Hepatic aldehyde dehydrogenases and lipid peroxidation

Abstract

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 (K m of approximately 16 μM) 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 K m values in the millimolar range. Addition of the cytosolic fraction of rat liver produced a significant decrease in the accumulation of MDA during CCl 4-induced microsomal membrane lipid peroxidation but did not protect cytochrome P-450 from destruction. The mitochandrial low K m 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.