Specificities of Human and Rat Brain Enzymes of Cholesterol Ester Metabolism Toward Very Long Chain Fatty Acids: Implication for Biochemical Pathogenesis of Adrenoleukodystrophy

Abstract: Specificities of the cholesterol-esterifying enzyme and the three cholesterol esterases in rat brain with respect to the chain length of fatty acids were examined. For each of the hydrolases, activities toward cholesteryl lignocerate and cerotate were generally less than 1% of that toward cholesteryl oleate. However, both lignoceric and cerotic acids were esterified at rates approximately 10% of that for oleic acid. In postmortem human control and adrenoleukodystrophy brains, the esterifying activity toward cerotic acid was on the average 25% of that toward oleic acid. The abnormal accumulation of cholesterol esters with very long chain fatty acids observed in adrenoleukodystrophy can therefore occur in the absence of deficient activities of the cholesterol esterases, if the free fatty acid pool of the brain contains an abnormal amount of very long chain fatty acids.