Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.

Epidermal ceramides (Cer) comprise a heteroge- neous family of seven species, including two unique v -hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsi- ble for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer pro- duction. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphin- gomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of b -glucocerebrosidase. Using gas chromatography- mass spectrometry, fast atom bombardment-mass spectrome- try, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with dis- tinctive amide-linked ( N -acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C 22-26 ), short-chain FA (SM-2; primarily C 16 ), and short-chain a -hydroxy FA (SM-3; C 16-18 ). In contrast, only trace quantities of v -hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphin- gosine was not detected. Comparison of these SM with cor- responding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. More- over, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indi- cate that two epidermal SM, that is, SM-1 and SM-3, are im- portant precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, includ- ing the v -hydroxy Cer species, do not derive from SM. — Uchida, Y., M. Hara, H. Nishio, E. Sidransky, S. Inoue, F. Otsuka, A. Suzuki, P. M. Elias, W. M. Holleran, and S. Hamanaka. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J. Lipid Res. 2000. 41: 2071-2082.