CATABOLISM OF BRANCHED-CHAIN AMINO-ACIDS BY DIAPHRAGM MUSCLES OF FASTED AND DIABETIC RATS
CATABOLISM OF BRANCHED-CHAIN AMINO-ACIDS BY DIAPHRAGM MUSCLES OF FASTED AND DIABETIC RATS
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DOI：
10.1016/0026-0495(85)90018-6
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发表时间：
1985-01-01
影响因子：
9.8
通讯作者：
BUSE, MG
中科院分区：
文献类型：
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作者：
AFTRING, RP;MANOS, PN;BUSE, MG
在正常大鼠、链脲佐菌素糖尿病大鼠和隔夜禁食大鼠的横隔肌上，研究了支链氨基酸亮氨酸和缬氨酸的体外分解代谢。当横隔膜与葡萄糖孵育时，糖尿病或禁食对[1-14C]支链氨基酸的氧化和转氨化都有类似程度的刺激。与丙酮酸孵育时，横隔膜的亮氨酸和缬氨酸转氨率增加；糖尿病大鼠横隔膜的转氨率最高。空腹或糖尿病大鼠膈肌中亮氨酸和缬氨酸的氧化被丙酮酸抑制，而对其无影响或略有刺激。糖尿病大鼠的横隔膜在与丙酮酸孵育时，氧化的支链氨基酸是对照组的2-3倍。在丙酮酸存在或不存在的情况下，与[14C]亮氨酸孵育的横隔膜产生的细胞外α-酮基异己酸酯(KIC；亮氨酸转氨化产物)的比放射性对于所有组(喂食组、禁食组或糖尿病组)都是相似的。空腹或糖尿病大鼠经葡萄糖孵育后，隔膜对[1-14C]KIC的氧化作用与对照大鼠的相同或更小。与丙酮酸孵育对对照横隔膜KIC氧化的抑制作用明显大于糖尿病或禁食大鼠的横隔膜。显然，通过支链氨基酸转氨酶的流量受到正常和隔夜禁食大鼠膈肌氨基受体可获得性的限制，糖尿病大鼠膈肌氨基受体的可获得性在更大程度上是有限的。在空腹和糖尿病中，通过转氨酶的流量可能是横隔膜加速支链氨基酸氧化的主要决定因素。在禁食和糖尿病大鼠的横隔膜中，通过支链α-酮酸脱氢酶复合体的流量明显抵抗丙酮酸的抑制，而丙酮酸通常在对照组中观察到。
In vitro catabolism of branched-chain amino acids, leucine and valine, was investigated using diaphragm muscles from normal, streptozotocin-diabetic and overnight fasted rats. Oxidation and transamination of [1-14C]branched-chain amino acids were both stimulated to a similar extent by diabetes or fasting, when diaphragms were incubated with glucose. Transamination of leucine and valine was increased when diaphragms were incubated with pyruvate; stimulation of transamination was greatest in diaphragms from diabetic rats. Leucine and valine oxidation by control diaphragms was inhibited by pyruvate while it was unchanged or slightly stimulated in diaphragms from fasted or diabetic rats. Diaphragms from diabetic rats oxidized 2- to 3-fold more branched-chain amino acids than controls when they were incubated with pyruvate. The specific radioactivity of extracellular .alpha.-ketoisocaproate (KIC; the product of leucine transamination) produced by diaphragms incubated with [14C]leucine was similar for all groups (fed, fasted, or diabetic) in the presence or absence of pyruvate. Oxidation of [1-14C]KIC by diaphragms from fasted or diabetic rats, incubated with glucose, was the same or less than KIC oxidation by control diaphragms. Incubation with pyruvate inhibited KIC oxidation by control diaphragms to a significantly greater degree than that by diaphragms from diabetic or fasted rats. Apparently, flux through branched-chain amino acid transaminase is limited by the availability of amino group acceptors in diaphragms from normal and overnight fasted rats, and to a greater extent in diaphragms from diabetic rats. Flux through the transaminase may be a major determinant of accelerated branched-chain amino acid oxidation by diaphragms in fasting and diabetes. In diaphragms of fasted and diabetic rats, flux through the branched-chain .alpha.-ketoacid dehydrogenase complex apparently is resistant to inhibition by pyruvate, which is normally observed in controls.