Differential effects of amino acid and ketoacid on protein metabolism in humans

We examined the effects of insulin, amino acid (AA), and branched-chain ketoacid (KA) availability on leucine kinetics in eight healthy volunteers (age = 22 ± 2 y, body mass index = 24 ± 1 kg) by using the euglycemic insulin clamp and [1-¹⁴C] leucine turnover techniques. Four experimental conditions were studied: study I, hyperinsulinemia; study II, hyperinsulinemia with maintenance of basal plasma AA and branched-chain KA concentrations; study III, hyperinsulinemia with hyperaminoacidemia and basal plasma branched-chain KA concentrations; and study IV, hyperinsulinemia plus basal plasma AA concentrations and elevated branched-chain KA levels. Basal endogenous leucine flux (ELF) averaged 1.20 ± 0.05 (μmol · kg^-1 · min^-1, mean ± SE); basal leucine oxidation (LOX) was 0.25 ± 0.01; and basal non-oxidative leucine disposal (NOLD) was 0.95 ± 0.04. ELF significantly decreased in study I (0.77 ± 0.06 μmol · kg^-1 · min^-1, P < 0.01 versus basal). When plasma AA and branched-chain KA were either maintained at their basal levels (study II) or increased above baseline values (studies III and IV), ELF declined further (0.64 ± 0.05, 0.66 ± 0.02, and 0.66 ± 0.03 μmol · kg^-1 · min^-1, respectively; all Ps < 0.01 versus basal and P < 0.01 versus study I). LOX declined in study I (0.12 ± 0.02 μmol · kg^-1 · min^-1, P < 0.01 versus basal) but increased significantly in studies II, III, and IV (0.31 ± 0.04, 0.37 ± 0.03, and 0.40 ± 0.03 μmol · kg^-1 · min^-1, respectively, all Ps < 0.01 versus basal, P < 0.05 study IV versus study II, and P < 0.05 study III versus study II). NOLD declined in study I (0.65 ± 0.05 μmol/kg · min, P < 0.01 versus basal), whereas neither the maintenance of basal plasma AA/branched-chain KA levels (study II; 0.89 ± 0.2 μmol · kg^-1 · min^-1) nor the elevation of plasma branched-chain KA concentration (study IV; 0.96 ± 0.1 μmol · kg^-1 · min^-1) increased NOLD above baseline level. A stimulation of NOLD was observed only when plasma AA levels were increased (study III; 1.23 ± 0.03 μmol/kg · min, P < 0.01 versus basal). In conclusion, the present data do not support the concept of a direct anabolic action of ketoanalogs but do provide additional evidence for the pivotal role of AA availability in the stimulation of whole-bodyprotein synthesis. Copyright (C) 2000 Elsevier Science Inc.