STIMULATION OF RAT-LIVER BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE-ACTIVITY BY CHRONIC METABOLIC-ACIDOSIS

During chronic metabolic acidosis, the degradation of protein and amin o acids reportedly increases. Branched-chain alpha-keto acid dehydroge nase complex (BCKDH) relates amino-acid catabolism and mitochondrial-e nergy metabolism. This study was designed to evaluate the effect of ac idosis on the activity of liver BCKDH, the key regulatory enzyme in th e catabolism of branched-chain amino acids. Experimental acidosis was induced in rats by ingestion of 0.28 M ammonium chloride solution for 10 days. We made two different liver-mitochondrial extracts to assay i ndependently the active form of BCKDH and the total BCKDH activity. Ac idosis significantly increased both active and total BCKDH specific ac tivities (P < 0.05). The mean value for the active form of the BCKDH c omplex was 9.27+/-1.10 (S.E.M., n = 7) mU/mg of mitochondrial protein in acidotic rats and 5.18 +/- 0.84 (n = 7) for the control rats. The v alue of the total complex was 16.10 +/- 1.22 (n = 7) for the acidosis and 11.51 +/- 0.58 (n = 7) for the control. No significant changes wer e found in the activity stale of the complex. Citrate synthase activit y did not show significant variations between treatments. The stimulat ion of liver BCKDH activities by the acidosis may contribute to mainta ining the level of intermediates of the tricarboxylic-acid cycle in th is metabolic situation in which the net release of glutamine are produ ced. (C) 1998 Elsevier Science Ltd. All rights reserved.