IN VITROACTION OF THYROXINE ANALOGS ON SUCCINATE AND MALATE OXIDATION1

Abstract

A critical discussion of in vitro responses to thyroxine, especially of their supposed relation to in vivo mechanism of action of the hormone is presented. The point is stressed that for an in vitro response to be of value in interpreting in vivo function, it must be specific at least to the extent of not being altered by thyroxine analogs which are inactive in vivo. This is here illustrated by the in vitro thyroxine enhancement of succinoxidase and depression of malic dehydrogenase. Even if thyroxine''s metabolic action in vivo should depend upon an increased succinoxidase activity, it cannot act this way for 2 reasons first, thyroxine analogs which have no metabolism-stimulating action in the intact animal produce as much effect on enhancing succinate oxidation and in depressing malate oxidation. Secondly, if thyroxine is to stimulate oxidations in an overall fashion, a highly unphysiological situation would be presented by a succinoxidase stimulated only by a depression in malic dehydrogenase, since it should be necessary for the body to handle increased amounts of malate resulting from the oxidation of succinate.