ALOXE3 isomerises 12R-HpETE to HXA3

Stable Identifier
Reaction [transition]
Homo sapiens
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Hydroperoxide isomerase (ALOXE3, e-LOX-3) is a non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyses the isomerisation of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into epoxyalcohols (Yu et al. 2003).
In the skin, ALOXE3 acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins, important for the maintenance of the skin permeability barrier and protection against water loss. Loss-of-function mutations in ALOX12B and ALOXE3 represent the second most common cause of autosomal recessive congenital ichthyosis, a hereditary disorder of keratinization (Yu et al. 2005, Wang et al. 2015). Targeted disruption of these genes in mice resulted in neonatal death due to a severely impaired permeability barrier function (Zheng et al. 2011).

Literature References
PubMed ID Title Journal Year
21558561 Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope

Brash, AR, Crumrine, D, Beier, DR, Yin, H, Boeglin, WE, Elias, PM, Zheng, Y

J. Biol. Chem. 2011
15629692 Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3

Brash, AR, Boeglin, WE, Schneider, C, Yu, Z

Biochim. Biophys. Acta 2005
12881489 The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase

Brash, AR, Boeglin, WE, Marnett, LJ, Schneider, C, Yu, Z

Proc. Natl. Acad. Sci. U.S.A. 2003
26370990 Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi's Granuloma: The Consequences of Skin Barrier Dysfunction

Liu, Y, Li, C, Lian, BQ, Zhang, H, Xu, C, Shen, J, Lee, JJ, Zhou, X, Lian, CG, Wang, T

Int J Mol Sci 2015
Catalyst Activity

hepoxilin A3 synthase activity of ALOXE3 [cytosol]

Orthologous Events
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