The biochemistry of the isoprostane, neuroprostane, and isofuran Pathways of lipid peroxidation

Abstract

Isoprostanes are prostaglandin-like compounds that are formed non-enzymatically by free radical-catalyzed peroxidation of arachidonic acid (C20:4omega6). Intermediates in the pathway of the formation of isoprostanes are labile prostaglandin H2-like bicyclic endoperoxides (H2-isoprostanes). H2-isoprostanes are reduced to form F-ring isoprostanes (F2-isoprostanes), but they also undergo chemical rearrangement in vivo to form E2- and D2-isoprostanes, isothromboxanes, and highly reactive acyclic y-ketoaldehdyes (isoketals). E2- and D2-isoprostanes also undergo dehydration in vivo to form cyclopentenone A2- and J2-isoprostanes. Docosahexaenoic acid (C22:6omega3) is highly enriched in neurons in the brain and is highly susceptible to oxidation. Free radical-catalyzed oxidation of docosahexaenoic acid results in the formation of isoprostane-like compounds (neuroprostanes). F4-, D4-, E4-, A4-, and J4-neuroprostanes and neuroketals have all been shown to be produced in vivo. In addition, we recently discovered a new pathway of lipid peroxidation that forms compounds with a substituted tetrahydrofuran ring (isofurans). Oxygen concentration differentially modulates the formation of isoprostanes and isofurans. As oxygen concentrations increase, the formation of isofurans is favored whereas the formation of isoprostanes becomes disfavored.