Nutritional and hormonal regulation of the activity state of hepatic branched-chain alpha-keto acid dehydrogenase complex.
The hepatic branched-chain alpha-keto acid dehydrogenase complex plays an important role in regulating branched-chain amino acid levels. These compounds are essential for protein synthesis but are toxic if present in excess. When dietary protein is deficient, the hepatic enzyme is present in the inactive, phosphorylated state to allow conservation of branched-chain amino acids for protein synthesis. When dietary protein is excessive, the enzyme is in the active, dephosphorylated state to commit the excess branched-chain amino acids to degradation. Inhibition of protein synthesis by cycloheximide, even when the animal is starving for protein, results in activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex to prevent accumulation of branched-chain amino acids. Likewise, the increase in branched-chain amino acids caused by body wasting during starvation and uncontrolled diabetes is blunted by activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex. The activity state of the hepatic branched-chain alpha-keto acid dehydrogenase complex is regulated in the short term by the concentration of branched-chain alpha-keto acids (inhibitors of branched-chain alpha-keto acid dehydrogenase kinase) and in the long term by alteration in the total branched chain alpha-keto acid dehydrogenase kinase activity.
Harris
R A
RA
Department of Biochemistry, Indiana University School of Medicine, Indianapolis 46223.
Goodwin
G W
GW
Paxton
R
R
Dexter
P
P
Powell
S M
SM
Zhang
B
B
Han
A
A
Shimomura
Y
Y
Gibson
R
R
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004044:Dietary Proteins / Q000494:pharmacology; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D009747:Nutritional Physiological Phenomena; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013217:Starvation
D004044:Dietary Proteins; D009097:Multienzyme Complexes; D003513:Cycloheximide; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)