肾功能损害大鼠中 D: -蛋氨酸动力学的改变。

Altered D: -methionine kinetics in rats with renal impairment.

机构信息

Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.

出版信息

Amino Acids. 2011 Apr;40(4):1205-11. doi: 10.1007/s00726-010-0746-5. Epub 2010 Sep 25.

DOI:10.1007/s00726-010-0746-5

PMID:20872028

Abstract

D

-Amino acids are now recognized to be widely present in mammals. In rats, exogenously administered D: -methionine is almost converted into the L: -enantiomer via 2-oxo-4-methylthiobutylic acid as an intermediate. D: -Amino acid oxidase is associated with conversion of D: -methionine into the 2-oxo acid. Since D: -amino acid oxidase is present at the highest activity in the kidney compared to other organ, kidney injury is suggested to cause accumulation of D: -methionine. The purpose of the present study is to assess the role of kidney in the elimination of D: -methionine and metabolic conversion into L: -methionine in rats using a stable isotope methodology. After a bolus i.v. administration of D: -[²H₃)]methionine to 5/6-nephrectomized rats, plasma concentrations of D: -[²H₃]methionine, L: -[²H₃]methionine, and endogenous L: -methionine were determined by a stereoselective GC-MS method. Renal mass reduction slowed down the elimination of D: -[²H₃]methionine. The clearance values of conversion of D: -[²H₃]methionine into the L: -enantiomer in 5/6-nephrectomized rats were one-sixth of those in sham-operated rats. The elimination behavior of D: -[²H₃]methionine observed in rats demonstrated that kidney was the principal organ responsible for chiral inversion of D: -methionine.

摘要

氨基酸现在被广泛认为存在于哺乳动物中。在大鼠中，外源性给予 D：-蛋氨酸几乎通过 2-氧代-4-甲基硫代丁酸作为中间体转化为 L：-对映体。D：-氨基酸氧化酶与 D：-蛋氨酸转化为 2-氧酸有关。由于 D：-氨基酸氧化酶在肾脏中的活性最高，与其他器官相比，肾脏损伤被认为会导致 D：-蛋氨酸的积累。本研究的目的是使用稳定同位素方法评估肾脏在大鼠中消除 D：-蛋氨酸和代谢转化为 L：-蛋氨酸中的作用。在 5/6 肾切除大鼠静脉内推注 D：-[²H₃)]蛋氨酸后，通过立体选择性 GC-MS 方法测定血浆中 D：-[²H₃)]蛋氨酸、L：-[²H₃)]蛋氨酸和内源性 L：-蛋氨酸的浓度。肾质量减少减缓了 D：-[²H₃)]蛋氨酸的消除。5/6 肾切除大鼠中 D：-[²H₃)]蛋氨酸转化为 L：-对映体的清除值是假手术大鼠的六分之一。在大鼠中观察到的 D：-[²H₃)]蛋氨酸的消除行为表明，肾脏是负责 D：-蛋氨酸手性反转的主要器官。