Reactome | ALOXE3 isomerises 12R-HpETE to HXA3

ALOXE3 isomerises 12R-HpETE to HXA3

Stable Identifier

R-HSA-8942208

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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 arachidonate and linoleate 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 Zheng, Y, Yin, H, Boeglin, WE, Elias, PM, Crumrine, D, Beier, DR, Brash, AR	J. Biol. Chem.	2011
15629692	Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3 Yu, Z, Schneider, C, Boeglin, WE, Brash, AR	Biochim. Biophys. Acta	2005
12881489	The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase Yu, Z, Schneider, C, Boeglin, WE, Marnett, LJ, Brash, AR	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 Wang, T, Xu, C, Zhou, X, Li, C, Zhang, H, Lian, BQ, Lee, JJ, Shen, J, Liu, Y, Lian, CG	Int J Mol Sci	2015