Interactions of cholesterol and cholesterol sulfate with free fatty acids: possible relevance for the pathogenesis of recessive X-linked ichthyosis.
Whereas the stratum corneum contains large amounts of unesterified cholesterol and minimal amounts of cholesterol sulfate, in recessive X-linked ichthyosis (RXLI), levels of cholesterol decrease while cholesterol sulfate content increases. To study the molecular basis for abnormal shedding in RXLI, we compared the interaction of cholesterol and cholesterol sulfate with the free fatty acid, hexadecanoic acid, by differential scanning calorimetry (DSC). While cholesterol and the free fatty acid formed a eutectic mixture, such an interaction did not occur upon mixing of cholesterol sulfate with hexadecanoic acid. In addition, and unexpectedly, free cholesterol appeared to undergo progressive autoxidation during repeated DSC measurements at only slightly supraphysiologic temperatures. These studies may provide a molecular mechanism for the abnormal desquamation that occurs in RXLI. The regular formation of oxidation products of cholesterol observed here, if matched by equivalent molecular events in vivo, may have important implications for epidermal pathophysiology.
D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006801:Humans; D007057:Ichthyosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D010169:Palmitic Acids / Q000378:metabolism; D014960:X Chromosome
D002788:Cholesterol Esters; D005230:Fatty Acids, Nonesterified; D010169:Palmitic Acids; D002784:Cholesterol; C007045:cholesteryl sulfate