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PMID:4353083

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Citation

Wimhurst, JM and Manchester, KL (1973) Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate. Biochem. J. 134:143-56

Abstract

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.

Links

PubMed PMC1177795

Keywords

Animals; Cycloheximide/pharmacology; Enzyme Induction/drug effects; Enzyme Repression/drug effects; Fructose/pharmacology; Fructose-Bisphosphatase/metabolism; Glucokinase/metabolism; Gluconeogenesis/drug effects; Glucose/pharmacology; Glucose-6-Phosphatase/metabolism; Glycolysis/drug effects; Hexokinase/metabolism; L-Serine Dehydratase/metabolism; Lactates/pharmacology; Ligases/metabolism; Liver/drug effects; Liver/enzymology; Male; Perfusion; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism; Phosphofructokinase-1/metabolism; Pyruvate Kinase/metabolism; Pyruvates; Rats; Starvation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:B2RYG2

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:B2RYG2

enables

GO:0004611: phosphoenolpyruvate carboxykinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:F1LQJ7

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:F1LQJ7

enables

GO:0004611: phosphoenolpyruvate carboxykinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:PCKGC

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PCKGC

enables

GO:0004611: phosphoenolpyruvate carboxykinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:KPYR

involved_in

GO:0006096: glycolytic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:KPYR

enables

GO:0004743: pyruvate kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:F16P1

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:F16P1

enables

GO:0042132: fructose 1,6-bisphosphate 1-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:PFKAL

involved_in

GO:0006096: glycolytic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:G6PC1

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:G6PC1

enables

GO:0004346: glucose-6-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:G6PC3

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:G6PC3

enables

GO:0004346: glucose-6-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:F16P2

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:F16P2

enables

GO:0042132: fructose 1,6-bisphosphate 1-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:HXK4

enables

GO:0004340: glucokinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:HXK4

involved_in

GO:0006096: glycolytic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:HXK1

enables

GO:0004396: hexokinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:HXK1

involved_in

GO:0006096: glycolytic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PYC

enables

GO:0004736: pyruvate carboxylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:PYC

involved_in

GO:0006094: gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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