Mechanism of inhibition of rat liver class 2 ALDH by 4-hydroxynonenal.

Abstract

Lipid oxidation is a pathological process that results in the peroxidation of cellular membrane lipids ultimately giving rise to a number of reactive, cytotoxic, aldehydic products (Esterbauer et al, 1991). 4-hydroxy-2-trans-nonenal (4-HNE) malondialdehyde (MDA), the most abundant aldehydes produced during lipid peroxidation, have a relatively long half-life and are capable of diffusing to distant sites within the cell of origin or into adjacent cells. 4-HNE can produce a variety of adverse cellular effects which have b summarized in detail elsewhere (Schauer et al, 1990) and include the inhibition of various enzymes (Vander Jagt et al, 1997). The ability of certain biogenic aldehydes to produce diverse biological and cytotoxic effects can be attributed to their α, β-unsaturated configuration that gives the compounds strong electrophilic properties (Esterbauer et al, 1991).us, investigators attribute these adverse effects to the formation of aldehyde ad- ducts h cellular protein nucleophiles through covalent alkylation of sulfhydryl, primary amino, and histidyl groups of proteins (Hartley et al, 1997; Uchida and Stadtman, 1993).