Abstract #1881
The Effects of Acute and Chronic Up-Regulation of Pyruvate Dehydrogenase on Myocardial Metabolism
Lucia F Giles 1 , Vicky Ball 1 , and Damian J Tyler 1
1
Department of Physiology, Anatomy and
Genetics, University of Oxford, Oxford, Oxfordshire,
United Kingdom
Pyruvate dehydrogenase (PDH) is a key regulatory enzyme
in cardiac metabolism and is activated by
dichloroacetate (DCA). The effects of DCA on PDH and
glycolytic flux were investigated in vivo and the
perfused heart using hyperpolarized [
13
C]pyruvate
and [
3
H]glucose. PDH flux was enhanced in
vivo following acute and chronic DCA treatment. This was
accompanied by a decrease in glycolytic flux and lactate
production despite the increase in PDH flux. This
suggests that either glucose is oxidised more
efficiently when coupling between glycolysis and glucose
oxidation is enhanced or that increased glucose
oxidation leads to inhibition of glycolysis via a
negative feedback pathway.
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