1. Gluconeogenesis from lactate or pyruvate was studied in perfused livers from starved rats at perfusate pH7.4 or under conditions simulating uncompensated metabolic acidosis (perfusate pH6.7-6.8). 2. In ‘acidotic’ perfusions gluconeogenesis and uptake of lactate or pyruvate were decreased. 3. Measurement of hepatic intermediate metabolites suggested that the effect of acidosis was exerted at a stage preceding phosphoenolpyruvate. 4. Total intracellular oxaloacetate concentration was significantly decreased in the acidotic livers perfused with lactate. 5. It is suggested that decreased gluconeogenesis in acidosis is due to substrate limitation of phosphoenolypyruvate carboxykinase. 6. The possible reasons for the fall in oxaloacetate concentration in acidotic livers are discussed; two of the more likely mechanisms are inhibition of the pyruvate carboxylase system and a change in the [malate]/[oxaloacetate] ratio due to the fall in intracellular pH.
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April 1977
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Research Article|
April 15 1977
The mechanism of inhibition by acidosis of gluconeogenesis from lactate in rat liver
Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1977 London: The Biochemical Society
1977
Biochem J (1977) 164 (1): 185–191.
Citation
R A Iles, R D Cohen, A H Rist, P G Baron; The mechanism of inhibition by acidosis of gluconeogenesis from lactate in rat liver. Biochem J 15 April 1977; 164 (1): 185–191. doi: https://doi.org/10.1042/bj1640185
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