A review of recent studies on the metabolism of exogenous and endogenous malondialdehyde.

1. The generation of malondialdehyde (MDA), a mutagenic product of the oxidative decomposition of highly unsaturated fatty acids in vivo, is increased by exposure to certain environmental oxidants and xenobiotics. 2. This increase is reflected in enhanced excretion of several MDA derivatives in the urine. The main urinary metabolites of MDA have been identified as N-epsilon-(2-propenal)lysine and its N-alpha-acetyl ester. 3. Two minor metabolites have been identified as enaminals formed by reactions with the phospholipid bases serine and ethanolamine. A further MDA metabolite has been identified as a cyclized adduct with guanine. 4. These urinary compounds reflect the turnover of proteins, phospholipids and nucleic acids that have been modified by reactions with MDA in vivo. Monitoring of the urinary adduct with guanine may provide a practicable method of assessing the effect of xenobiotics and other factors on in vivo lipid peroxidation. 5. The proportion of total MDA in the diet, blood, urine and solid tissues that exists in the free state appears to be negligible. 6. Chronic oral administration of the enol Na salt of MDA to animals produced no significant pathology except for dose-dependent lesions of hepatic nuclei. Nuclear abnormalities in cultured rat skin fibroblasts were seen at intracellular concentrations as low as 10(-7) M.