Open AccessBicarbonate and the Pathway of Glutamate Oxidation in Isolated Rat‐Liver Mitochondria
Author(s) -
WANDERS Ronald J. A.,
MEIJER Alfred J.,
GROEN Albert K.,
TAGER Joseph M.
Publication year - 1983
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1983.tb07455.x
Subject(s) - transamination , bicarbonate , glutamate dehydrogenase , deamination , chemistry , biochemistry , glutamate receptor , glutamate synthase , pyruvate dehydrogenase complex , ammonia , enzyme , organic chemistry , receptor
1 The factors affecting the pathway of glutamate oxidation were studied in isolated rat‐liver mitochondria in incubations of 2–3 min. 2 It was found that bicarbonate at a physiological concentration has a profound effect on the pathway of glutamate oxidation. Ammonia formation via glutamate dehydrogenase is stimulated by bicarbonate [from 5.48 ± 0.29 ( n = 10) to 9.57 ± 0.73 ( n = 8) nmol ± min −1 ± mg protein −1 ], whereas aspartate formation via the transamination pathway is inhibited [from 38.41 ± 2.24 ( n = 9) to 24.56 ± 3.28 ( n = 6) nmol ± min −1 ± mg protein −1 ]. 3 Bicarbonate has no effect on the rate of transport of glutamate via the glutamate‐hydroxyl translocator. 4 The interaction of bicarbonate with the pathway of glutamate oxidation occurs primarily at the level of succinate dehydrogenase, due to competitive inhibition of the enzyme by bicarbonate. 5 Inhibition by bicarbonate of the transamination pathway leads to a decrease in intramitochondrial 2‐oxoglutarate, so that the deamination pathway is stimulated. 6 Using an equation which describes flux through glutamate dehydrogenase kinetically, it could be shown that the bicarbonate‐induced decrease in intramitochondrial 2‐oxoglutarate quantitatively accounts for the enhanced rate of deamination. 7 It is concluded that in the intact liver flux through glutamate dehydrogenase is sufficient to account for the ammonia formation required for urea synthesis from substrates such as alanine.