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Phosphorylation‐Mediated Changes in Pyruvate Dehydrogenase Activity Influence Pyruvate‐Supported Calcium Accumulation by Brain Mitochondria
Author(s) -
Browning M.,
Baudry M.,
Bennett W. F.,
Lynch G.
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb10817.x
Subject(s) - pyruvate dehydrogenase complex , calcium , pyruvate decarboxylation , pyruvate dehydrogenase kinase , biochemistry , mitochondrion , pyruvate dehydrogenase phosphatase , chemistry , stimulation , biology , endocrinology , enzyme , organic chemistry
Changes in the activity of pyruvate dehydrogenase [pyruvate: lipoamide oxidoreductase (decarboxylating and acceptor‐acetylating), EC 1.2.4.1, PDH], elicited by inhibition of the phosphorylation of its 40,000 M r α‐subunit, were compared with changes in pyruvate‐supported calcium accumulation by rat brain mitochondria. Dichloroacetate (DCA) produces concentration‐dependent inhibition of the phosphorylation of intramitochondrial PDH a‐subunit, which is accompanied by stimulation of PDH activity and calcium accumulation. DCA did not affect succinate‐ or ATP‐supported mitochondrial calcium accumulation. The concentration of DCA giving half‐maximal inhibition of the phosphorylation was almost identical to that giving half‐maximal stimulation of PDH activity and calcium accumulation. PDH activity and pyruvate‐supported calcium accumulation showed similar dependence on pyruvate concentration with respective apparent affinities for pyruvate of 40 μ m and 30 μ m , and both activities exhibited positive cooperativity. DCA modified only the maximal activity of PDH or the maximal calcium accumulation without changing either the apparent affinities for pyruvate or calcium or the Hill coefficients. These data provide evidence that calcium accumulation by mitochondria is tightly linked to PDH activity and that changes in the phosphorylation of the PDH α‐subunit can be reflected in changes in the calcium‐buffering ability of mitochondria. This suggests a possible mechanism by which a variety of manipulations, such as repetitive synaptic stimulation, can alter the regulation of internal calcium levels.