Ketone-body metabolism in hyperthyroid rats: reduced activity of D-3-hydroxybutyrate dehydrogenase in both liver and heart and of succinyl-coenzyme A: 3-oxoacid coenzyme A-transferase in heart.
The specific activity of D-3-hydroxybutyrate dehydrogenase is reduced by about a third in liver and heart mitochondria of hyperthyroid rats. State 3 respiration is also reduced in isolated mitochondria from the same animals when DL-3-hydroxybutyrate is the substrate. Determination of the kinetic parameters of the membrane-bound D-3-hydroxybutyrate dehydrogenase in liver of hyperthyroid rats reveals a decreased in maximal velocity (Vmax). The Michaelis and dissociation constants of NAD+ and D-3-hydroxybutyrate are also significantly influenced, thus indicating that both the affinity and the binding of this enzyme toward its substrates are affected. In hyperthyroid rats a significant ketone-body increase is found in both liver and heart: in blood, an almost doubled concentration can be measured. At the same time, in heart mitochondria of these animals the activity of succinyl-coenzyme A: 3-oxoacid coenzyme A-transferase is significantly reduced. The decrease in both D-3-hydroxybutyrate dehydrogenase and 3-oxoacid coenzyme A-transferase associated with the increase in ketone bodies supports the suggestion that there is a lower utilization of these compounds by peripheral tissues. In the blood of hyperthyroid rats a higher D-3-hydroxybutyrate/acteoacetate ratio is also found, probably resulting from a selective utilization of the two compounds in this pathological state.
Research Unit on Mitochondria and Energy Metabolism, CNR, Bari, Italy.
R
R
Lippolis
N
N
Altamura
C
C
Landriscina
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D015256:Coenzyme A-Transferases; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006884:Hydroxybutyrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006980:Hyperthyroidism / Q000201:enzymology*; D007657:Ketone Bodies / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013367:Submitochondrial Particles / Q000201:enzymology
D000214:Acyl Coenzyme A; D007657:Ketone Bodies; C012046:succinyl-coenzyme A; D005993:Glycerolphosphate Dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; C036140:L-alpha-glycerol-phosphate oxidase; D000217:Acyltransferases; D015256:Coenzyme A-Transferases