Development of gluconeogenesis in neonatal rat liver. Effect of premature delivery

1. An assay method for the determination of phosphopyruvate carboxylase activity is described in which improved sensitivity is obtained by separation of the enzyme from interfering pyruvate kinase by zone sedimentation. 2. The molecular weight of rat liver phosphopyruvate carboxylase determined by zone sedimentation is about 68000. 3. Premature delivery of rat foetuses by uterine section results in the rapid appearance of phosphopyruvate carboxylase, but hexose diphosphatase and pyruvate carboxylase, already present in the foetal rat liver, are not significantly affected, and glucose 6-phosphatase activity is only slightly affected. 4. The rate of incorporation of [¹⁴C]pyruvate into glucose by liver slices is also greatly increased by premature delivery and there is a highly significant linear correlation between this process and the phosphopyruvate carboxylase activity.     

Changes in activity of some enzymes involved in glucose utilization and formation in developing rat liver

1. The activities of some enzymes involved in both the utilization of glucose (pyruvate kinase, ATP citrate lyase, NADP-specific malate dehydrogenase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-specific isocitrate dehydrogenase, all present in the supernatant fraction of liver homogenates) and the formation of glucose by gluconeogenesis (glucose 6-phosphatase in the whole homogenate and fructose 1,6-diphosphatase, phosphopyruvate carboxylase, NAD-specific malate dehydrogenase and fumarase in the supernatant fraction) have been determined in rat liver around birth and in the postnatal period until the end of weaning. 2. The activities of those enzymes involved in the conversion of glucose into lipid are low during the neonatal period and increase with weaning. NADP-specific malate dehydrogenase first appears and develops at the beginning of the weaning period. 3. The marked increase in cytoplasmic phosphopyruvate carboxylase activity at birth is probably the major factor initiating gluconeogenesis at that time. 4. The results are discussed against the known changes in dietary supplies and the known metabolic patterns during the period of development.     

A comparison of the properties of fructose 1,6-diphosphatase, and the activities of other key enzymes of carbohydrate metabolism, in the livers of embryonic and adult rat, sheep and domestic fowl

1. The activities of some key enzymes of glycolysis and gluconeogenesis were measured in embryonic chick, sheep and rat livers. 2. In chicken the activities of hexokinase, phosphofructokinase and pyruvate kinase are low, but those of glucose 6-phosphatase and fructose diphosphatase are very high; the converse situation exists in the rat (Burch et al. 1963), but in sheep the activities of both phosphofructokinase and fructose diphosphatase are high, and the activities of hexokinase and glucose 6-phosphatase are low. These findings are discussed in relation to carbohydrate metabolism in these embryonic livers. 3. The regulatory properties of fructose diphosphatase from the embryonic livers of these three species were compared with the properties of the enzymes from adult animals. The inhibitions by AMP and fructose diphosphate and the effects of Mg(2+) and pH on the activities of adult and foetal fructose diphosphatase are almost identical. 4. It is concluded that regulatory properties are characteristic of fructose diphosphatase from embryonic and adult tissue, and the importance of this in relation to enzyme development is discussed.     

Carbohydrate metabolism in liver from foetal and neonatal sheep

1. During development of the sheep, the activities of UDP-glucose–α-glucan glucosyltransferase and UDP-glucose pyrophosphorylase and the glycogen content are highest in the liver of lambs 2 weeks old and considerably lower in liver from adult sheep. 2. The activity of hexokinase and the rate of incorporation of [¹⁴C]-glucose into glycogen are much lower in liver from postnatal sheep than in rat liver. 3. The activities of hexose diphosphatase and glucose 6-phosphatase and the rates of incorporation of [¹⁴C]pyruvate and [¹⁴C]propionate into glycogen increase from low levels in the liver of foetal sheep to maxima a few weeks after birth. The activities in the liver of adult sheep are slightly lower. 4. The incorporation rate of [¹⁴C]pyruvate into glucose has been measured in liver slices from rats, sheep and chick embryos at several ages of these animals. This pathway is active in liver from foetal sheep, embryonic chicks and postnatal rats or sheep, but is absent from the liver from foetal rats. 5. Fructose metabolism, as measured by the rates of incorporation of [¹⁴C]fructose into glycogen and glucose in liver slices and by assays of liver ketohexokinase, is barely detectable in the liver of foetal sheep and appears soon after birth. 6. During development of the sheep, the incorporation rate of [¹⁴C]galactose into glycogen in liver slices is highest in foetal sheep and decreases with increasing age of the animal. 7. These findings are discussed with reference to the changing pattern of carbohydrate metabolism during neonatal development of liver in the sheep.     

Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver

1. Phosphopyruvate carboxylase activity rapidly appears in the liver of prematurely delivered rats and development of activity is prevented by injection of actinomycin D just before delivery. 2. The activity is considerably decreased by puromycin and amino acid analogues and thus appears to be due to enzyme synthesis. 3. Newborn or premature animals show a transient intense phase of hypoglycaemia after delivery. 4. When the hypoglycaemic phase is prevented by glucose injection little phosphopyruvate carboxylase activity appears in the liver, but galactose, mannose and fructose, which have no effect on the blood glucose concentration, also repress enzyme development. 5. Lactate, pyruvate and glycerol injections repress the premature development of phosphopyruvate carboxylase. 6. Injections of glucagon, adrenalin and noradrenalin into the rat foetus in utero result in development of phosphopyruvate carboxylase activity. 7. These findings are discussed in relation to the mechanism of initiation of enzyme synthesis in neonatal rat liver.     

Gluconeogenesis in developing rat kidney cortex

1. Gluconeogenesis in developing rat kidney cortex was studied by assaying the activities of two enzymes, glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, and by measuring glucose formation in tissue slices. 2. Glucose 6-phosphatase and phosphoenolpyruvate carboxykinase are present in late foetal (21-22-day-old) tissue and increase rapidly postnatally. Maximum activity of phosphoenolpyruvate carboxykinase occurs at 7 days of age, followed by a decline to the adult level. Glucose 6-phosphatase activity rises during the first 2 postnatal weeks and then declines. 3. Late foetuses synthesize glucose from both pyruvate and l-glutamate. The rate increases during the first 2 weeks to above adult levels. Synthesis is always higher from pyruvate than from glutamate. 4. The effect of 24hr. starvation was studied in perinatal animals. The results indicate that the ability to increase the rate of glucose synthesis as a result of starvation is not present at birth, but develops some time after the second postnatal day.     

The appearance of gluconeogenesis at birth in sheep. Activation of the pathway associated with blood oxygenation.

1. Measurements of pyruvate carboxylase, mitochondrial phosphoenolpyruvate carboxykinase (GTP), hexose bisphosphatase and glucose 6-phosphatase in developing sheep liver showed substantial activities of all enzymes in the foetus, especially towards the end of gestation. Cytosol phosphoenolpyruvate carboxykinase (GTP) in livers of mid-term foetuses was only 10% of the activity at birth. 2. All enzymes except pyruvate carboxylase showed 1.5-2-fold increases after birth. 3. Gluconeogenesis form [14C]actate could not be detected in chronically cannulated sheep foetuses at any developmental stage and was not initiated by the infusion of adrenaline or glucagon. 4. An active pathway of gluconeogenesis was evident in vivo within 2 min after natural birth or within 4 min after Caesarian delivery of term lambs, and was delayed in prematurely delivered lambs until breathing was established and the blood fully oxygenated. 5. It is proposed that oxygen availability initiates gluconeogenesis in the newborn lamb.     

Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver

1. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase were measured in foetal, newborn and adult rat liver extracts by a radiochemical assay involving the fixation of [¹⁴C]bicarbonate. 2. Pyruvate-carboxylase activity in both foetal and adult liver occurs mainly in mitochondrial and nuclear fractions, with about 10% of the activity in the cytoplasm. 3. Similar studies of the intracellular distribution of phosphoenolpyruvate carboxykinase show that more than 90% of the activity is in the cytoplasm. However, in the 17-day foetal liver about 90% of the activity is in mitochondria and nuclei. 4. Pyruvate-carboxylase activity in both particulate and soluble fractions is very low in the 17-day foetal liver and increases to near adult levels before birth. 5. Phosphoenolpyruvate-carboxykinase activity in the soluble cell fraction increases 25-fold in the first 2 days after birth. This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. 6. Kinetic and other studies on the properties of phosphoenolpyruvate carboxykinase have shown no differences between the soluble and mitochondrial enzymes. 7. It is suggested that the appearance of the soluble phosphoenolpyruvate carboxykinase at birth initiates the rapid increase in overall gluconeogenesis at this stage.     

The activities of fructose 1,6-diphosphatase, phosphofructokinase and phosphoenolpyruvate carboxykinase in white muscle and red muscle

1. The activities of fructose 1,6-diphosphatase were measured in extracts of muscles of various physiological function, and compared with the activities of other enzymes including phosphofructokinase, phosphoenolpyruvate carboxykinase and the lactate-dehydrogenase isoenzymes. 2. The activity of phosphofructokinase greatly exceeded that of fructose diphosphatase in all muscles tested, and it is concluded that fructose diphosphatase could not play any significant role in the regulation of fructose 6-phosphate phosphorylation in muscle. 3. Fructose-diphosphatase activity was highest in white muscle and low in red muscle. No activity was detected in heart or a deep-red skeletal muscle, rabbit semitendinosus. 4. The lactate-dehydrogenase isoenzyme ratio (activities at high and low substrate concentration) was measured in various muscles because a low ratio is characteristic of muscles that are more dependent on glycolysis for their energy production. As the ratio decreased the activity of fructose diphosphatase increased, which suggests that highest fructose-diphosphatase activity is found in muscles that depend most on glycolysis. 5. There was a good correlation between the activities of fructose diphosphatase and phosphoenolpyruvate carboxykinase in white muscle, where the activities of these enzymes were similar to those of liver and kidney cortex. However, the activities of pyruvate carboxylase and glucose 6-phosphatase were very low in white muscle, thereby excluding the possibility of gluconeogenesis from pyruvate and lactate. 6. It is suggested that the presence of fructose diphosphatase and phosphoenolpyruvate carboxykinase in white muscle may be related to operation of the alpha-glycerophosphate-dihydroxyacetone phosphate and malate-oxaloacetate cycles in this tissue.     

The effects of pregnancy and lactation on the activities in rat liver of some enzymes associated with glucose metabolism.

1. The ratio of the combined activities of hexokinase (EC 2.7.1.1) and glucokinase (EC 2.7.1.2) to the activity of glucose-6-phosphatase (EC 3.1.3.9) changed in favour of the glycolytic enzymes during pregnancy and at peak lactation. 2. There were no important changes in the ratio of the activity of phosphofructokinase (EC 2.7.1.11) to that of fructose diphosphatase (EC 3.1.3.11). 3. The ratio of the activity of pyruvate kinase (EC 2.7.1.40) to the combined activities of phosphoenolpyruvate carboxylase (EE 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1) changed in favour of the glycolytic enzyme during pregnancy and at peak lactation, but changed in favour of the gluconeogenic enzymes immediately after parturition. 4. These changes are considered in relation to the changes in food intake and hormonal status that occur during pregnancy and lactation.     

Changes in the properties of fetal rat liver during organ culture

Summary Explants of fetal rat liver maintained in organ culture lost about 40% of their mass in 42 hr of incubation as a result of decrease in blood cells and hepatocytes. Proteins from the cytosol and particulate elements of the tissue were found in the culture medium. About 60% of this protein was degraded to peptides during culture. The transfer of malate and lactate dehydrogenases from tissue to medium paralleled that of proteins. Glutamate dehydrogenase was lost from the mitochondria and in part leaked through the cell membrane into the medium. Net loss of activity of the three enzymes occurred, probably as a consequence of proteolytic degradation. Of 12 enzymes in liver tissue, the specific activities of eight—soluble malate dehydrogenase, glutamate dehydrogenase, succinate dehydrogenase, phosphopyruvate carboxylase, hexosediphosphatase, glucose-6-phosphatase, tyrosine, aminotransferase, and alanine aminotransferase—were unchanged or increased. Glycogen synthetase, aspartate aminotransferase, pyruvate kinase, and lactate dehydrogenase decreased. Although changes in membrane permeability may have had some influence on the results reported, the predominant effect was due to loss of protein from tissue as a result of discharge of total contents of some of the cells into the medium. The residual explanted tissue retained its structural integrity. It is concluded that fetal rat liver in organ culture provides a suitable model system for controlled studies with this organ in vitro. This investigation was supported by grants from the National Institute of Child Health and Human Development (RO 1 HD09715), National Cancer Institute (CA 14194), and United States Public Health Service General Research Support Grant RR 5589.     

Location of three key enzymes of gluconeogenesis in baker's yeast

The subcellular location of hexose diphosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in baker's yeast (Saccharomyces cerevisiae) was investigated by density gradient centrifugation of spheroplast lysates obtained by osmotic shock treatment of spheroplasts and centrifugation for 10000 g x min. On the evidence obtained from zonal separations these three enzymes of gluconeogenesis are most probably located in the soluble cytosol.List of Abbreviations HDPase Hexose diphosphatase - PEPCK Phosphoenolpyruvate carboxykinase - PC Pyruvate carboxylase     

Factors influencing the development of urea-synthesizing enzymes in rat liver

1. The activities of enzymes of the urea cycle, carbamoyl phosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinase (the last two comprising the arginine synthetase system) and arginase, were measured in the liver during development of the rat. All five enzymes exhibited relatively low activities in foetal liver and a rapid postnatal increase was found. The rate-limiting enzyme of urea synthesis in the rat, the condensing enzyme of the arginine synthetase system, showed the lowest activity at birth and the most rapid postnatal increase, a fivefold increase within 24hr. after birth. A second increase of activity was noted after the tenth day. These results suggest that the postnatal increase of arginine synthetase activity initiates the ability for urea synthesis in the rat. 2. Some factors influencing the development of the rate-limiting arginine synthetase system were studied in more detail. (a) Intraperitoneal administration of puromycin inhibited the postnatal increaseof the enzyme activity. (b) Starvation of newborn animals for 24hr. after birth had no effect on the postnatal development of the enzyme. (c) Bilateral adrenalectomy at birth caused a marked diminution in the postnatal increase of the enzyme activity and injections of triamcinolone were effective in preventing the effect of adrenalectomy. (d) Administration of triamcinolone alone had a marked stimulatory effect on the postnatal development of this enzyme. (e) Premature and postmature birth had virtually no effect on the developmental pattern of the arginine synthetase activity, suggesting that the increase of this enzyme activity after birth is not initiated by the birth process.     

Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate

1. Measurements were made of the activities of the four key enzymes involved in gluconeogenesis, pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxylase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), of serine dehydratase (EC 4.2.1.13) and of the four enzymes unique to glycolysis, glucokinase (EC 2.7.1.2), hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40), in livers from starved rats perfused with glucose, fructose or lactate. Changes in perfusate concentrations of glucose, fructose, lactate, pyruvate, urea and amino acid were monitored for each perfusion. 2. Addition of 15mm-glucose at the start of perfusion decreased the activity of pyruvate carboxylase. Constant infusion of glucose to maintain the concentration also decreased the activities of phosphoenolpyruvate carboxylase, fructose 1,6-diphosphatase and serine dehydratase. Addition of 2.2mm-glucose initially to give a perfusate sugar concentration similar to the blood sugar concentration of starved animals had no effect on the activities of the enzymes compared with zero-time controls. 3. Addition of 15mm-fructose initially decreased glucokinase activity. Constant infusion of fructose decreased activities of glucokinase, phosphofructokinase, pyruvate carboxylase, phosphoenolpyruvate carboxylase, glucose 6-phosphatase and serine dehydratase. 4. Addition of 7mm-lactate initially elevated the activity of pyruvate carboxylase, as also did constant infusion; maintenance of a perfusate lactate concentration of 18mm induced both pyruvate carboxylase and phosphoenolpyruvate carboxylase activities. 5. Addition of cycloheximide had no effect on the activities of the enzymes after 4h of perfusion at either low or high concentrations of glucose or at high lactate concentration. Cycloheximide also prevented the loss or induction of pyruvate carboxylase and phosphoenolpyruvate carboxylase activities with high substrate concentrations. 6. Significant amounts of glycogen were deposited in all perfusions, except for those containing cycloheximide at the lowest glucose concentration. Lipid was found to increase only in the experiments with high fructose concentrations. 7. Perfusion with either fructose or glucose decreased the rates of ureogenesis; addition of cycloheximide increased urea efflux from the liver.     

A comparison of the effects of diabetes induced with either alloxan or streptozotocin and of starvation on the activities in rat liver of the key enzymes of gluconeogenesis

1. Measurements of the activities in rat liver of the four key enzymes involved in gluconeogenesis, i.e. pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxykinase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), have been carried out, all four enzymes being measured in the same liver sample. Changes in activities resulting from starvation and diabetes have been studied. Changes in concentration (activity/unit wet weight of tissue) were compared with changes in the hepatic cellular content (activity/unit of DNA). 2. Each enzyme was found to increase in concentration during starvation for up to 3 days, but only glucose 6-phosphatase and phosphoenolpyruvate carboxykinase showed a significant rise in content. Fructose 1,6-diphosphatase appeared to decrease in content somewhat during the early stages of starvation. 3. There was a marked increase in the concentration of all four enzymes in non-starved rats made diabetic with alloxan or streptozotocin, for the most part similar responses being found for the two diabetogenic agents. On starvation, however, the enzyme contents in the diabetic animals tended to fall, often with streptozotocin-treated animals to values no greater than for the normal overnight-starved rat. Deprivation of food during the period after induction of diabetes with streptozotocin lessened the rise in enzyme activity. 4. The results are compared with other published values and factors such as substrate and activator concentrations likely to influence activity in vivo are considered. 5. Lack of correlation of change in fructose 1,6-diphosphatase with the other enzymes questions whether it should be included in any postulation of control of gluconeogenic enzymes by a single gene unit.     

Fructose 1,6-diphosphatase in striated muscle

1. The occurrence of fructose diphosphatase in muscle tissue was investigated with reference to the question whether lactate can be converted into glycogen in muscle, as postulated by Meyerhof (1930), fructose diphosphatase being one of the enzymes required for this conversion. 2. Fructose diphosphatase was found in skeletal muscle of man, dog, cat, rat, mouse, rabbit, guinea pig, cattle, sheep, pigeon, fowl and frog. Under the test conditions between 5 and 60 μmoles of substrate were split/g. fresh wt./hr. at 22°. 3. Like liver fructose diphosphatase, the muscle enzyme is inhibited by substrate concentrations above 0·1 mm, by AMP and by trace quantities of Zn²⁺, Fe²⁺ and Fe³⁺; it is `activated' by EDTA. Inhibitions by the above agents may account for the failure of previous authors to detect the enzyme. 4. Heart muscle of several vertebrate species and the smooth muscle of pigeon and fowl gizzard had no measurable activity. 5. The presence of fructose diphosphatase and the virtual absence of the enzyme systems converting pyruvate into phosphopyruvate means that lactate and pyruvate cannot be converted into glycogen in muscle, whereas the phosphorylated C₃ compounds can. The reconversion into carbohydrate of lactate (which readily diffuses out of muscle) occurs in liver and kidney only. The reconversion of phosphorylated C₃ intermediates (which cannot diffuse out of the tissue) can occur only within the muscle. 6. α-Glycerophosphate is probably the main intermediate requiring conversion into glycogen. The possible role of α-glycerophosphate formation in vertebrate muscle, already well established in insect muscle, is discussed.     

Metabolic control of hepatic gluconeogenesis during exercise.

Prolonged exercise increased the concentrations of the hexose phosphates and phosphoenolpyruvate and depressed those of fructose 1,6-bisphosphate, triose phosphates and pyruvate in the liver of the rat. Since exercise increases gluconeogenic flux, these changes in metabolite concentrations suggest that metabolic control is exerted, at least, at the fructose 6-phosphate/fructose 1,6-bisphosphate and phosphoenolpyruvate/pyruvate substrate cycles. Exercise increased the maximal activities of glucose 6-phosphatase, fructose 1,6-bisphosphatase, pyruvate kinase and pyruvate carboxylase in the liver, but there were no changes in those of glucokinase, 6-phosphofructokinase and phosphoenolpyruvate carboxykinase. Exercise changed the concentrations of several allosteric effectors of the glycolytic or gluconeogenic enzymes in liver; the concentrations of acetyl-CoA, ADP and AMP were increased, whereas those of ATP, fructose 1,6-bisphosphate and fructose 2,6-bisphosphate were decreased. The effect of exercise on the phosphorylation-dephosphorylation state of pyruvate kinase was investigated by measuring the activities under conditions of saturating and subsaturating concentrations of substrate. The submaximal activity of pyruvate kinase (0.5 mM-phosphoenolpyruvate), expressed as percentage of Vmax., decreased in the exercised animals to less than half that found in the controls. These changes suggest that hepatic pyruvate kinase is less active during exercise, possibly owing to phosphorylation of the enzyme, and this may play a role in increasing the rate of gluconeogenesis.     

Biochemical aspects of bovine ketosis

1. The concentrations of acetoacetate, β-hydroxybutyrate and metabolites related to gluconeogenesis were determined in biopsy samples of the livers of ketotic, normal lactating and normal non-lactating cows. Key enzymes of gluconeogenesis in the liver were also assayed. 2. Significant decreases were found in the ketotic liver in the concentrations of glucogenic amino acids (glutamate, glutamine, alanine) and of glucogenic oxo acids (α-oxoglutarate, pyruvate, oxaloacetate). 3. The β-hydroxybutyrate/acetoacetate concentration ratios were generally much higher than in rat liver. 4. The concentration of total fat was sevenfold higher in the ketotic liver, and that of glucose plus glycogen fourfold lower than in normal liver. 5. The blood of ketotic cows showed a marked rise in the concentration of free fatty acids. 6. The activities of pyruvate carboxylase, propionyl-CoA carboxylase, phosphopyruvate carboxylase and fructose 1,6-diphosphatase showed no clear-cut differences between normal and ketotic animals. 7. Glucose injection promptly relieved the ketotic condition with respect to both the clinical and biochemical signs. The fall in the concentrations of the ketone bodies in the blood was preceded by a fall in the concentrations of free fatty acids and glycerol. 8. The findings are taken to be consistent with the concept that an increased rate of gluconeogenesis, causing a decrease in the concentration of oxaloacetate, is a major causal factor in ketogenesis.     

Phosphatase activities in rat liver before and after birth

Synopsis Several phosphatase enzymes have been studied biochemically and cytochemically to ascertain whether there are ontogenic changes in level or location. Nucleoside monophosphatase (5-nucleotidase) and lysosomal acid phosphatase are low in foetal liver and, unlike glucose-6-phosphatase, are still quite low in neonatal liver. Bile canaliculi show strong staining for 5-nucleotidase in adult liver but not in foetal or neonatal liver. Nucleoside diand triphosphatase activities in foetal liver are already near half the adult level. The diphosphatase that is active towards UDP shows the same cytochemical locations in neonatal liver as in adult liver. Triphosphatase activity in foetal and neonatal liver is located largely in star-like cells, rather than in the bile canaliculi of parenchymal cells. Biochemical comparison of foetal, neonatal and adult liver has shown that inorganic pyrophosphatase (assayed without Mg²⁺) parallels glucose-6-phosphatase, but acid ribonuclease does not parallel acid phosphatase. In albino rats injected with thyroxine, glucose-6-phosphatase has shown a more marked increase in foetal liver than in adult liver, although the uptake of thyroxine seemed to be less. In hooded rats, foetal liver showed a negligible uptake of thyroxine and no rise in glucose-6-phosphatase.A. A. El-Aaser is on leave from the Faculty of Medicine, University of Cairo.     

The interaction of catecholamines and adrenal corticosteroids in the induction of phosphopyruvate carboxylase in rat liver and adipose tissue

Catecholamines induced an increase in the activity of rat adipose tissue and liver phosphopyruvate carboxylases that was maintained for 48h. The response of adipose tissue phosphopyruvate carboxylase was blocked by actinomycin D, corticosteroids and propranolol, whereas corticosteroids and propranolol did not affect the liver enzyme. Cortisol phosphate, like actinomycin D, interfered only with the initiation of the increase in enzyme activity caused by noradrenaline, but not with the process of enzyme accumulation. In contrast, cycloheximide was effective in blocking enzyme induction throughout the course of the catecholamine effect. Adrenocorticotrophic hormone caused a short-term induction of adipose tissue phosphopyruvate carboxylase, which could be blocked by propranolol. Hepatic phosphopyruvate carboxylase, but not the adipose tissue enzyme, was induced by dibutyryladenosine 3':5'-cyclic monophosphate and by glucagon. Both nicotinic acid and nicotinamide decreased the normal induction of adipose tissue phosphopyruvate carboxylase caused by starvation, but only nicotinamide increased the activity of the liver enzyme.