Mitchell D Y, Petersen D R
Toxicol Appl Pharmacol. 1987 Mar 15;87(3):403-10. doi: 10.1016/0041-008x(87)90245-6.
Lipid peroxidation of microsomal membranes produces a large number of aldehydes, alcohols, and ketones, of which some are cytotoxic. trans-4-Hydroxy-2-nonenal (4HN) and trans-2-hexenal (HX) are two alpha-beta unsaturated aldehydes which are major and minor lipid peroxidation products, respectively. The role of aldehyde dehydrogenase (ALDH) in the oxidation of 4HN and HX was examined using semipurified mitochondrial, cytosolic, and microsomal ALDH isozymes prepared from male Sprague-Dawley rat liver. High- and low- affinity mitochondrial and high-affinity cytosolic ALDH isozymes were able to oxidize 4HN. The affinities of the three isozymes for 4HN, reported as the V/K values, are 0.258, 0.032 and 0.030 nmol NADH formed/min/mg protein/mumol 4HN/liter, respectively. The low-affinity cytosolic and microsomal forms of ALDH are unable to oxidize 4HN. The high-affinity mitochondrial, low-affinity cytosolic, and microsomal ALDH isozymes oxidized HX, displaying V/K values of 0.600, 0.058, and 0.058 nmol NADH formed/min/mg protein/mumol HX/liter, respectively. Oxidation of HX by the low-affinity mitochondrial and high-affinity cytosolic isozyme was not detected. This study indicates that ALDH may participate in the in vivo metabolism of cytotoxic aldehydic products formed during lipid peroxidation.
微粒体膜的脂质过氧化作用会产生大量醛类、醇类和酮类物质，其中一些具有细胞毒性。反式-4-羟基-2-壬烯醛（4HN）和反式-2-己烯醛（HX）是两种α-β不饱和醛，分别是脂质过氧化的主要和次要产物。使用从雄性Sprague-Dawley大鼠肝脏制备的半纯化线粒体、胞质和微粒体醛脱氢酶（ALDH）同工酶，研究了ALDH在4HN和HX氧化中的作用。高亲和力和低亲和力的线粒体ALDH同工酶以及高亲和力的胞质ALDH同工酶能够氧化4HN。这三种同工酶对4HN的亲和力（以V/K值表示）分别为0.258、0.032和0.030 nmol NADH生成量/分钟/毫克蛋白质/微摩尔4HN/升。低亲和力的胞质和微粒体形式的ALDH无法氧化4HN。高亲和力的线粒体、低亲和力的胞质和微粒体ALDH同工酶能够氧化HX，其V/K值分别为0.600、0.058和0.058 nmol NADH生成量/分钟/毫克蛋白质/微摩尔HX/升。未检测到低亲和力的线粒体和高亲和力的胞质同工酶对HX的氧化作用。这项研究表明，ALDH可能参与脂质过氧化过程中形成的具有细胞毒性的醛类产物的体内代谢。
