US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Am J Clin Nutr. 2011 Jun;93(6):1248-54. doi: 10.3945/ajcn.110.009043. Epub 2011 Apr 13.
Phenylbutyrate is a drug used in patients with urea cycle disorder to elicit alternative pathways for nitrogen disposal. However, phenylbutyrate administration decreases plasma branched-chain amino acid (BCAA) concentrations, and previous research suggests that phenylbutyrate administration may increase leucine oxidation, which would indicate increased protein degradation and net protein loss.
We investigated the effects of phenylbutyrate administration on whole-body protein metabolism, glutamine, leucine, and urea kinetics in healthy and ornithine transcarbamylase-deficient (OTCD) subjects and the possible benefits of BCAA supplementation during phenylbutyrate therapy.
Seven healthy control and 7 partial-OTCD subjects received either phenylbutyrate or no treatment in a crossover design. In addition, the partial-OTCD and 3 null-OTCD subjects received phenylbutyrate and phenylbutyrate plus BCAA supplementation. A multitracer protocol was used to determine the whole-body fluxes of urea and amino acids of interest.
Phenylbutyrate administration reduced ureagenesis by ≈15% without affecting the fluxes of leucine, tyrosine, phenylalanine, or glutamine and the oxidation of leucine or phenylalanine. The transfer of (15)N from glutamine to urea was reduced by 35%. However, a reduction in plasma concentrations of BCAAs due to phenylbutyrate treatment was observed. BCAA supplementation did not alter the respective baseline fluxes.
Prolonged phenylbutyrate administration reduced ureagenesis and the transfer of (15)N from glutamine to urea without parallel reductions in glutamine flux and concentration. There were no changes in total-body protein breakdown and amino acid catabolism, which suggests that phenylbutyrate can be used to dispose of nitrogen effectively without adverse effects on body protein economy.
苯丁酸钠是一种用于尿素循环障碍患者的药物，可诱导氮排泄的替代途径。然而，苯丁酸钠的给药会降低血浆支链氨基酸（BCAA）的浓度，先前的研究表明，苯丁酸钠的给药可能会增加亮氨酸的氧化，这表明蛋白质降解和净蛋白丢失增加。
我们研究了苯丁酸钠给药对健康和鸟氨酸转氨甲酰酶缺陷（OTCD）受试者全身蛋白质代谢、谷氨酰胺、亮氨酸和尿素动力学的影响，以及在苯丁酸钠治疗期间补充 BCAA 的可能益处。
7 名健康对照和 7 名部分 OTCD 受试者以交叉设计接受苯丁酸钠或无治疗。此外，部分 OTCD 和 3 名完全 OTCD 受试者接受苯丁酸钠和苯丁酸钠加 BCAA 补充。使用多示踪剂方案来确定尿素和感兴趣的氨基酸的全身通量。
苯丁酸钠给药使尿素生成减少约 15%，而不影响亮氨酸、酪氨酸、苯丙氨酸或谷氨酰胺的通量以及亮氨酸或苯丙氨酸的氧化。来自谷氨酰胺的（15）N 向尿素的转移减少了 35%。然而，由于苯丁酸钠治疗，观察到血浆 BCAA 浓度降低。BCAA 补充并没有改变各自的基线通量。
长期苯丁酸钠给药可减少尿素生成和（15）N 从谷氨酰胺向尿素的转移，而谷氨酰胺通量和浓度没有平行减少。全身蛋白质分解和氨基酸分解代谢没有变化，这表明苯丁酸钠可有效地处理氮，而不会对身体蛋白质代谢产生不利影响。
