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.