Demonstration
of HNE-related Aldehyde Formation via
Lipoxygenase-catalyzed Synthesis of a <i>bis</i>-Allylic Dihydroperoxide Intermediate
Jing Jin
Yuxiang Zheng
Alan R. Brash
10.1021/tx4000396.s001
https://acs.figshare.com/articles/journal_contribution/Demonstration_of_HNE_related_Aldehyde_Formation_via_Lipoxygenase_catalyzed_Synthesis_of_a_i_bis_i_Allylic_Dihydroperoxide_Intermediate/2405059
One 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 8<i>R</i>-lipoxygenase (8<i>R</i>-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 8<i>R</i>-LOX formed initially 8<i>R</i>-hydroperoxy-eicosatetraenoic
acid (8<i>R</i>-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 8<i>R</i>-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 <i>in vivo</i>.
2013-06-17 00:00:00
HNE
LOX iron
enone products
pathway
arachidonic acid
synthesis
acid dihydroperoxide
NDGA