ABSTRACT
The levels of activity of some enzymes involved in oxidative metabolism have been determined in left ventricular tissue from spontaneously hypertensive rats compared with those in normotensive controls. Levels of pyruvate kinase were increased about 1.3 fold indicative of elevated glycolytic activity. Similarly, enhanced levels of lactate dehydrogenase were found, consistent with a requirement for increased oxidation of cytosolically-generated NADH. In addition a more active malate-aspartate shuttle, which in heart provides the major route for transfer of reducing equivalents to the mitochondria, was suggested by elevated levels of the cytosolic isoenzyme of aspartate aminotransferase; malate dehydrogenase did not increase but the activity of this enzyme is very high and unlikely to be rate-limiting in the shuttle. The levels of expression of mRNAs for three of these enzymes (pyruvate kinase, aspartate aminotransferase and malate dehydrogenase) were also determined and correlated well with the extent of change, if any, in the changes in enzymatic activity. Thus it seems that one response to development of hypertension in rats is an increase in expression of the genes for certain key enzymes involved in oxidative metabolism.
Subject(s)
Aspartate Aminotransferases/metabolism , Heart Ventricles/enzymology , Hypertension/enzymology , L-Lactate Dehydrogenase/metabolism , Malate Dehydrogenase/metabolism , Pyruvate Kinase/metabolism , Animals , Biological Transport , Cytosol/metabolism , Glycolysis , Male , Mitochondria, Heart/metabolism , Oxidation-Reduction , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
Little is known about control of expression of basal levels of the aspartate aminotransferases which are ubiquitous 'house keeping' enzymes in vertebrates. We have measured both mRNA and activity levels for both isoenzymes in various rat tissues as a function of age. Patterns of mRNA expression for the two isoenzymes were similar in a particular tissue about differed widely between tissues. Surprisingly, there was no simple correlation between mRNA levels and specific activities of the enzyme products. We conclude that translation for mRNA for these two isoenzymes is subject to tissue-specific, and in some cases age-related, regulation.
