D. Darmaun et al., PHENYLBUTYRATE-INDUCED GLUTAMINE DEPLETION IN HUMANS - EFFECT ON LEUCINE METABOLISM, American journal of physiology: endocrinology and metabolism, 37(5), 1998, pp. 801-807
The present study was designed to determine whether sodium phenylbutyr
ate (Phi B) acutely induces a decrease in plasma glutamine in healthy
humans, and, if so, will decrease estimates of whole body protein synt
hesis. 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 bef
ore study: postabsorptive plasma glutamine concentration declined in a
dose-dependent manner, achieving an approximate to 25% decline for a
dose of 0.36 g Phi B.kg(-1).day(-1). A second group of six healthy adu
lts received 5-h infusions of L-[1-C-14]leucine and L-[1-C-13]glutamin
e 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 w
as associated with 1) an approximate to 26% decline in plasma glutamin
e concentration from 514 +/- 24 to 380 +/- 15 mu M (means +/- SE; P <
0.01 with paired t-test) with no change in glutamine appearance rate o
r de novo synthesis; 2) no change in leucine appearance rate (R-a), an
index of protein breakdown (123 +/- 7 vs. 117 +/- 5 mu mol.kg(-1).h(-
1); not significant); 3) an approximate to 22% rise in leucine oxidati
on (Ox) from 23 +/- 2 to 28 +/- 2 mu mol.kg(-1).h(-1) (P < 0.01), resu
lting in an approximate to 11% decline in nonoxidative leucine disposa
l (NOLD = R-a - Ox), an index of protein synthesis, from 100 +/- 6 to
89 +/- 5 mu mol.kg(-1).h(-1) (P < 0.05). The data suggest that, in hea
lthy adults, 1) large doses of oral phenylbutyrate can be used as a ''
glutamine trap'' to create a model of glutamine depletion; 2) a modera
te decline in plasma glutamine does not enhance rates of endogenous gl
utamine production; and 3) a shortterm depletion of plasma glutamine d
ecreases estimates of whole body protein synthesis.