Steady-state and non-steady-state measurements of plasma glutamine turnover in humans

To compare steady-state glutamine turnover using nitrogen, carbon, and hydrogen tracers and to test the validity of monocompartmental equations to determine plasma glutamine turnover under non-steady-state conditions, we infused 10 normal postabsorptive volunteers simultaneously with [3,4-3H]glutamine, [2-15N]glutamine, and [U-14C]glutamine for 4 h to isotopic steady state. Eight of the ten subjects were subsequently infused in a stepwise fashion with exogenous glutamine. Plasma glutamine enrichment and specific activities fit a monoexponential model well (r = 0.89, 0.92, and 0.92 for [2-15N]-, [U-14C]-, and [3,4-3H]glutamine, respectively). Volumes of distribution for each tracer (362 +/- 58, 433 +/- 51, and 446 +/- 63 ml/kg) and the transfer rate constants (0.0224 +/- 0.0020, 0.0222 +/- 0.0020, and 0.0240 +/- 0.0023 min(-1)) for [2-15N]-, [U-14C]-, and [3,4-3H]glutamine, respectively, were not significantly different from one another. However, turnover of glutamine determined with [3,4-3H]glutamine (6.14 +/- 0.54 micromol x kg(-1) x min(-1)) exceeded that determined with [U-14C]glutamine (5.72 +/- 0.541 micromol x kg(-1) x min(-1); P < 0.03), which in turn exceeded that determined with [2-15N]glutamine (4.67 +/- 0.39 micromol x kg(-1) x min(-1), P < 0.01). The monocompartmental non-steady-state equations of both DeBodo et al. (DeBodo, R., R. Steele, A. Dunn, and J. Bishop. Rec. Prog. Horm. Res. 19: 445-448, 1963) and Finegood et al. (Finegood, D., R. Bergman, and M. Vranic. Diabetes 36: 914-924, 1987) yielded acceptable approximations of predicted rates of glutamine plasma appearance with deviations from predicted rates from 0.2 to 1.6% (Finegood et al.) and from 0.1 to 8.2% (DeBodo et al.). Use of a 0.75 pool fraction most closely approximated predicted rates.