Acute metabolic acidosis decreases muscle protein synthesis but not albumin synthesis in humans

Chronic metabolic acidosis induces negative nitrogen balance by either incr eased protein breakdown or decreased protein synthesis. Few data exist rega rding effects of acute metabolic acidosis on protein synthesis. We investig ated fractional synthesis rates (FSRs) of muscle protein and albumin, plasm a concentrations of insulin-like growth factor-I (IGF-I), thyroid-stimulati ng hormone (TSH), and thyroid hormones (free thyroxin [fT(4)] and triiodoth yronine [fT(3)]) in seven healthy human volunteers after a stable controlle d metabolic period of 5 days and again 48 hours later after inducing metabo lic acidosis by oral ammonium chloride intake (4.2 mmol/kg/d divided in six daily doses). Muscle and albumin FSRs were obtained by the [(2)H(5)ring]ph enylalanine flooding technique. Ammonium chloride induced a significant dec rease in pH (7.43 +/- 0.02 versus 7.32 +/- 0.04; P < 0.0001) and bicarbonat e concentration (24.6 +/- 1.6 versus 16.0 +/- 2.7 mmol/L; P < 0.0001) withi n 48 hours. Nitrogen balance decreased significantly on the second day of a cidosis. The FSR of muscle protein decreased (1.94 +/- 0.25 versus 1.30 +/- 0.39; P < 0.02), whereas the FSR of albumin remained constant. TSH levels increased significantly (1.1 +/- 0.5 versus 1.9 +/- 1.1 mU/L; P = 0.03), wh ereas IGF-I, fT(4), and fT(3) levels showed no significant change. We concl ude that acute metabolic acidosis for 48 hours in humans induces a decrease in muscle protein synthesis, which contributes substantially to a negative nitrogen balance. In contrast to prolonged metabolic acidosis of 7 days, a short period of acidosis in the present study did not downregulate, albumi n synthesis. (C) 2001 by the National Kidney Foundation, Inc.