Increased Pyruvate Kinase Activity Research Articles

A biochemical basis for differences in maximal diving time in aquatic mammals

1. 1. Pyruvate kinase activities and cytochrome oxidase activities in five tissues (heart, brain, skeletal muscle, liver, lung) were measured in three species of diving mammals (sea lion, harbor seal, Weddell seal) with widely varying maximal diving times. 2. 2. There was increased pyruvate kinase activity in heart and brain with increasing maximal diving times. 3. 3. This suggests that enhanced glycolysis as reflected in increased pyruvate kinase activities may be important in permitting cell survival in the face of prolonged O 2 depletion. 4. 4. No similar relation was found with respect to cytochrome oxidase activity. 5. 5. The biosynthesis of key glycolytic enzymes may be geared to an increasing requirement for ATP generated by anaerobic glycolysis in aquatic mammals.

Adaptations of energy metabolism in the cultivated macrophage.

Adaptive changes in energy metabolism, as reflected by pyruvate kinase and cytochrome oxidase activities, were examined during in vitro differentiation of the cultivated macrophage. Serum concentrations of tissue culture media, which directly influence endocytic activity, and ambient oxygen tension were both shown to influence pyruvate kinase and cytochrome oxidase activities. Cells maintained in high serum concentrations (30% newborn calf serum [NBCS]) exhibited a 300-400% increase in pyruvate kinase activity and a 40% increase in cytochrome oxidase activity, whereas cells maintained in low serum concentrations (2% NBCS) exhibited a lesser increase (65%) in pyruvate kinase activity and no change in cytochrome oxidase activity. Anaerobiosis resulted in additional alterations in pyruvate kinase and cytochrome oxidase activities. Cells maintained for 48-72 h under anaerobic conditions exhibited a 500-600% increase in pyruvate kinase activity and a 40% decrease in cytochrome oxidase activity. Increased pyruvate kinase activity was dependent on continued protein synthesis. Enzyme increases occurred in anaerobically cultured cells despite an overall reduction in cell protein synthesis. It is suggested that adaptive changes in pyruvate kinase and cytochrome oxidase activity resulting from alterations in either serum concentration or ambient oxygen tension are regulated by two independent mechanisms. One mechanism is aimed at providing energy for endocytic activity and the other in compensating for impaired oxidative metabolism during anaerobiosis.

Effect of endotoxin on pyruvate kinase activity in mouse liver.

The pyruvate kinase (PK) activity of mouse liver increases after injection of endotoxin. It decreases in animals given cortisone alone and remains essentially unchanged in those given cortisone and endotoxin at the same time. CCl(4) causes an increase in liver PK activity, but neither it nor endotoxin changes the activity of muscle PK. Addition of octonoate to liver homogenates inhibits the activity of liver PK. These results suggest that the rapid depletion in liver glycogen after administration of endotoxin or CCl(4) may be related to increased PK activity. Induction of tolerance does not prevent the increase in liver PK activity in challenged animals.

Dietary Regulation of Pyruvate Kinase Synthesis in Rat Liver

The effects of diet and antibiotics on pyruvate kinase, glucose 6-phosphatase and tyrosine-α-ketoglutarate transaminase activities were investigated in male Sprague-Dawley rats. Feeding a 90% casein diet to animals pre-fed with a 90% carbohydrate diet for 4 days increased the activities of all 3 enzymes. Force-feeding with casein hydrolysate increased glucose 6-phosphatase, tyrosine-α-ketoglutarate transaminase and pyruvate kinase activity, though the latter increase was observable only in the animals pre-fed with glucose. The increase in glucose 6-phosphatase activity was partially prevented by actinomycin D and almost totally prevented by cycloheximide. The increase in pyruvate kinase activity (in the animals pre-fed with glucose) was not affected by actinomycin D, but was prevented by cycloheximide. Both antibiotics increased tyrosine-α-ketoglutarate transaminase activity far beyond the increase caused by force-feeding casein hydrolysate alone. 8-Azaguanine decreased the induction of glucose 6-phosphatase by force-feeding casein hydrolysate without inducing tyrosine-α-ketoglutarate transaminase or decreasing the induction of the transaminase by actinomycin D or cyclohexamide. Pyruvate kinase activity was induced by force-feeding carbohydrate to rats pre-fed for 5 days with a 90% casein diet. These increases were prevented by both actinomycin D and cycloheximide. Tyrosine-α-ketoglutarate transaminase was not induced by the antibiotics in these animals. Generally, enzyme activities were higher in the animals pre-fed with fructose, even after force-feeding. The results are in agreement with those for an earlier proposed mechanism of control for the synthesis of pyruvate kinase; that is, the synthesis of this enzyme is controlled at the translational level when the dietary change is from a protein-free to a high protein diet and at the transcriptional level in the case of the high protein to protein-free dietary change.

The Effect of Insulin on Enzyme Adaptations to Diets and Hormones

Abstract 1. Insulin prevented increases in liver glucose 6-phosphatase and fructose 1,6-diphosphatase activities in response to cortisol administration, but it did not prevent increases in response to diets high in protein or in fructose. 2. Insulin increased pyruvate kinase activity in animals treated with cortisol or fed a high protein diet; both treatments decrease pyruvate kinase activity. Insulin did not increase the pyruvate kinase activity of animals receiving a high glucose diet. 3. Insulin administration had a more marked effect on glucose 6-phosphate dehydrogenase activity than on malic dehydrogenase (decarboxylating) activity. 4. The increases in serine dehydrase, glutamic-oxalacetic transaminase, and malic dehydrogenase in response to cortisol treatment were partially or completely prevented by insulin. The increases in glutamic-pyruvic transaminase and lactic dehydrogenase in response to cortisol administration were not affected by insulin. Insulin either had no effect on increases observed in these enzymes after high protein or high fructose feeding or caused even greater increases after dietary treatment. Two enzymes (glutamic-pyruvic transaminase and lactic dehydrogenase) not affected by insulin in the glucose-fed group were increased by insulin in groups receiving high protein or high fructose diets.

INSULIN: INDUCER OF PYRUVATE KINASE.

The hepatic pyruvate kinase activity markedly decreased when rats were made diabetic by alloxan injection. Insulin treatment induced new synthesis of pyruvate kinase which was prevented by injection of ethionine and actinomycin D. The evidence indicated that the increased pyruvate kinase activity induced by inisulin entails at a certain stage a stimulation of the synthesis of certain RNA species relevant to the production of this enzyme.