Microsomal fatty aldehyde dehydrogenase catalyzes the oxidation of aliphatic aldehyde derived from ether glycerolipid catabolism: implications for Sjogren-Larsson syndrome

The enzyme that catalyzes the oxidation of fatty aldehyde derived from ethe r glycerolipid catabolism has not been identified. To determine whether mic rosomal fatty aldehyde dehydrogenase (FALDH) is responsible, we investigate d the metabolism of 1-O-[9,10-H-3-octadecyl]-glycerol ([H-3]OG) in FALDH-de ficient cultured cells from patients with Sjogren-Larsson syndrome (SLS) an d in mutant Chinese hamster ovary (CHO) cells. Intact fibroblasts from SLS patients incubated with [H-3]OG showed a selective deficiency (38 +/- 7% of normal) in the incorporation of radioactivity into fatty acid, but no decr ease in incorporation of radioactivity into fatty alcohol, total lipids and phosphatidylethanolamine (PE). Consistent with fatty aldehyde accumulation , incorporation of radioactivity into N-alkyl-phosphatidylethanolamine, whi ch is derived from Schiff base formation of free aldehyde with PE, was 4-fo ld higher in SLS fibroblasts compared to normal controls. Similar results w ere seen with SLS keratinocytes, whereas FALDH-deficient CHO cells showed a more profound reduction in radioactive fatty acid to 12 +/- 2% of normal. These results implicate FALDH in the oxidation of ether-derived fatty aldeh yde in human and rodent cells. Metabolism of ether glycerolipids is a previ ously unrecognized source of fatty aldehyde that may contribute to the path ogenesis of SLS. (C) 2000 Elsevier Science B.V. All rights reserved.