Identification of the peroxisomal β-oxidation enzymes involved in the degradation of leukotrienes

Leukotrienes (LTs) are metabolically inactivated via omega-oxidation and subsequent beta-oxidation from the omega-end. This beta-oxidation process takes place in peroxisomes. In this study we investigated the role of different enzymes involved in peroxisomal beta-oxidation in the degradation of LTs. We analyzed LTB4, LTE4, and their oxidation products in urine of patients with Infantile Refsum's disease (IRD), D-bifunctional protein (DBP) deficiency, Rhizomelic Chondrodysplasia Punctata (RCDP) type 1, and X-linked adrenoleukodystrophy (XALD). We found that patients with IRD and DBP deficiencies excrete increased amounts of LTB4, LTE4, omega-carboxy-LTB4, and co-carboxy-LTE4 in their urine, whereas the beta-oxidation products were not detectable. These results show that DBP plays an essential role in the degradation of LTs. In urine of patients with XALD and RCDP type I we found normal levels of LTB4, LTE4, and their oxidation products, indicating that the adrenoleukodystrophy protein and peroxisomal 3-ketoacyl-CoA thiolase are not involved in the metabolic inactivation of LTs. (C) 2002 Elsevier Science (USA). All rights reserved.