Metabolic acidosis accelerates whole body protein degradation and leucine oxidation by a glucocorticoid-dependent mechanism.
Previous work documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheterized, awake, male Sprague-Dawley rats using stochastic modeling and a primed continuous infusion of L[1-14C] leucine. Whole body protein turnover was accelerated by acidosis as reflected in a 70% increase in proteolysis and a 55% increase in protein synthesis. Amino acid oxidation was increased by 145% in rats with acidosis relative to control rats receiving diets identical in protein and calories based on a reciprocal pool model and plasma alpha-ketoisocaproate specific radioactivity. These changes were accompanied by a 104% increase in liver branched-chain ketoacid dehydrogenase (BCKAD) activity in rats with acidosis, similar to previously documented increases in skeletal muscle BCKAD activity caused by acidosis. In contrast, kidney BCKAD activity was decreased by 38%, illustrating the tissue specificity of the changes that were present. We conclude that chronic metabolic acidosis accelerates whole body protein turnover and reduces the efficiency of protein utilization by accelerating amino acid oxidation. These changes may require an intact glucocorticoid axis.
May
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RC
Renal Division, Emory University School of Medicine, Atlanta, Ga.
Masud
T
T
Logue
B
B
Bailey
J
J
England
B K
BK
D000138:Acidosis / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005938:Glucocorticoids / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D005938:Glucocorticoids; D011506:Proteins; D007930:Leucine