Tissue-specific responses of branched-chain alpha-ketoacid dehydrogenase activity in metabolic acidosis.
In adrenalectomized rats, acidosis does not increase whole-body leucine oxidation unless a physiologic amount of glucocorticoids (dexamethasone) is also provided; an equivalent dose of dexamethasone without acidosis does not change leucine catabolism. Because the influences of acidification and glucocorticoids on branched-chain amino acid metabolism in specific organs are unknown, the function of branched-chain alpha-ketoacid dehydrogenase (BCKAD), the rate-limiting enzyme in branched-chain amino acid catabolism, in adrenalectomized rat skeletal muscle and liver, the two major tissues that degrade branched-chain amino acid was measured. In muscle of acidotic adrenalectomized rats receiving dexamethasone, basal and total BCKAD activities were increased 2.6- (P < 0.05) and 2.8-fold (P < 0.05), respectively. Neither acidosis nor dexamethasone alone increased these activities. BCKAD E1alpha subunit mRNA in muscle of acidotic rats given dexamethasone was increased 1.89-fold (P < 0.05) in parallel with the change in BCKAD activity; BCKAD E2 subunit mRNA was increased by acidosis, dexamethasone, or a combination of both stimuli. In contrast, basal BCKAD activity in liver of rats with acidosis or dexamethasone was nearly threefold lower (P < 0.05) and changes in enzyme activity reflected reduced subunit mRNA. Thus, there are reciprocal, tissue-specific changes in BCKAD function in response to acidosis.
Renal Division, Emory University, Atlanta, Georgia 30322, USA.
S R
SR
Price
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Wang
J L
JL
Bailey
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000138:Acidosis / Q000201:enzymology*; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D003907:Dexamethasone; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)