Lipids appear to play a critical role as regulators of stratum corneum desquamation. In this study, we observed discrete
lipid phase transitions at physiologic temperatures in both normal human scale (NHS) and in
lipid extracts of NHS by differential scanning calorimetry. In contrast, such thermal transitions were not observed in recessive
x-linked ichthyosis scale (RXLIS). To gain further insight into the molecular basis of the
lipid phase transitions in NHS vs. RXLIS, comparable samples were evaluated by electron spin resonance, utilizing the perdeuterated probe,
di-t-butyl nitroxide. Upon electron spin resonance analysis, both NHS and RXLIS demonstrated thermal phase transitions in the physiologic range; however, the nature of the
lipid environments in each type varied. Whereas the environment of the spin probe was more polar in NHS than in RXLIS, the spin probe partitioned into a more "fluid" environment in RXLIS; i.e., the spin probe was more mobile in RXLIS than in NHS
lipid matrices. Because an alteration in the
cholesteryl sulfate:
cholesterol ratio is the primary
lipid abnormality in RXLIS, model
cholesterol-
fatty acid-
cholesteryl sulfate mixtures were prepared in proportion to the
lipid composition of NHS and RXLIS. Differences were observed in both thermal transitions and in
lipid microenvironments in these mixtures that paralleled those observed in scale samples. Based on these results, a model is proposed that invokes abnormal hydrogen bonding, due to increased
cholesteryl sulfate, as the mechanism for the abnormal desquamation in recessive
X-linked ichthyosis.