Experimental hyperthyroidism causes inactivation of the branched-chain alpha-ketoacid dehydrogenase complex in rat liver.
Hyperthyroidism induced by 3-day treatment of rats with thyroid hormone (T(3); 3,5,3'-triiodothyronine) at 0.1 or 1 mg/kg body wt/day resulted in a reduced activity state (% of enzyme in its active, dephosphorylated state) of the hepatic branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. One treatment with 0.1 mg T(3)/kg body wt caused a significant effect on the activity state of BCKDH complex after 24 h, indicating that the reduction of the activity state was triggered by the first administration of T(3). Hyperthyroidism also caused a stable increase in BCKDH kinase activity, the enzyme responsible for phosphorylation and inactivation of the BCKDH complex, suggesting that T(3) caused inactivation of the BCKDH complex by induction of its kinase. Western blot analysis also revealed increased amounts of BCKDH kinase protein in response to hyperthyroidism. No change in the plasma levels of branched-chain alpha-keto acids was observed in T(3)-treated rats, arguing against an involvement of these known regulators of BCKDH kinase activity. Inactivation of the hepatic BCKDH complex as a consequence of overexpression of its kinase may save the essential branched-chain amino acids for protein synthesis during hyperthyroidism.
Kobayashi
R
R
Department of Biochemistry, Indiana University School of Medicine, Indianapolis, Indiana, 46202-5122, USA.
Shimomura
Y
Y
Otsuka
M
M
Popov
K M
KM
Harris
R A
RA
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D001835:Body Weight / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006980:Hyperthyroidism / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D007651:Keto Acids / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology; D009929:Organ Size / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013217:Starvation / Q000201:enzymology / Q000503:physiopathology; D014284:Triiodothyronine / Q000097:blood
D007651:Keto Acids; D009097:Multienzyme Complexes; D014284:Triiodothyronine; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase