Darmaun D, Welch S, Rini A, Sager B K, Altomare A, Haymond M W
Nemours Children's Clinic, Jacksonville, Florida 32207, USA.
Am J Physiol. 1998 May;274(5):E801-7. doi: 10.1152/ajpendo.1998.274.5.E801.
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 approximately 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 approximately 26% decline in plasma glutamine concentration from 514 +/- 24 to 380 +/- 15 microM (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 mumol.kg-1.h-1; not significant); 3) an approximately 22% rise in leucine oxidation (Ox) from 23 +/- 2 to 28 +/- 2 mumol.kg-1.h-1 (P < 0.01), resulting in an approximately 11% decline in nonoxidative leucine disposal (NOLD = Ra-Ox), an index of protein synthesis, from 100 +/- 6 to 89 +/- 5 mumol.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 decrease estimates of whole body protein synthesis.
本研究旨在确定苯丁酸钠（phi B）是否能在健康人体内急性诱导血浆谷氨酰胺水平降低，若能降低，则是否会降低全身蛋白质合成的评估值。在第一组三名健康受试者中，在研究前24小时给予不同剂量（0、0.18和0.36 g·kg-1·天-1）的phi B：空腹后血浆谷氨酰胺浓度呈剂量依赖性下降，当剂量为0.36 g phi B·kg-1·天-1时下降约25%。第二组六名健康成年人在两个不同的日子里，在空腹状态下接受5小时的L-[1-14C]亮氨酸和L-[1-13C]谷氨酰胺输注：1）在基线条件下；2）在口服phi B（0.36 g·kg-1·天-1）24小时后，顺序随机。24小时的苯丁酸钠治疗导致：1）血浆谷氨酰胺浓度从514±24微摩尔/升降至380±15微摩尔/升，下降约26%（平均值±标准误；配对t检验，P<0.01），谷氨酰胺出现率或从头合成无变化；2）亮氨酸出现率（Ra）无变化，Ra是蛋白质分解的指标（123±7对117±5微摩尔·kg-1·小时-1；无显著性差异）；3）亮氨酸氧化（Ox）从23±2微摩尔·kg-1·小时-1升至28±2微摩尔·kg-1·小时-1，升高约22%（P<0.01），导致非氧化亮氨酸处置（NOLD=Ra-Ox），即蛋白质合成指标，从100±6微摩尔·kg-1·小时-1降至89±5微摩尔·kg-1·小时-1，下降约11%（P<0.05）。数据表明，在健康成年人中，1）大剂量口服苯丁酸钠可作为“谷氨酰胺陷阱”来建立谷氨酰胺耗竭模型；2）血浆谷氨酰胺适度下降不会提高内源性谷氨酰胺的产生率；3）血浆谷氨酰胺短期耗竭会降低全身蛋白质合成的评估值。
