Alkaline ceramidase 1

Definition:

Endoplasmic reticulum ceramidase that catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids at alkaline pH. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. Exhibits a strong substrate specificity towards the natural stereoisomer of ceramides with D-erythro-sphingosine as a backbone and has a higher activity towards very long-chain unsaturated fatty acids like the C24:1-ceramide. May also hydrolyze dihydroceramides to produce dihydrosphingosine. ACER1 is a skin-specific ceramidase that regulates the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes and more generally plays an important role in skin homeostasis.

References:

[1]. Ruijuan Xu, et al. Role of alkaline ceramidases in the generation of sphingosine and its phosphate in erythrocytes. FASEB J. 2010 Jul;24(7):2507-15. [Content Brief]

[2]. Wei Sun, et al. Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes. J Invest Dermatol. 2008 Feb;128(2):389-97. [Content Brief]

[3]. Zhehao Mao, et al. Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells. J Biol Chem. 2010 Sep 17;285(38):29078-90. [Content Brief]

[4]. Cungui Mao, et al. Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. J Biol Chem. 2003 Aug 15;278(33):31184-91. [Content Brief]

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