Inhibition of Pyruvate Dehydrogenase during the Metabolism of Glutamine and Proline in Hemoglobin‐Free Perfused Rat Liver

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Abstract

A shift of pyruvate dehydrogenase from the active (dephospho) towards the inactive (phospho) form results from the metabolism of added glutamine in isolated perfused rat liver. This is evidenced by a decreased release of 14CO2 from [1‐14C]pyruvate and by direct measurement of enzyme activity in the freeze‐stopped liver tissue. Half‐maximal glutamine concentration for the inhibition of pyruvate oxidation is about 1 mM, i.e. within the physiological range. The effect is reversible and exhibits a time course similar to that of glutamine metabolism as measured by the production of ammonia and urea. The effect is independent of the mode of glutaminase activation, either by ammonium ions or glucagon or by so‐called ‘self‐activation’. When oxoglutarate, glutamate and ammonia are generated intracellularly from proline, there is also an inhibition of 14CO2 release from [1‐14C]pyruvate. Proline metabolism is stimulated about twofold by addition of glucagon. This is accompanied by a further decrease of pyruvate dehydrogenase activity, whereas addition of glucagon alone has no effect. There is good agreement between 14CO2 production from [1‐14C]glutamine and oxoglutarate production as calculated from nitrogen balance measurements. This indicates that oxoglutarate formed from glutamine is predominantly oxidized by oxoglutarate dehydrogenase. Furthermore, there is a close correlation between oxidation of oxoglutarate derived from glutamine or proline and the degree of inhibition of pyruvate dehydrogenase. This correlation holds also when oxoglutarate production from glutamine or proline is increased by ammonium ions or glucagon. Thus, it is concluded that increased flux through oxoglutarate dehydrogenase is accompanied by a decreased flux through pyruvate dehydrogenase in rat liver. Copyright © 1982, Wiley Blackwell. All rights reserved

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CITATION STYLE

APA

HÄUSSINGER, D., GEROK, W., & SIES, H. (1982). Inhibition of Pyruvate Dehydrogenase during the Metabolism of Glutamine and Proline in Hemoglobin‐Free Perfused Rat Liver. European Journal of Biochemistry, 126(1), 69–76. https://doi.org/10.1111/j.1432-1033.1982.tb06747.x

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