Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate, Pyruvate, and 3‐Hydroxybutyrate Transport Across the Blood‐Brain Barrier
Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate, Pyruvate, and 3‐Hydroxybutyrate Transport Across the Blood‐Brain Barrier
复制标题
枫糖浆尿病中积累的 2-含氧酸抑制乳酸、丙酮酸和 3-羟基丁酸跨血脑屏障的转运
DOI：
--
复制
发表时间：
1982
影响因子：
4.7
通讯作者：
V. Cunningham
中科院分区：
文献类型：
--
作者：
J. E. Cremer;H. M. Teal;V. Cunningham
摘要：数据支持(-)-d-3-羟基丁酸酯通过血脑屏障(BBB)的转运是载体介导的过程。21日龄戊巴比妥钠麻醉大鼠的动力学参数为Vmax 2.0μmol.g−1.min−1，Km 29 mm，Kd 0.024 mL.g−1.min−1，与同龄动物的乳酸和丙酮酸转运的Vmax相同。这三种底物的转运都对低浓度的2-氧代-3-甲基丁酸或2-0x0-4-甲基戊酸的抑制很敏感，这两种2-氧基酸可以在枫糖尿病患者体内积聚。2-氧代酸的Km值比相应的Km值低几倍。2-氧代-3-苯丙酸酯是一种较差的缓蚀剂。各种单羧酸对血脑屏障运输系统的相对亲和力使其有别于脑、心脏和肝脏线粒体、人红细胞和艾氏腹水-肿瘤细胞中描述的类似系统。
Abstract: Data are presented in support of the transport of (‐)‐d‐3‐hydroxybutyrate across the blood‐brain barrier (BBB) being a carrier‐mediated process. The kinetic parameters in 21‐day‐old pentobarbital‐anaesthetized rats were Vmax 2.0 μmol.g−1.min−1, Km 29 mM, and KD 0.024 ml.g−1.min−1. The value for Vmax was the same as that for l‐lactate and pyruvate transport in animals of the same age. The transport of all three substrates was sensitive to inhibition by low concentrations of either 2‐oxo‐3‐methylbutanoate or 2‐0x0‐4‐methylpentanoate, the 2‐oxo acids that can accumulate in patients with maple‐syrup‐urine disease. The Km values for the 2‐oxo acids were severalfold lower than the respective Km values. 2‐oxo‐3‐phenylpropionate was a poor inhibitor. The relative affinities of the various monocarboxylic acids for the transport system of the BBB distinguished it from similar systems described in brain, heart, and liver mitochondria; human erythrocytes; and Ehrlich ascites‐tumour cells.