title: Studying fatty aldehyde metabolism in living cells with pyrene-labeled compounds.
abstract: The lack of fatty aldehyde dehydrogenase function in Sjögren Larsson Syndrome (SLS) patient cells not only impairs the conversion of fatty aldehydes into their corresponding fatty acid but also has an effect on connected pathways. Alteration of the lipid profile in these cells is thought to be responsible for severe symptoms such as ichtyosis, mental retardation, and spasticity. Here we present a novel approach to examine fatty aldehyde metabolism in a time-dependent manner by measuring pyrene-labeled fatty aldehyde, fatty alcohol, fatty acid, and alkylglycerol in the culture medium of living cells using HPLC separation and fluorescence detection. Our results show that in fibroblasts from SLS patients, fatty aldehyde is not accumulating but is converted readily into fatty alcohol. In control cells, in contrast, exclusively the corresponding fatty acid is formed. SLS patient cells did not display a hypersensitivity toward hexadecanal or hexadecanol, but 3-fold lower concentrations of the fatty alcohol than the corresponding fatty aldehyde were needed to induce toxicity in SLS patient and in control cells.
authors.affiliation: Division of Biological Chemistry, Biocenter,  Innsbruck Medical University, 6020 Innsbruck,  Austria.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Keller
authors.forename: Katrin
authors.initials: K
authors.lastname: Watschinger
authors.forename: Karsten
authors.initials: K
authors.lastname: Lange
authors.forename: Georg
authors.initials: G
authors.lastname: Golderer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Werner-Felmayer
authors.forename: Albin
authors.initials: A
authors.lastname: Hermetter
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Werner
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011721:Pyrenes / Q000737:chemistry* / Q000378:metabolism; D016111:Sjogren-Larsson Syndrome / Q000378:metabolism* / Q000473:pathology; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000447:Aldehydes; D005227:Fatty Acids; D011721:Pyrenes; C001634:fatty aldehyde; C030984:pyrene; D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase