Hjelle J J, Petersen D R
Pharmacol Biochem Behav. 1983;18 Suppl 1:155-60. doi: 10.1016/0091-3057(83)90164-8.
Recent findings have shown that microsomal membrane lipid peroxidation generates a variety of reactive aldehydic products. The interaction of lipid peroxidation products with hepatic aldehyde dehydrogenases (ALDH) was studied using rat liver subcellular fractions. The well-documented membrane peroxidation product malondialdehyde (MDA) was studied to determine if ALDH isozymes play a role in metabolism of this aldehyde. The cytosolic and mitochondrial hepatic subcellular fractions were found to contain ALDH isozymes capable of oxidizing MDA. The kinetic properties of a cytosolic ALDH (Km of approximately 16 microM) suggest that this enzyme may be involved in the metabolism of MDA in vivo. Both the cytosolic and mitochondrial fractions also contained an ALDH isozyme with Km values in the millimolar range. Addition of the cytosolic fraction of rat liver produced a significant decrease in the accumulation of MDA during CCl4-induced microsomal membrane lipid peroxidation but did not protect cytochrome P-450 from destruction. The mitochondrial low Km ALDH isozyme was found to be a target enzyme for inhibition during in vitro microsomal lipid peroxidation. These studies show that a select ALDH isozyme is sensitive to inhibition during membrane lipid peroxidation whereas other isozymes may be involved in the metabolism of aldehydic peroxidation products.
最近的研究结果表明，微粒体膜脂质过氧化会产生多种活性醛类产物。利用大鼠肝脏亚细胞组分研究了脂质过氧化产物与肝脏醛脱氢酶（ALDH）的相互作用。对有充分文献记载的膜过氧化产物丙二醛（MDA）进行了研究，以确定ALDH同工酶是否在这种醛的代谢中发挥作用。发现胞质和线粒体肝脏亚细胞组分含有能够氧化MDA的ALDH同工酶。一种胞质ALDH的动力学特性（Km约为16 microM）表明，这种酶可能参与体内MDA的代谢。胞质和线粒体组分还都含有Km值在毫摩尔范围内的一种ALDH同工酶。加入大鼠肝脏的胞质组分可使四氯化碳诱导的微粒体膜脂质过氧化过程中MDA的积累显著减少，但不能保护细胞色素P - 450免受破坏。发现线粒体低Km的ALDH同工酶是体外微粒体脂质过氧化过程中的抑制靶酶。这些研究表明，一种特定的ALDH同工酶在膜脂质过氧化过程中对抑制敏感，而其他同工酶可能参与醛类过氧化产物的代谢。
