The biochemistry of the isoprostane, neuroprostane, and isofuran pathways of lipid peroxidation.
F2-isoprostanes are prostaglandin F2-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 H2-like bicyclic endoperoxides (H2-isoprostanes), which are reduced to F2-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 docosahexaenoic acid results in the formation of isoprostane-like compounds (neuroprostanes). F4- and E4/D4-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.
Roberts
L Jackson
LJ
Departments of Pharmacology and Medicine, 522 RRB, Vanderbilt University, Nashville, TN 37232-6602, USA. jack.roberts@vanderbilt.edu
Fessel
Joshua P
JP
D000818:Animals; D005663:Furans / Q000378:metabolism*; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism*; D015227:Lipid Peroxidation
D005663:Furans; D028421:Isoprostanes