Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats.
To investigate branched-chain, amino acid metabolism (BCAA) in muscle in chronic renal failure (CRF), we studied rats with moderately severe uremia (PUN 110 approximately mg/dl) and spontaneous metabolic acidosis (bicarbonate, 19 +/- 1 mEq/liter). Plasma BCAA levels in CRF compared to pair-fed control rats were approximately 15% lower and muscle valine was 93 microM lower (P less than 0.05). BCAA metabolism was measured in incubated epitrochlearis muscles using L-[1-14C]valine or L-[1-14C]leucine in the presence and absence of insulin. BCAA decarboxylation was increased (P less than 0.05) and insulin-stimulated BCAA incorporation into protein was blunted (P less than 0.05) by CRF. Since we have found that metabolic acidosis, by itself, stimulates muscle branched-chain, ketoacid dehydrogenase activity, another group of CRF and control rats was given NaHCO3 which corrected the acidosis, but not the azotemia. BCAA decarboxylation in muscle was reduced in CRF rats given NaHCO3, and this was reflected in increased plasma and muscle BCAA concentrations. We conclude that in CRF, chronic metabolic acidosis stimulates BCAA decarboxylation in skeletal muscle and this could contribute to the reduced intra- and extracellular concentrations of BCAA. Correction of acidosis should be a goal of therapy in CRF, especially when dietary regimens restrict intake of BCAA.
Hara
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Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
May
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RC
Kelly
R A
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Mitch
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WE
D000138:Acidosis / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D004044:Dietary Proteins / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000378:metabolism*; D014633:Valine / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins; D007930:Leucine; D014633:Valine