On the structure and synthesis of neuroprotectin D1, a novel anti-inflammatory compound of the docosahexaenoic acid family

Igor A Butovich

doi:10.1194/jlr.c500015-jlr200

Igor A Butovich

Open Access

https://doi.org/10.1194/jlr.c500015-jlr200

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Abstract

Potato tuber lipoxygenase was shown to convert 17(S)-hydro(pero)xydocasahexaenoic acid in 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid [10,17(S)-diHDHA] which was formed apparently through a double lipoxygenation mechanism. No traces of 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13E,15Z,19Z-enoic acid were found among the reaction products. It is very likely that a described earlier "neuroprotectin D1" [or "10,17(S)docosatriene"], a novel and potent anti-inflammatory compound derived from docosahexaenoic acid, was, in fact, 10,17(S)-dihydroxydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid formed through a double lipoxygenation mechanism instead of a previously thought epoxidation/isomerization mechanism.

Highlights

Potato tuber lipoxygenase was shown to convert 17(S)-hydro(pero)xydocasahexaenoic acid in 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid [10,17(S)-diHDHA] which was formed apparently through a double lipoxygenation mechanism
My colleagues and I published the results of our study of potato tuber lipoxygenase (ptLOX)-catalyzed transformations of DHA, 17(S)-hydroperoxydocosahexaenoic acid [17(S)-HPDHA], and 17(S)-hydroxydocosahexaenoic acid [17(S)-HDHA] [8]
The ptLOX-catalyzed oxidation of DHA unexpectedly led to two novel oxylipins, 10(S)-HDHA and 10(S), 20-diHDHA, that were not described before, whereas in the reactions with 17(S)-HPDHA or 17(S)-HDHA, another pair of products, 7,17(S)-diH(P)DHA and 10,17(S)diH(P)DHA, were formed, apparently through a double lipoxygenation mechanism

Summary

Introduction

Potato tuber lipoxygenase was shown to convert 17(S)-hydro(pero)xydocasahexaenoic acid in 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid [10,17(S)-diHDHA] which was formed apparently through a double lipoxygenation mechanism. Several papers were published that described a novel class of potent anti-inflammatory lipid compounds formed from docosahexaenoic acid (␻-3 C22:6; DHA) by various cells and isolated enzymes [1,2,3,4,5,6]. The compound was termed 10,17(S)-docosatriene (and neuroprotectin D1) and was proposed to be 10,17(S)-dihydroxydocosahexa-4Z,7Z,11E,13E,15Z,19Z-enoic acid.

Results

Conclusion