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Am J Physiol Endocrinol Metab 274: E801-E807, 1998;
0193-1849/98 $5.00
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Vol. 274, Issue 5, E801-E807, May 1998

Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism

Dominique Darmaun, Susan Welch, Annie Rini, Brenda K. Sager, Astride Altomare, and Morey W. Haymond

Nemours Children's Clinic, Jacksonville, Florida 32207; Centre de Recherche en Nutrition Humaine, 44093 Nantes Cedex 1, France; and United States Department of Agriculture Children's Nutrition Research Center, Houston, Texas 77030-2600

The present study was designed to determine whether sodium phenylbutyrate (Phi B) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g · kg-1 · day-1) of Phi B were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an approx 25% decline for a dose of 0.36 g Phi B · kg-1 · day-1. A second group of six healthy adults received 5-h infusions of L-[1-14C]leucine and L-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with Phi B (0.36 g · kg-1 · day-1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an approx 26% decline in plasma glutamine concentration from 514 ± 24 to 380 ± 15 µM (means ± SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 ± 7 vs. 117 ± 5 µmol · kg-1 · h-1; not significant); 3) an approx 22% rise in leucine oxidation (Ox) from 23 ± 2 to 28 ± 2 µmol · kg-1 · h-1 (P < 0.01), resulting in an approx 11% decline in nonoxidative leucine disposal (NOLD = Ra - Ox), an index of protein synthesis, from 100 ± 6 to 89 ± 5 µmol · kg-1 · h-1 (P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decreases estimates of whole body protein synthesis.

protein metabolism; nutrition; stable isotopes; radioactive tracers


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