J Dermatol Sci. 2008 Aug;51(2):77-87. doi: 10.1016/j.jdermsci.2008.01.002. Epub 2008 Mar 10.
Omega-O-acylceramide, a lipid essential for mammalian survival.
Abstract
The
prevention of water loss through the skin is critical for terrestrial
mammalian species. This function is served by the epidermal permeability
barrier, which resides primarily in the extracellular domains of the
stratum corneum, the outermost layer of skin, and its highly ordered
lamellar membranes composed primarily of free fatty acids, cholesterol,
and ceramides
(Cer). The dominant lipids in these lamellae are Cer, which comprise a
heterogeneous group of chemically distinct species. One particular
subfamily of Cer, which is unique to the outer layers of the epidermis
of terrestrial mammals, is omega (omega)-O-acylCer (or acylCer). Myriad
evidence suggests that these acylCer play critical roles in barrier
function. The formation of these epidermal acylCer requires several
metabolic steps, including synthesis of , VLCFA
omega-hydroxylation of the fatty acids, and esterification at the
omega-hydroxy group with primarily linoleic acid. The authors previously
demonstrated that a cytochrome P-450-type enzyme is involved in
omega-hydroxylation during acylCer generation and that inhibition of
omega-hydroxylation leads to a barrier abnormality in murine epidermis.
More recently, we discovered that lack of normal elongation of very long
chain fatty acid (or ELOVL) 4 function in mutant ELOVL4 knock-in mice
causes acylCer deficiency associated with abnormal barrier formation and
neonatal lethality. These results indicate not only that acylCer are
critical lipid components for mammalian survival, but also that
keratinocytes deploy a complex metabolic pathway leading to the
formation of these unique Cer.
- PMID:
- 18329855
- [PubMed - indexed for MEDLINE]
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