Metabolism of the lipid peroxidation product 4-hydroxynonenal by isolated hepatocytes and by liver cytosolic fractions

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Abstract
The metabolism of the lipid peroxidation product 4-hydroxynonenal and of several other related aldehydes by isolated hepatocytes and rat liver subcellular fractions was investigated. Hepatocytes rapidly metabolize 4-hydroxynonenal in an O2-independent process with a maximum rate (depending on cell preparation) ranging from 130-230 nmol/min per 106 cells (average 193 .+-. 50). The aldehyde is also rapidly utilized by whole rat liver homogenate and the cytosolic fraction (140,000 g supernatant) supplemented with NADH, whereas purified nuclei, mitochondria and microsomes supplemented with NADH show no noteworthy consumption of the aldehyde. In cytosol, the NADH-mediated metabolism of the aldehyde exhibits a 1:1 stoichiometry, i.e., 1 mol of NADH oxidized/mol of hydroxynonenal consumed, and the apparent Km value for the aldehyde is 0.1 mM. Addition of pyrazole (10 mM) or heat inactivation of the cytosol completely abolishes aldehyde metabolism. The various findings strongly suggest that hepatocytes and rat liver cytosol, respectively, convert 4-hydroxynonenal enzymically to the corresponding alcohol, non-2-ene-1,4-diol.

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