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Demonstration of HNE-related Aldehyde Formation via Lipoxygenase-catalyzed Synthesis of a bis-Allylic Dihydroperoxide Intermediate
journal contribution
posted on 2013-06-17, 00:00 authored by Jing Jin, Yuxiang Zheng, Alan R. BrashOne of the proposed pathways to the
synthesis of 4-hydroxy-nonenal
(HNE) and related aldehydes entails formation of an intermediate bis-allylic
fatty acid dihydroperoxide. As a first direct demonstration of such
a pathway and proof of principle, herein we show that 8R-lipoxygenase (8R-LOX) catalyzes the enzymatic production
of the HNE-like product (11-oxo-8-hydroperoxy-undeca-5,9-dienoic acid)
via synthesis of 8,11-dihydroperoxy-eicosa-5,9,12,14-tetraenoic acid
intermediate. Incubation of arachidonic acid with 8R-LOX formed initially 8R-hydroperoxy-eicosatetraenoic
acid (8R-HPETE), which was further converted to a
mixture of products including a prominent HPNE-like enone. A new bis-allylic
dihydroperoxide was trapped when the incubation was repeated on ice.
Reincubation of this intermediate with 8R-LOX successfully
demonstrated its conversion to the enone products, and this reaction
was greatly accelerated by coincubation with NDGA, a reductant of
the LOX iron. These findings identify a plausible mechanism that could
contribute to the production of 4-hydroxy-alkenals in vivo.