Essential and Skin-deep: The Beauty of Epidermal Lipoxygenases♦


Papers of the Week

Essential and Skin-deep: The Beauty of Epidermal
Lipoxygenases�
� See referenced article, J. Biol. Chem. 2011, 286, 24046 –24056

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

As defined nearly a century ago, dietary deficiencies in polyunsaturated fatty acids (PUFAs)
are hallmarked by the appearance of dry, scaly skin. Two epidermis-specific enzymes that act
on PUFAs are the lipoxygenases ALOX12B and ALOXE3, and just within the past decade, a
deficiency in either of these has been associated with disease states characterized by dry, scaly
skin. The biochemical mysteries that connect these two observations and explain lipoxygenase
functionality in skin hydration have remained obscure, but in their JBC Paper of the Week,
Zheng et al. elucidate a conceptual framework for understanding how ALOX12B and ALOXE3
function concertedly to maintain the epidermal water barrier. Through high-resolution spec-
troscopic methods, the authors show that the enzymes together oxidize the PUFA moiety of a
PUFA-ceramide linkage (i.e. the linoleoyl moiety of O-linoleoyl-�-hydroxyceramides). More-
over, the sequential oxygenase reactions preface the hydrolytic release of the oxidized linoleoyl
moiety from the ceramide component, the latter of which ultimately participates in the
microarchitecture of the epidermal water barrier.

DOI 10.1074/jbc.P111.251496

e99954

OOO

O

Lamellar
Lipids

outside

Cross-linked proteins inside
Cornified Envelope (CE)

O
O

OH
Glc-O

Early Stage of Barrier Formation

Fused
Lamellar

Lipids

Covalent linkage couples
CLE to CE and seals barrier

Late Stages of Barrier Formation

covalent
coupling
to protein

O

HN
OH

HO

O

O

HN
OH

HO

O

O

HN
OH

HO

O

12R-LOX eLOX3

“oxygen
signal”

hydrolysis
of oxidized
linoleate

O

HN
OH

HO

O

OH

HN
OH

HO

O

oxidation
of linoleate
in ceramide

CLE

HN
O

O

OH

Skin barrier formation: essential fatty acids linked to essential enzyme activities.

This is an Open Access article under the CC BY license.

http://creativecommons.org/licenses/by/4.0/

	Essential and Skin-deep: The Beauty of Epidermal Lipoxygenases♦