the market have been increasing since epidemiological and clinical researches have revealed possible effects of PUFA on brain development and curative and/or preventive effects on cardiovascular disease. However, PUFA are very labile and easily oxidizable, thus the maximum beneficial effects of PUFA supplements may not be obtained if they contain significant amounts of toxic OαβUAs, which as commented on above, are being considered as possible causal agents of numerous diseases. Special attention must also be paid to cooking oils used repeatedly in caterings and households, because in those processes very high amounts of OαβUAs are generated and they can be easily absorbed through the diet. Detoxification and related reactions 4-HNE has two reactive groups: the conjugated aldehyde and the C=C double-bond, and the hydroxy group at carbon 4. The α,β-unsaturated ketone serves as a Michael acceptor, adding thiols to give thioether adducts. A small group of enzymes are specifically suited to the detoxification and removal of 4-HNE from cells. Within this group are the glutathione S-transferases (GSTs) such as hGSTA4-4 and hGST5.8, aldose reductase, and aldehyde dehydrogenase. These enzymes have low Km values for HNE catalysis and together are very efficient at controlling the intracellular concentration, up to a critical threshold amount, at which these enzymes are overwhelmed and cell death is inevitable. Glutathione S-transferases hGSTA4-4 and hGST5.8 catalyze the conjugation of glutathione peptides to 4-hydroxynonenal through a conjugate addition to the alpha-beta unsaturated carbonyl, forming a more water-soluble molecule, GS-HNE. While there are other GSTs capable of this conjugation reaction (notably in the alpha class), these other isoforms are much less efficient and their production is not induced by the stress events which cause the formation of 4-HNE (such as exposure to hydrogen peroxide, ultraviolet light, heat shock, cancer drugs, etc.), as the production of the more specific two isoforms is. This result strongly suggests that hGSTA4-4 and hGST5.8 are specifically adapted by human cells for the purpose of detoxifying 4-HNE to abrogate the downstream effects which such a buildup would cause. Increased activity of the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) has been shown to have a protective effect against cardiac ischemia in animal models, and the postulated mechanism given by the investigators was 4-hydroxynonenal metabolism. Export GS-HNE is a potent inhibitor of the activity of glutathione S-transferase, and therefore must be shuttled out of the cell to allow conjugation to occur at a physiological rate. Ral-interacting GTPase