Lysine α-ketoglutarate reductase, but not saccharopine dehydrogenase, is subject to substrate inhibition in pig liver
Lysine α-ketoglutarate reductase, but not saccharopine dehydrogenase, is subject to substrate inhibition in pig liver
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DOI：
10.1016/j.nutres.2011.06.001
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发表时间：
2011-07-01
影响因子：
4.5
通讯作者：
Ball, Ronald O.
中科院分区：
文献类型：
--
作者：
Pink, Desmond B. S.;Gatrell, Stephanie K.;Ball, Ronald O.
赖氨酸α-酮戊二酸还原酶（LKR）是赖氨酸催化酶主要途径中的起始酶，其活性是全身赖氨酸状态的主要决定因素。过去的研究表明，LKR活动主要是肝脏;最近，在体内数据表明，其他组织也可以分解代谢赖氨酸。本研究的假设是赖氨酸催化酶在猪的肝外组织中发生，并且所涉及的酶可能受到抑制或激活。利用来自商品猪不同组织的线粒体，测定了LKR和糖精脱氢酶的活性。肝线粒体LKR活性最高，酶受底物抑制。来自肌肉、肾脏、心脏和肠上皮细胞的线粒体都具有可测量的LKR活性。LKR活性被多种化合物显著抑制，包括糖精、α-氨基己二酸、α-酮己二酸、5-羟基-L-赖氨酸和几种金属。在从肝脏、肌肉和肠上皮细胞分离的线粒体中证实了（14）C-赖氨酸氧化为（14）CO（2）。蛋白质印迹法证实存在的α-氨基己二酸δ-半醛合酶蛋白在一些肝外组织。这些数据表明，在这些肝外组织中，最显著的是在肠和肌肉细胞中，赖氨酸降解的能力显著。这些组织应该被认为是全身赖氨酸催化剂的重要贡献者。(C)2011 Elsevier Inc. All rights reserved.
The activity of lysine a-ketoglutarate reductase (LKR), the initial enzyme in the principal pathway of lysine catabolism, is a primary determinant of whole-body lysine status. Past research indicated that LKR activity was predominantly hepatic; recent, in vivo data suggest that other tissues can also catabolize lysine. The hypothesis of this investigation was that lysine catabolism takes place in extrahepatic tissues in pigs and that the enzymes involved may be subject to inhibition or activation. Using mitochondria from various tissues of market-age pigs, the activities of LKR and saccharopine dehydrogenase were measured. Liver mitochondria had the highest LKR activity, and the enzyme was subject to substrate inhibition. Mitochondria from the muscle, kidney, heart, and intestinal epithelial cells all had measurable LKR activity. The LKR activity was significantly inhibited by a variety of compounds including saccharopine, alpha-aminoadipate, alpha-ketoadipate, 5-hydroxy-L-lysine, and several metals. Oxidation of (14)C-lysine to (14)CO(2) was demonstrated in mitochondria isolated from the liver, muscle, and intestinal epithelial cells. Western blotting confirmed the presence of the alpha-aminoadipate delta-semialdehyde synthase protein in some extrahepatic tissues. These data show a significant capacity for lysine degradation in these extrahepatic tissues, most notably in cells of the intestine and muscle. These tissues should be considered important contributors to whole-body lysine catabolism. (C) 2011 Elsevier Inc. All rights reserved.