Amplification of Tissue Peroxides in Disease

Abstract

The fatty acid oxygenases, cyclooxygenase and lipoxygenase, require hydroperoxides to achieve maximal rates of reaction, and their reaction products are hydroperoxides that can stimulate a faster oxygenation reaction. The cyclooxygenase can be stimulated to half-maximal velocity by 20 picomoles of lipid hydroperoxide per ml (1), while it can generate nanomoles of the hydroperoxide, prostaglandin G₂ (PGG₂). Soybean lipoxygenase, and all other lipoxygenases, also react faster as the level of lipid hydroperoxide is amplified. Thus, intracellular amplification of lipid hydroperoxides by the fatty acid oxygenases may be closely related to high rates of formation of eicosanoids (prostaglandins and leukotrienes). This relationship has broader importance when overproduction of eicosanoids is recognized to be a common occurrence in many major pathophysiological events (2). The intracellular amplification by the fatty acid oxygenases of “triggering” levels of hydroperoxide (3) to higher levels that permit pathological rates of eicosanoid synthesis needs careful study. Intracellular levels of to 10⁻⁹to 10⁻⁷ M lipid hydroperoxide seem likely to be involved in this amplification.