition was achieved by the preliminary incubation of norepinephrine and cofactor alone. The relevance of this mechanism of regulation was examined in vivo. Increasing doses of norepinephrine suppressed and ultimately abolished the pyridoxine-induced rise of tyrosine transaminase activity in the fasted, adrenalectomized rat.

Hepatic Tyrosine Transaminase Rhythm: Interaction of environmental lighting, food consumption and dietary protein content

Hepatic tyrosine transaminase activity was measured over a 24-hour period in animals maintained under three environmental situations: normal lighting (lights on from 9 AM to 9 PM) and ad libitum dietary protein; reversed lighting (lights on from 9 PM to 9 AM) and ad libitum dietary protein; and normal lighting and a nonprotein diet, with protein added at various times during the day. In each case, the increase in tyrosine transaminase activity was not observed until after the initial ingestion of protein. These results support the hypothesis that the daily rhythm in the activity of this enzyme in rat liver is generated by the cyclical ingestion of protein.

Endocrine influences on altered hepatic tyrosine transaminase activity during pneumococcal septicemia in the rat.

Protein metabolism during pneumococcal septicemia in the rat was studied in terms of a single protein, the hepatic enzyme tyrosine transaminase (TT). A large inoculum (107 organisms) was followed within 4 hr by elevation in TT activity, reaching a peak 8-fold over contz-ol 24–28 hr post infection. TT activity was greater after inoculation at 2200 than at 1000 hr. Higher fever and earlier bacteremia were observed following nocturnal inoculation. A small inoculum produced a rise in TT activity only after a delay of 24 hr. An increase in plasma corticosterone 2–4 hr before TT activity suggested a relationship between increased plasma steroid and enzyme activity, whether due to circadian periodicity in control rats or to infection. No TT response to infection occurred in adrenalectomized or hypophysectomized animals. Diminished TT response during infection in thyroidectomized animals and a failure of thyroxine to stimulate this enzyme suggested a secondary role of thyroxine in modulating adrenocortical steroi...

Suppression of the daily rhythm in tyrosine transaminase activity by acute elevation of norepinephrine.

THE enzyme tyrosine transaminase has a 24 h rhythm of activity in the rat liver which varies over a four-fold range each day1. This periodicity persists in the absence of pituitary or adrenal glands2–4, indicating that the driving oscillation of the rhythm does not reside in the pituitary-adrenal axis. Recent work in this laboratory5 has shown that depletion of tissue norepinephrine is associated with a three-fold increase in hepatic tyrosine transaminase activity in the fasted, adrenalectomized rat. This rise in enzyme activity was abolished by repletion of norepinephrine. These findings suggest that the neurohumour norepinephrine is involved in the generation of the daily rhythm in the activity of this enzyme. The results presented here show that a rise in tissue norepinephrine, either by inhibition of degradation or by increase in synthesis, is associated with a suppression of the diurnal rhythm of the rat hepatic enzyme.

Elevation and depression of hepatic tyrosine transaminase activity by depletion and repletion of norepinephrine.

Elevation and depression of hepatic tyrosine transaminase activity by depletion and repletion of norepinephrine.

Mechanism of the daily rhythm in hepatic tyrosine transaminase activity: role of dietary tryptophan.

Mechanism of the daily rhythm in hepatic tyrosine transaminase activity: role of dietary tryptophan.

Gluconeogenesis during hibernation and arousal from hibernation

1. 1. In the ground squirrel, Citellus tridecemlineatus, liver glycogen and blood glucose decreased during hibernation. Two hours after arousal, liver glycogen remained low but blood glucose was normal. 2. 2. When incubated at 6°C, kidney cortex slices from hibernating animals had a greater capacity for gluconeogenesis from α-ketoglutarate, l-glutamate, l-aspartate, glycerol, oxaloacetate, l-lactate and pyruvate than renal tissue from normothermic squirrels. At 40°C, glucose synthesis from l-aspartate, glycerol, l-lactate, oxaloacetate and pyruvate was significantly increased in renal tissue from hibernating and arousing animals. 3. 3. Hibernation and arousal were associated with significantly increased hepatic and renal lactic dehydrogenase and hepatic glutamic-oxaloacetic transaminase activities but glucose-6-phosphatase and fructose-1,6-diphosphatase activities remained unchanged. 4. 4. The role of gluconeogenesis during hibernation and arousal is discussed.

Interference of metyrapone with the actions of cortisol in Xenopus laevis Daudin and the laboratory rat

Injection of cortisol into X. laevis produced a decrease in body weight and increases in liver weight, hepatic glycogen content and transaminase activity. There was a large increase in the rate of excretion of urea while ammonia excretion was only slightly increased. In rats, cortisol injection was followed by decreased body and thymus weight and increases in liver weight, glycogen concentration and transaminase activity. In X. laevis, injection of metyrapone (SU4885) was followed by a slight decrease in body weight, a 50% decrease in the rate of urea excretion but no change in liver weight, glycogen concentration or transaminase activity or in the rate of excretion of ammonia. In the rat there was a slight decrease in thymus weight but no change in the other parameters of cortisol activity. Injection of metyrapone for several days followed by injection of metyrapone plus cortisol gave exactly the same results, in X. laevis, as injection of metyrapone alone. Following similar treatment in the rat, there was a slight decrease in body weight, no change in liver weight or glycogen concentration, a decrease in thymus weight and an increase in transaminase activity; in no case, however was the change as large as that which followed cortisol injection. It is concluded that metyrapone interferes in some way with the action of circulating cortisol as well as inhibiting its biosynthesis.

Effects of altered thyroid function in rats upon the formation and distribution of tyrosine.

The effects of altered thyroid status upon hepatic phenylalanine hydroxylase activity were studied in rats. After treatment with thyroxine, phenylalanine hydroxylase activity was unchanged; radiothyroidectomy produced a 27% decrease. These effects upon phenylalanine hydroxylase activity were minimal when compared to changes observed in hepatic tyrosine transaminase activity under similar conditions. Measui'ements of 14C-tyrosine disappearance from plasma demonstrated that treatment with thyroxine increased the fractional turnover rate of tyrosine. The “volume of distribution” of tyrosine in control rats was 1/3 greater than in thyroxine-treated rats. These studies suggest that the elevated concentration of tyrosine in plasma noted after administration of thyroxine is probably not derived from an enhanced conversion from phenylalanine, but more probably is related to the diminution in the “volume of distribution” of tyrosine, by mechanisms which have not been elucidated. The experiments provide further sup...

Effect of corticosteroids on tadpole hepatic transaminases

Activities of aspartate-α-ketoglutarate (E.C.2.6.1.1), alanine-α-ketoglutarate (E.C.2.6.1.2) and tyrosine-α-ketoglutarate (E.C.2.6.1.5) transaminases in the livers of tadpoles were determined and the effect of corticoids and tyrosine upon the hepatic activities of these three transaminase studied. In contrast to mammalian livers, neither hydrocortisone nor tyrosine caused an appreciable increase in hepatic transaminase activities in tadpoles. The hepatic transaminase activities were not affected by treatment of the tadpoles with Metopirone, an inhibitor which blocks the biosynthesis of corticoids in vivo.

Hepatic tyrosine transamina se activity and plasma tyrosine concentration in rats with altered thyroid function.

The activity of hepatic tyrosine- a-ketoglutarate transaminase, the first enzyme in the major degradative pathway of tyrosine metabolism, was measured in hyperthyroid, athyrotic and euthyroid male rats. Treatment of 15 rats with L-thyroxine for 4–6 weeks increased enzyme activity from 89.7 Mmoles p-hydroxyphenylpyruvic acid formed/g dry wt/hr to 126, whereas radiothyroidectomy of 12 rats decreased enzyme activity to 44 μmoles. Tyrosine transaminase activity of the athyrotic rats was not changed by adrenalectomy. To test the specificity of the changes in tyrosine transaminase activity, a related enzyme, phenylalanine-pyruvate transaminase, was simultaneously assayed and was found to be unaltered by any changes in thyroid function. Plasma tyrosine concentration increased from 14.1 μg/ml to 17.1 in rats chronically treated with thyroxine and decreased to 11.5 μg/ml after radiothyroidectomy. L-Thyroxine treatment for only 1–3 days increased plasma tyrosine levels, but hepatic tyrosine transaminase activity was unchanged. Since chronic thyroxine treatment resulted in higher levels of plasma tyrosine, as well as in a simultaneous increase in hepatic tyrosine transaminase activity, it is suggested that separate mechanisms may control the activity of the liver enzyme and the level of tyrosine in the plasma.

Inhibition of hepatic alanine transaminase activity in response to treatment with 11-deoxycorticosterone.

SummaryDaily administration of DOC for short periods resulted in a 60 to 70% depression in liver alanine transaminase activity. Adrenalectomy also caused a decrease in activity of alanine transaminase, but no further reduction in the level of this enzyme was observed upon treatment with DOC. Treatment with ACTH resulted in an increase in alanine transaminase activity in hypophysectomized rats, but not in adrenalectomized animals. Administration of DOC to hypophysectomized rats failed to lower alanine transaminase, nor did it alter the response of this enzyme to treatment with ACTH. The inhibitory effect of DOC on alanine transaminase activity appears to be due to suppression of ACTH release by the pituitary.