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

F-2-isoprostanes are prostaglandin F-2-like compounds that are formed nonenzymatically by free radical mediated peroxidation of arachidonic acid. Intermediate in the pathway of the formation of isoprostanes are labile prostaglandin H-2-like bicyclic endoperoxides (H-2-isoprostanes), which are reduced to F-2-isoprostanes and also undergo rearrangement in vivo to form E-ring and D-ring isoprostanes, isothromboxanes, and highly reactive acyclic gamma-ketoaldehdyes (isoketals). Docosahexaenoic acid (C22:6omega3) is highly enriched in neurons in the brain and is highly susceptible to oxidation. Free radical mediated oxidation of docosa-hexaenoic acid results in the formation of isoprostane-like compounds (neuroprostanes). F-4- and E-4/D-4-neuroprostanes as well as neuroketals have been shown to be produced in vivo. Finally, we recently discovered a new pathway of lipid peroxidation that forms compounds with a substituted tetrahydrofuran ring (isofurans). Oxygen concentrations differentially modulate the formation of isoprostanes and isofurans; at elevated oxygen concentrations, the formation of isofurans is favored whereas the formation of isoprostanes is disfavored. (C) 2003 Elsevier Ireland Ltd. All rights reserved.