Hepatic Glucose 6-phosphate Research Articles

Investigation of hepatic ATP and glucose 6-phosphate as indices of hypoglycin toxicity

The levels of ATP and of glucose 6-phosphate in livers of rats treated with hypoglycin (α- l-amino-β-methylenecyclopropanepropionic acid) have been investigated. This toxic amino acid found in fruits of the ackee plant ( Blighia sapida, König) is a hypoglycaemic agent. It was found that the hepatic pool of glucose 6-phosphate was markedly reduced by the treatment. This provided confirmatory evidence of depressed gluconeogenesis which contributes to the hypoglycaemia. Effects on levels of hepatic ATP were minimal and hence did not account for the decreased gluconeogenesis or other metabolic changes.

Biochemical adaptation of rat liver in response to marginal oxygen toxicity.

1. Hepatic glucose 6-phosphate dehydrogenase activity was increased in rats exposed to 5lb/in(2) (equivalent to 27000ft), 100% O(2) when compared with control animals in a 14.7lb/in(2) (sea level), air environment. Glyceraldehyde 3-phosphate dehydrogenase, isocitrate dehydrogenase, and succinate dehydrogenase were not affected by the 5lb/in(2), 100% O(2) environment. 2. Animals exposed to the hyperoxic environment consumed food, expired CO(2) and gained weight at the same rate as normoxic control animals. Additionally, blood glucose and liver glycogen concentrations were unchanged in the hyperoxic animals. The only readily apparent physiological difference in the hyperoxic animals was a decreased haematocrit. 3. The increase in glucose 6-phosphate dehydrogenase was eliminated by the injection of actinomycin D or cycloheximide. 4. Expiration of (14)CO(2) from [1-(14)C]glucose was approximately the same in hyperoxic and normoxic rats. However, (14)CO(2) expiration from [6-(14)C]glucose was markedly decreased in the animals exposed to the hyperoxic environment. 5. Calculations of the relative importance of the pentose phosphate pathway versus the tricarboxylic acid cycle plus glycolysis indicated that the livers from animals in the 5lb/in(2), 100% O(2) environment metabolized twice as much carbohydrate by way of the pentose phosphate pathway as did those from the sea-level air control animals. 6. In livers of rats exposed to 5lb/in(2), 100% O(2) the concentrations of pyruvate, citrate and 2-oxoglutarate were increased, that of isocitrate was slightly elevated, whereas the concentrations of succinate, fumarate and malate were decreased. 7. An inactivation of both tricarboxylic acid cycle lipoate-containing dehydrogenases, pyruvate and 2-oxoglutarate, under hyperoxic conditions is proposed. 8. The adaptive significance of the induction of glucose 6-phosphate dehydrogenase and the resultant production of NADPH under hyperoxic conditions is discussed.

Degradation of glucose 6-phosphate dehydrogenase into enzymatically active molecular forms by trypsin.

One of the hepatic glucose 6-phosphate dehydrogenase isozymes of rats, designated "C," has been degraded by tryptic digestion into two enzymatically active forms of different electrophoretic mobility. The modified forms exhibited the same substrate specificity and mobility as the isozymes previously designated E and E'. The results of the present study emphasized that zymograms of tissues rich in proteinases should be interpreted with caution.

Factors involved in changes in hepatic lipogenesis during development of the rat.

1. Changes in the activities of acetyl-CoA carboxylase (EC 6.4.1.2), phosphofructokinase (EC 2.7.1.11), aldolase (EC 4.1.2.13), extramitochondrial aconitate hydratase (EC 4.2.1.3) and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) have been measured in the livers of developing rats from late foetal life to maturity. 2. The effect of altering the weaning time on some enzymes associated with lipogenesis has been studied. Weaning rats at 15 days of age instead of 21 days results in an immediate increase in the activity of ;malic' enzyme (EC 1.1.1.40) whereas the activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and ATP citrate lyase (EC 4.1.3.8) did not increase until 4-5 days and acetyl-CoA carboxylase 2-3 days after early weaning. Weaning rats on to an artificial-milk diet led to complete repression of the rise in activity of hepatic enzymes associated with lipogenesis normally found on weaning, except for ;malic' enzyme, which increased in activity after 20 days of age. 3. The effect of intraperitoneal injections of glucagon, cortisol, growth hormone and thyroxine on the same hepatic enzymes has been investigated. Only thyroxine had any effect on enzyme activities and caused a 20-fold increase in ;malic' enzyme activity and a twofold increase in ATP citrate lyase activity. 4. The activities of hepatic glucose 6-phosphate dehydrogenase and ;malic' enzyme are higher in adult female than in adult male rats and it has been shown that this sex difference in enzyme activities is due to both male and female sex hormones. 5. Hepatic malate, citrate, pyruvate, glucose 6-phosphate and phosphoenolpyruvate concentrations have been measured throughout development. 6. The results are discussed in relation to the dietary and hormonal control of hepatic enzyme activities during development.

In vivo Fatty Acid and Cholesterol Synthesis in Fasted and Fasted-refed Chicks

The effects of fasting and refeeding following a fast on in vivo hepatic fatty acid and cholesterol synthesis were studied in growing chicks. Also investigated was the influence of these treatments on liver lipid and glycogen content and on the activities of hepatic glucose 6-phosphate and 6-phosphogluconate dehydrogenases and malic enzyme. Hepatic fatty acid and cholesterol synthesis were significantly depressed by a 24-hour fast and continued to decrease during the 3-day starvation period studied. Fatty acid synthesis increased to 275% and 364% of normal after 1 and 2 days of refeeding, respectively, following a 3-day fast. On day 3 of refeeding, fatty acid synthesis returned to normal and remained so throughout the remainder of the 5-day refeeding period. Cholesterol synthesis remained depressed until day 3 of refeeding, when a significant increase was observed, and reached near-normal values on day 4. The activity of the pentose pathway dehydrogenases was very low in chick liver and was not greatly influenced by fasting or refeeding. Malic enzyme activity was severely decreased by fasting and returned to control values after 2 days of refeeding. Liver weight and liver glycogen decreased markedly during the fasting period, increased to above normal values during the first 2 days of refeeding and returned to control levels after 3 days of refeeding. Liver total lipid was not significantly influenced by fasting but increased upon refeeding and began to decrease after 3 days of refeeding. Liver cholesterol content increased during fasting and decreased rapidly upon refeeding.

Effect of Feeding and of DDT on the Activity of Hepatic Glucose 6-Phosphate Dehydrogenase in Two Salmonids

The specific activity of liver glucose 6-phosphate dehydrogenase in yearling rainbow trout remained unchanged when the fish were starved for periods as long as 8 weeks and when starved animals were fed diets of various compositions. Injection of insulin concurrently with refeeding also failed to alter the specific activity of the enzyme in trout. The absence of a dietary or insulin influence on the teleost enzyme system is to be contrasted with studies in mammals in which the activity of hepatic glucose 6-P dehydrogenase was markedly stimulated after refeeding starved animals or injection of insulin.Ingestion of the pesticide DDT by juvenile coho salmon or adult rainbow trout also had no effect on the specific activity of liver glucose 6-P dehydrogenase and DDT failed to inhibit the rainbow trout enzyme in vitro. These results also differ considerably from those found in higher animals.These results suggest that the glucose 6-P dehydrogenase enzyme in teleosts may be under a different type of regulatory control from that found in mammals.

Response of Lipogenesis to Repletion in the Pyridoxine-deficient Rat

Pyridoxine has been implicated in fat metabolism. To elucidate its role the response of lipogenetic activities in the liver and epididymal pad of deficient rats to pyridoxine administration was measured. Rats were fed a pyridoxine-deficient diet until they ceased to gain weight (40 days); they were then repleted by the subcutaneous injection of 300 μg pyridoxine·HCl/rat every day for 5 days. During repletion, diets varying in fat content (0 to 25%) were fed. The administration of the vitamin resulted in increases in the liver and epididymal glucose 6-phosphate dehydrogenase which were small in the pair-fed group and substantial in the ad libitum-fed controls. The enzyme activity was highest (five fold) in rats receiving the fat-free diet. The substitution of starch for sucrose resulted in lower levels of dehydrogenase acitvity. In animals fed ad libitum and repleted with the same basal diet, the liver lipids, the hepatic glucose 6-phosphate dehydrogenase activity and the extent of acetate-14C incorporation into liver lipids were high on day 2 of repletion and returned to normal levels by day 11 with a concomitant increase in carcass fat, approaching the levels in controls maintained with a pyridoxine-sufficient diet through-out the experiment. The data demonstrate that the role of pyridoxine in lipogenesis may be mediated through the increase in food intake with the repletion of the vitamin.

INTRACELLULAR DISTRIBUTION OF ELECTROPHORETICALLY DISTINCT FORMS OF HEPATIC GLUCOSE 6-PHOSPHATE DEHYDROGENASE

INTRACELLULAR DISTRIBUTION OF ELECTROPHORETICALLY DISTINCT FORMS OF HEPATIC GLUCOSE 6-PHOSPHATE DEHYDROGENASE

Hepatic adenosine triphosphate, glucose 6-phosphate, and uridine diphosphoglucose levels in fasted, adrenalectomized, and cortisol-treated rats

An investigation of the effects of tissue isolation procedures on hepatic intermediates reveals that the usual methods for killing unanesthetized rats initiate, within seconds, large losses of ATP, and increases in glucose-6-P, obscuring in vivo levels. The magnitude, time-course and some factors influencing these changes are presented. In view of these findings and the recent interest in the possibility that changes in ATP and glucose-6-P may be important in the regulation of glycogen synthesis, an evaluation of the effects of fasting, adrenalectomy, and cortisol treatment on ATP, glucose-6-P and UDP-glucose levels was undertaken, using techniques which are shown to give reliable values for these intermediates in vivo. Although fasting lowers glucose-6-P and UDP-glucose, contrary to earlier reports it has no effect on ATP. Moreover in fasting animals neither adrenalectomy nor cortisol treatment significantly alters ATP or glucose-6-P levels. It is concluded that although nutritional status may influence glycogen synthesis through alterations in glucose-6-P levels, it seems unlikely that changes in glucose-6-P or ATP levels are responsible for the decreased glycogen levels following adrenalectomy or the increase in glycogen synthesis following cortisol treatment. UDP-glucose measurements, however, confirm the conclusion of others that an early glucocorticoid action is the direct or indirect activation of the glycogen synthetase reaction, since UDP-glucose levels are increased after adrenalectomy and are decreased early during cortisol-induced glycogen synthesis.

Some Observations Concerning Hepatic Glucose 6-Phosphate Content in Normal and Diabetic Rats

Some Observations Concerning Hepatic Glucose 6-Phosphate Content in Normal and Diabetic Rats

Effect of hypoglycin A on liver glycogen with a method for the study of changes in liver glycogen.

ARTICLESEffect of Hypoglycin A on Liver Glycogen With a Method for the Study of Changes in Liver GlycogenSydney J. PatrickSydney J. PatrickPublished Online:01 Sep 1954https://doi.org/10.1152/jappl.1954.7.2.140MoreSectionsPDF (536 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInvestigation of hepatic ATP and glucose 6-phosphate as indices of hypoglycin toxicityBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 297, No. 1The effects of hypoglycin-A, a leucine analogue, on the development of rat and chick embryosLife Sciences, Vol. 9, No. 22Metabolic effects of hypoglycin and methylenecyclopropaneacetic acidBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 125, No. 1Metabolism and metabolic effects of hypoglycinBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 90, No. 3Effects of hypoglycin on certain aspects of glucose and fatty acid metabolism in the ratBiochemical Pharmacology, Vol. 3, No. 4 More from this issue > Volume 7Issue 2September 1954Pages 140-142 https://doi.org/10.1152/jappl.1954.7.2.140PubMed13211486History Published online 1 September 1954 Published in print 1 September 1954 Metrics