Abstract
During aerobic oxidation of docosahexaenoic acid (DHA), soybean lipoxygenase (sLOX) has been shown to form 7,17(S)-dihydro(pero) xydocosahexaenoic acid [7,17(S)-diH(P)DHA] along with its previously described positional isomer, 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z, 15E,19Z-enoic acid. 7,17(S)-diH(P)DHA was also obtained via sLOX-catalyzed oxidation of either 17(S)-hydroperoxydocosahexaenoic acid [17(S)-HPDHA] or 17(S)-hydroxydocosahexaenoic acid [17(S)-HDHA]. The structures of the products were elucidated by normal-phase, reverse-phase, and chiral-phase HPLC analyses and by ultraviolet, NMR, and tandem mass spectroscopy and GC-MS. 7,17(S)-diH(P)DHA was shown to have 4Z,8E,10Z,13Z,15E,19Z geometry of the double bonds. In addition, a compound apparently identical to the sLOX-derived 7,17(S)-diH(P)DHA was produced by another enzyme, potato tuber LOX, in the reactions of oxygenation of either 17(S)-HPDHA or 17(S)-HDHA. All of the dihydroxydocosahexaenoic acids (diHDHAs) formed by either of the enzymes were clearly produced through double lipoxygenation of the corresponding substrate. 7,17(S)-diHDHA inhibited human recombinant 5-lipoxygenase in the reaction of arachidonic acid (AA) oxidation. In standard conditions with 100 μM AA as substrate, the IC50 value for 7,17(S)-diHDHA was found to be 7 μM, whereas IC50 for 10,17(S)-DiHDHA was 15 μM. Similar inhibition by the diHDHAs was observed with sLOX, a quintessential 15LOX, although the strongest inhibition was produced by 10,17(S)-diHDHA (IC50 = 4 μM). Inhibition of sLOX by 7,17(S)-diHDHA was slightly less potent, with an IC50 value of 9 μM. These findings suggest that 7,17(S)-diHDHA along with its 10,17(S) counterpart might have anti-inflammatory and anticancer activities, which could be exerted, at least in part, through direct inhibition of 5LOX and 15LOX.
Original language | English (US) |
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Pages (from-to) | 2462-2474 |
Number of pages | 13 |
Journal | Journal of lipid research |
Volume | 47 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2006 |
Keywords
- 10,17-dihydroxydocosahexaenoic acid
- 7,17-dihydroxydocosahexaenoic acid
- Docosahexaenoic acid
- Double lipoxygenation
- Neuroprotectins D1 and D5
- Protectins D1 and D5
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology