Open AccessThe Biochemistry of the Isoprostane, Neuroprostane, and Isofuran Pathways of Lipid Peroxidation
Author(s) -
Roberts L. Jackson,
Fessel Joshua P.,
Davies Sean S.
Publication year - 2005
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2005.tb00511.x
Subject(s) - isoprostanes , isoprostane , chemistry , lipid peroxidation , arachidonic acid , biochemistry , docosahexaenoic acid , reactive oxygen species , oxidative stress , polyunsaturated fatty acid , fatty acid , enzyme
Isoprostanes are prostaglandin‐like compounds that are formed non‐enzymatically by free radical‐catalyzed peroxidation of arachidonic acid (C20:4ω6). Intermediates in the pathway of the formation of isoprostanes are labile prostaglandin H 2 ‐like bicyclic endoperoxides (H 2 ‐isoprostanes). H 2 ‐isoprostanes are reduced to form F‐ring isoprostanes (F 2 ‐isoprostanes), but they also undergo chemical rearrangement in vivo to form E 2 ‐ and D 2 ‐isoprostanes, isothromboxanes, and highly reactive acyclic γ‐ketoaldehdyes (isoketals). E 2 ‐ and D 2 ‐isoprostanes also undergo dehydration in vivo to form cyclopentenone A 2 ‐ and J 2 ‐isoprostanes. Docosahexaenoic acid (C22:6ω3) 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). F 4 ‐,D 4 ‐,E 4 ‐,A 4 ‐,and J 4 ‐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.