Studying fatty aldehyde metabolism in living cells with pyrene-labeled compounds

The lack of fatty aldehyde dehydrogenase function in Sjögren Larsson Syndrome(SLS) patient cells not only impairs the conversion of fatty aldehydes into theircorresponding fatty acid but also has an effect on connected pathways. Alteration ofthe lipid profile in these cells is thought to be responsible for severe symptomssuch as ichtyosis, mental retardation, and spasticity. Here we present a novelapproach to examine fatty aldehyde metabolism in a time-dependent manner by measuringpyrene-labeled fatty aldehyde, fatty alcohol, fatty acid, and alkylglycerol in theculture medium of living cells using HPLC separation and fluorescence detection. Ourresults show that in fibroblasts from SLS patients, fatty aldehyde is notaccumulating but is converted readily into fatty alcohol. In control cells, incontrast, exclusively the corresponding fatty acid is formed. SLS patient cells didnot display a hypersensitivity toward hexadecanal or hexadecanol, but 3-fold lowerconcentrations of the fatty alcohol than the corresponding fatty aldehyde were neededto induce toxicity in SLS patient and in control cells.