Increased urinary excretion of LTB4 and omega-carboxy-LTB4 in patients with Zellweger syndrome.
The metabolic inactivation of leukotrienes proceeds by beta-oxidation from the omega-end. We investigated the importance of peroxisomes and mitochondria in LTB4 oxidation in vivo. LTB4 and its oxidation products were analysed after high-performance liquid chromatography separation by immunoassays and gas chromatography-mass spectrometry in the urine of patients with Zellweger syndrome, patients with long-chain acyl CoA dehydrogenase deficiency, and healthy controls. LTB4 (median 97; range 35-238 nmol/mol creatinine) and its omega-oxidation product omega-carboxy-LTB4 (median 898; range 267-4583 nmol/mol creatinine) were present and significantly increased in the urine of all patients with Zellweger syndrome compared to the controls (P <0.01). In contrast, LTB4 and omega-carboxy-LTB4 were below the detection limit (< 5 nmol/ mol creatinine) in patients with long-chain acyl CoA dehydrogenase deficiency and healthy controls. The beta-oxidation product omega-carboxy-tetranor-LTB3 was neither detectable in the urine of patients with Zellweger syndrome, patients with long-chain acyl CoA dehydrogenase deficiency nor in the controls (< 5 nmol/mol creatinine). Analysis of urinary leukotrienes represents an additional diagnostic tool in peroxisome deficiency disorders. Furthermore, these results clearly underline the essential role of peroxisomes in the oxidation of LTB4 in humans.
Mayatepek
E
E
Division of Metabolic Diseases, University Children's Hospital, Heidelberg, Germany. ertan_mayatepek@med.uni-heidelberg.de
Flock
B
B
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007223:Infant; D007975:Leukotriene B4 / Q000652:urine*; D008830:Microbodies / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D015211:Zellweger Syndrome / Q000652:urine*
D007975:Leukotriene B4; D044942:Acyl-CoA Dehydrogenase, Long-Chain