Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity.
Lipid metabolism was studied in cultured skin fibroblasts from patients with the inherited disorder, Sjögren-Larsson syndrome (SLS). Intact SLS fibroblasts incubated in the presence of [1-14C]palmitate accumulated more radioactive hexadecanol than did normal cells, whereas incorporation of radioactivity into other cellular lipids was unaltered. The hexadecanol content of SLS fibroblasts was abnormally elevated. Hexadecanol accumulation was not due to increased fatty alcohol synthesis nor its deficient utilization for glycerol ether synthesis. The half-life of intracellular hexadecanol loaded into SLS fibroblasts was increased (70 min) compared with normal (15 min), and intact SLS fibroblasts showed impaired oxidation of [14C]-hexadecanol to fatty acid. Fatty alcohol:NAD+ oxidoreductase, the enzyme catalyzing this reaction, was deficient in SLS fibroblasts. Mean total activity in SLS fibroblasts (n = 5) was 13% of that in normal fibroblasts, and palmitoyl CoA-inhibitable activity was 1% of normal. Fibroblasts from two obligate SLS heterozygotes had enzyme activities intermediate between that in normal fibroblasts and individuals with SLS. These results suggest that the primary defect in SLS is deficiency of fatty alcohol:NAD+ oxidoreductase. SLS represents the first inherited disorder in man associated with an isolated abnormality in fatty alcohol metabolism.
Rizzo
W B
WB
Department of Pediatrics, Medical College of Virginia, Richmond 23298.
Dammann
A L
AL
Craft
D A
DA
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D002478:Cells, Cultured; D005233:Fatty Alcohols / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007057:Ichthyosis / Q000201:enzymology / Q000378:metabolism*
D005233:Fatty Alcohols; C005031:cetyl alcohol; D015094:3-Hydroxyacyl CoA Dehydrogenases