Identification of the peroxisomal beta-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 LTB(4), LTE(4), 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 LTB(4), LTE(4), omega-carboxy-LTB(4), and omega-carboxy-LTE(4) 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 1 we found normal levels of LTB(4), LTE(4), and their oxidation products, indicating that the adrenoleukodystrophy protein and peroxisomal 3-ketoacyl-CoA thiolase are not involved in the metabolic inactivation of LTs.
Ferdinandusse
Sacha
S
Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1105 AZ Amsterdam, The Netherlands.
Meissner
Thomas
T
Wanders
Ronald J A
RJ
Mayatepek
Ertan
E
D000326:Adrenoleukodystrophy / Q000652:urine; D001711:Biotransformation; D002806:Chondrodysplasia Punctata / Q000652:urine; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D017999:Leukotriene E4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000201:enzymology*; D012035:Refsum Disease / Q000652:urine
D015289:Leukotrienes; D007975:Leukotriene B4; D017999:Leukotriene E4