Hyperthyroidism results in increased glycolytic capacity in the rat heart. A 31P-NMR study

AML Seymour, H Eldar, GK Radda - Biochimica et Biophysica Acta (BBA) …, 1990 - Elsevier
AML Seymour, H Eldar, GK Radda
Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1990Elsevier
We have investigated the metabolic adaptations that occur in the thyroxine-treated rat heart.
Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 μg/100 g
body weight) over seven days. 31 P-NMR investigations of isolated glucose-perfused
isometric hearts showed that thyroxine treatment caused an increase in P i (from 4.9 μmol·(g
dry wt.)− 1 in control hearts to 11.7 μmol·(g dry wt.)− 1 in hyperthyroid hearts), a decrease in
phosphocreatine (from 36.5 μmol·(g dry wt.)− 1 to 21.8 μmol·(g dry wt.)− 1) with no change in …
Abstract
We have investigated the metabolic adaptations that occur in the thyroxine-treated rat heart. Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 μg/100 g body weight) over seven days. 31P-NMR investigations of isolated glucose-perfused isometric hearts showed that thyroxine treatment caused an increase in Pi (from 4.9 μmol · (g dry wt.)−1 in control hearts to 11.7 μmol · (g dry wt.)−1 in hyperthyroid hearts), a decrease in phosphocreatine (from 36.5 μmol · (g dry wt.)−1 to 21.8 μmol · (g dry wt.)−1) with no change in ATP or ADP concentrations under the same conditions of cardiac work. The unidirectional exchange flux Pi → ATP was measured by saturation transfer NMR in hyperthyroid rat hearts. This exchange (which has been shown to contain a significant glycolytic component) increased by 2.2-fold in thyroxine-treated hearts in comparison to control hearts (to 3.6 μmol · (g dry wt.)−1 · s−1, from 1.6 μmol · (g dry wt.)−1 · s−1). In parallel experiments, NMR analysis of extracts from hyperthyroid rat hearts showed significantly elevated levels of glucose 6-phosphate, and fructose 6-phosphate. Measurements of enzyme activities isolated from hyperthyroid and control tissue showed a 40% increase in phosphofructokinase activity. These data together with the increased concentration of Pi show that both glycolytic and glycogenolytic fluxes are increased in the hyperthyroid rat heart. This metabolic adaptation may be necessary to cope with the increased number and activity of Na+/K+-ATPase pumps that occur in response to thyroxine treatment.
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