Time-dependent variations in amino acid metabolism: mechanism of the tyrosine transaminase rhythm in rat liver

doi:10.1016/0065-2571(69)90010-7

Advances in Enzyme Regulation

Volume 7, 1969, Pages 57-67

https://doi.org/10.1016/0065-2571(69)90010-7 Get rights and content

Abstract

Daily rhythms in tissue enzyme activity might result from oscillating signals originating (a) within the cells that contain the enzyme; (b) endogenously but elsewhere in the body (e.g., in the brain); or (c) exogenously, as a direct result of environmental cycles. The activity of tyrosine transaminase in the rat liver shows marked time-dependent variations that appear to be generated by the interaction of an endogenous factor (the tendency of the animal to eat cyclically) and an exogenous factor (the presence of protein in the diet). Late in the daylight period, the animal begins to increase its rate of food consumption; as a result, the liver is perfused cyclically with relatively large amounts of tryptophan and other amino acids via the portal circulation. These amino acids act as a signal which instructs the hepatic cells to increase the activity of the transaminase.

The concentrations of tyrosine and other amino acids in human plasma also show regular diurnal fluctuations. These rhythms appear to be generated by other mechanisms in addition to the enzyme rhythms inasmuch as they involve all the amino acids and persist in subjects fed only minimal amounts of protein.

A recognition of the fact that “normal” levels of enzyme activity may vary markedly as a function of time of day is essential to the interpretation of the effects of experimental manipulations on enzyme activity.

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Cited by (10)

Morphine inhibition of the insulin-inducible form of hepatic tyrosine aminotransferase
1984, Biochemical Pharmacology
Morphine treatment in normal intact rats caused a dose-dependent increase in hepatic tyrosine aminotransferase (TAT) activity, as demonstrable up to 2 hr of exposure to the opioid alkaloid. However, such increase in TAT activity was invariably preceded by a prior decline in the enzyme level, as observed after 15 min of morphine treatment. Such an initial decline in activity was not demonstrable in diabetic animals. Further studies indicate that morphine inhibited the insulin-induced increase in TAT activity, a phenomenon which could be reversed by the opioid antagonist naloxone. The results suggest an opioid control mechanism in the regulation of the insulin-inducible form of TAT and indicate the possibilities of a trophic role of endogenous opiates in gluconeogenesis.
Liver tyrosine-alpha-ketoglutarate transaminase as a quantitative test of the phlogistic potency of agents topically applied
1976, Pharmacological Research Communications
The liver tyrosine-alpha-keto-glutarate transaminase (TKT) increase, provoked in rats by topical application on the conjunctiva of various phlogistic agents such as croton oil, mustard oil, formaldehyde and veratrine sulphate, is shown to be available as test for a quantitative evaluation of the so elicited inflammation.
In fact, the TKT increase (measured at the 150th min after the application) is linearly related to the log of increasing concentration of the tested drugs and the parallelism of the calculated regression lines enables to calculate the potency of various agents with reference to croton oil, the comparison of the test with the adrenal ascorbic acid (AAA) depletion test, simultaneously evaluated, shows a substantial agreement of the values of the potencies and their precision.
On the basis of the well-known relationship between glucocorticoid secretion and AAA depletion and TKT increase, the hypothesis that any phlogistic drug stimulates the hypothalamus pituitary-adrenal axis isconfirmed.
[41] Biological Rhythmicity Influencing Hormonally Inducible Events
1975, Methods in Enzymology
The necessity for controlling the time factor in studies of enzyme regulation derives from an increasing number of investigations reporting significant circadian changes in the activity of several hepatic enzymes that metabolize amino acids. If the product of a specifically directed protein synthesis demonstrates cyclic behavior, it follows that the biochemical steps that precede that enzyme activity (enzyme synthesis and synthesis of specific RNA species) could also be expected to exhibit endogenous rhythmicity. Circadian rhythms have been noted for DNA synthesis, RNA synthesis, mitotic index, and alterations in the nature of endoplasmic reticulum, as well as for a number of liver enzymes and secretory products of endocrine glands. In seeking to investigate cause and effect relationships, it would seem necessary to delineate whether reported changes were vicarious or programmatically directed. In the latter case, a particular study could be designed to maximize the results and avoid confusion between coincidence and correlation. The internal variations in cellular activity that have been cited are biological processes prone to synchronization and direction by external correlates. The integration of these signals is manifest in the operation of biological clocks that set the phasing and rhythm of cellular and holobiological events.
Diurnal rhythmicity of mammalian DNA-dependent RNA polymerase activities I and II: Dependence on food intake
1973, Biochemical and Biophysical Research Communications
Diurnal variations of DNA-dependent RNA polymerase activities I and II have been found in rats maintained under controlled feeding schedules. RNA polymerase I has two peaks of activity in a 24-hours cycle: one 6 hours after the onset of dark period and a second one in the middle of the light period. Polymerase II shows only one peak coinciding with the first one of polymerase I. These diurnal fluctuations are not present in the liver of rats denied food on the day of the experiment. Both polymerases do not exibit different optima for divalent metal ions and ionic strength in the different feeding conditions studied.
Biochemical studies on cells isolated from adult rat liver
1970, Experimental Cell Research
The conditions influencing the isolation of biochemically intact hepatocytes from adult rat liver by means of a modified Potter-Elvehjem homogenizer have been examined. Perfusion of the liver with a minimal volume (25–30 ml) of Ca²⁺-free Locke solution (containing 0.027 M citrate) pH 7.4 at 37 °C gave the highest cell yield (62.0 ± 7.0 × 10⁶ cells/g wet wt of liver) on subsequent dispersion in 0.25 M sucrose pH 7.4. The temperature of dispersion was not critical.
Hepatocytes obtained under optimal conditions had a linear or near-linear oxygen consumption over 50–60 min in all media tested including balanced saline solutions, and a mean QO₂ value of 6.5 ± 1.0 in 0.02 M Tris = HCl-0.1 M sucrose, which was the most suitable incubation medium for respiration studies. Washing the cells decreased their respiratory capacity only slightly. The cells retained 27% lactate dehydrogenase and 19% tyrosine-α-ketoglutarate transaminase after dispersion.
Several high-viscosity protective agents, such as polyvinyl alcohol, were added to the dispersion medium; although it was possible to decrease enzyme leakage from the cells, the respiration pattern of the hepatocytes was altered. Respiration was linear for only a short period of time (10–20 min) or the oxygen uptake was greatly reduced by washing the cells.
Hepatocytes obtained by dispersion of the liver with tetraphenylboron had a low enzyme retention and almost negligible oxygen consumption.
The importance of using more than one parameter to assess the biochemical integrity of isolated cells is emphasized.
The results are in accord with the view that enzyme leakage from dispersed liver cells is not energy dependent but due to a change in cell permeability; the increased permeability may be consequent to disorganization of the liver and is not rapidly reversible.
Regulation of Hepatic 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase
2006, Advances in Enzymology and Related Areas of Molecular Biology

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^☆: These studies were supported in part by grants from the National Institutes of Health (AM-11237 and AM-11709) and the National Aeronautics and Space Administration (NGR-22-009-272)

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Advances in Enzyme Regulation

Abstract

References (22)

Control of hydroxyindole-O-methyl transferase activity in the rat pineal gland by environmental lighting

J. Biol. Chem.

Circadian rhythm in hepatic drug metabolizing activity in the rat

Life Sci.

Comparison of the effect of amino acid supply on hepatic polysome profiles in vivo and in vitro

Biochim. Biophys. Acta

Effect of dietary tryptophan on hepatic polyribosomes and protein synthesis in fasted mice

J. Biol. Chem.

Ambiguities in the use of the term circadian

Science

Circadian rhythms and the circadian organization of living systems

Physiologic 24-hour periodicity in human beings and mice, the lighting regimen and daily routine

Daily rhythmic changes in tyrosine transaminase activity of the rat liver

Circadian rhythms of liver enzymes and their relationship to enzyme induction

Science

Hormonal factors altering rhythmicity of tyrosine-alpha-ketoglutarate transaminase in rat liver

Endocrinology

Specificity of the adaptive response of tyrosine-α-ketoglutarate transaminase in the rat

J. Biol. Chem.

Cited by (10)

Morphine inhibition of the insulin-inducible form of hepatic tyrosine aminotransferase

Liver tyrosine-alpha-ketoglutarate transaminase as a quantitative test of the phlogistic potency of agents topically applied

[41] Biological Rhythmicity Influencing Hormonally Inducible Events

Diurnal rhythmicity of mammalian DNA-dependent RNA polymerase activities I and II: Dependence on food intake

Biochemical studies on cells isolated from adult rat liver

Regulation of Hepatic 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase

Session III Regulation and cyclic changes in enzyme activities Session Chairman: V. R. PotterTime-dependent variations in amino acid metabolism: mechanism of the tyrosine transaminase rhythm in rat liver☆

Abstract

J. Biol. Chem.

Life Sci.

Biochim. Biophys. Acta

J. Biol. Chem.

Ambiguities in the use of the term circadian

Science

Circadian rhythms and the circadian organization of living systems

Physiologic 24-hour periodicity in human beings and mice, the lighting regimen and daily routine

Daily rhythmic changes in tyrosine transaminase activity of the rat liver

Circadian rhythms of liver enzymes and their relationship to enzyme induction

Science

Hormonal factors altering rhythmicity of tyrosine-alpha-ketoglutarate transaminase in rat liver

Endocrinology

Specificity of the adaptive response of tyrosine-α-ketoglutarate transaminase in the rat

J. Biol. Chem.

Session III Regulation and cyclic changes in enzyme activities Session Chairman: V. R. Potter
Time-dependent variations in amino acid metabolism: mechanism of the tyrosine transaminase rhythm in rat liver☆