Roberts L Jackson, Fessel Joshua P
Departments of Pharmacology and Medicine, 522 RRB, Vanderbilt University, Nashville, TN 37232-6602, USA.
Chem Phys Lipids. 2004 Mar;128(1-2):173-86. doi: 10.1016/j.chemphyslip.2003.09.016.
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.
F2-异前列腺素是一类与前列腺素F2类似的化合物，它们通过自由基介导的花生四烯酸过氧化反应非酶促形成。异前列腺素形成途径中的中间体是不稳定的前列腺素H2类似双环内过氧化物（H2-异前列腺素），其可还原为F2-异前列腺素，并且在体内还会发生重排以形成E环和D环异前列腺素、异血栓素以及高反应性无环γ-酮醛（异缩醛）。二十二碳六烯酸（C22:6ω3）在大脑神经元中高度富集，并且极易被氧化。自由基介导的二十二碳六烯酸氧化会导致类异前列腺素化合物（神经前列腺素）的形成。已证实在体内会产生F4-和E4/D4-神经前列腺素以及神经缩醛。最后，我们最近发现了一种脂质过氧化的新途径，该途径可形成具有取代四氢呋喃环的化合物（异呋喃）。氧浓度会差异性地调节异前列腺素和异呋喃的形成；在高氧浓度下，异呋喃的形成占优势，而异前列腺素的形成则受到抑制。
