Allosteric inhibition of muscle pyruvate kinase by phenylalanine

Asúa, Luis Jiménez de; Carminatti, Héctor

doi:10.1016/0014-5793(70)80549-x

Cited by 22 publications

(8 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main isoenzyme in liver, the L-type isoenzyme (for a review see Engstr6m, 1978), is subject to a complex pattern of regulation. The enzyme shows co-operative binding of phosphoenolpyruvate (Rozengurt et al, 1969) and is subject to regulation by a number of allosteric ligands, including fructose 1,6-bisphosphate Ekman et al, 1976) and alanine (Seubert et al, 1968). All of these processes are in turn influenced by the fact that the enzyme is susceptible to phosphorylation by cyclic AMPdependent protein kinase (Ljungstrom et al, 1974; Abbreviation used: SDS, sodium dodecyl sulphate.…”

mentioning

confidence: 99%

Biosynthesis of rat liver pyruvate kinase. Measurement of enzyme lifetime and the rate of synthesis at weaning

Hopkirk¹,

Bloxham²

1980

Biochemical Journal

View full text Add to dashboard Cite

Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of immunoprecipitates of liver cytosol with anti-(L-type pyruvate kinase) serum revealed proteins of mol.wt. 56 000 and 42 000 in addition to the heavy and light chains. The ratio of the 56 000 mol.wt. to the 42 000 mol.wt. protein increased under dietary conditions that resulted in an increase in the apparent specific activity of hepatic pyruvate kinase. The 42 000 mol.wt. protein was removed from immunoprecipitates if the liver cytosol was partially purified by pH precipitation and (NH4)2SO4 fractionation before addition of the antiserum. This technique may be used to analyse the formation of pure L-type pyruvate kinase in liver. By using H14CO3-labelling, the t1/2 of L-type pyruvate kinase was estimated as 75 +/- 1.7 h in post-weaned high-carbohydrate-diet-fed rats. Before weaning there was little immunoreactive pyruvate kinase in rat liver cytosol. Induction began between 6 and 24 h after weaning and reached a maximum value 120 h after weaning. When clearly enhanced total pyruvate kinase activity was first observed at 24 h post-weaning, the apparent specific activity of hepatic pyruvate kinase was considerably lower than the specific activity of the pure isolated enzyme. When the induction of L-type pyruvate kinase was monitored by the incorporation of L-[4,5-3H]leucine, the maximum rate of synthesis occurred 24--48 h after weaning. After this period synthesis declined, indicating a relatively slow turnover of the enzyme once the enzyme concentration was established in the liver.

show abstract

mentioning

confidence: 99%

Biosynthesis of rat liver pyruvate kinase. Measurement of enzyme lifetime and the rate of synthesis at weaning

Hopkirk¹,

Bloxham²

1980

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…significant regulatory role in glycolysis (Rozengurt et al, 1969; for other pertinent references see introductory paragraph of Flory & Koeppe, 1973). It is difficult, however, to evaluate the probable physiological activity of the enzyme, or factors most important in its regulation from previously available information.…”

mentioning

confidence: 99%

Kinetic properties of rat liver pyruvate kinase at cellular concentrations of enzyme, substrates and modifiers

Flory

Peczon

Koeppe

et al. 1974

Biochemical Journal

View full text Add to dashboard Cite

Kinetic properties of rat liver pyruvate kinase type I at pH7.5 and 6.5 were studied with physiological ranges of substrates, modifiers and Mg(2+) concentrations at increasing enzyme concentrations, including the estimated cellular concentrations (approx. 0.1mg/ml). Enzyme properties appear unaffected by increased enzyme concentration if phosphoenolpyruvate, fructose 1,6-diphosphate and inhibitors are incubated with enzyme before starting the reaction with ADP. Our data suggest that minimum cellular concentrations of MgATP and l-alanine provide virtually complete inhibition of pyruvate kinase I at pH7.5. The most likely cellular control of existing pyruvate kinase I results from the strong restoration of enzyme activity by the small physiological amounts of fructose 1,6-diphosphate. Decreasing the pH to 6.5 also restores pyruvate kinase activity, but to only about one-third of its activity in the presence of fructose 1,6-diphosphate. Neither pyruvate nor 2-phosphoglycerate at cellular concentrations inhibit the enzyme significantly.

show abstract

“…Pyruvate kinase type I, which may play an important role in the control of glycolysis and gluconeogenesis, exhibits sigmoidal kinetics with phosphoenolpyruvate, allosteric activation with fructose 1,6-diphosphate and inhibi-tionbyATP (Taylor & Bailey, 1967;Carminatti etal., 1968;Susor & Rutter, 1968;Tanaka et al, 1967b). Whereas fructose 1,6-diphosphate or lower pH transforms the sigmoidal response to phosphoenolpyruvate into a hyperbolic relationship, they increase the co-operativity of the ATP inhibition (Tanaka et al, 1967b;Rozengurt et al, 1969). Inhibition by L-alanine resembles that of ATP (Llorente et al, 1970).…”

mentioning

confidence: 99%