Energetics of the biosynthesis of cyclopentenones from unsaturated fatty acids

Abstract

Polyunsaturated fatty acids like linolenic acid or arachidonic acid upon enzymatic hydroxylation (lipoxygenases) can lead to corresponding hydroperoxides. Their dehydration gave rise to vinyl allene oxides, which cyclized into cyclopentenones, precursors of jasmonic acid or prostanoids.We have studied the energetics of these cascade reactions to determine their thermodynamic parameters and reveal the key steps. The formation of hydroperoxydes from polyunsaturated fatty acids and triplet dioxygen appeared as a surprisingly slightly exergonic reaction (∼6–15 kcal mol−1). In contrast, the cumulated following reactions were highly exergonic (∼95–100 kcal mol−1). Cyclization of the (E)-vinyl allene oxides occurred with an activation barrier of ∼23 kcal mol−1, while cyclization of the (Z)-isomer required two steps: first isomerization into vinylcyclopropanone (TS: ∼20 kcal mol−1), and then isomerization of the latter into cyclopentenone (TS: ∼18 kcal mol−1).