Mayatepek E, Flock B
Division of Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
Clin Chim Acta. 1999 Apr;282(1-2):151-5. doi: 10.1016/s0009-8981(99)00015-7.
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.
白三烯的代谢失活通过从ω端进行β氧化来实现。我们研究了过氧化物酶体和线粒体在体内LTB4氧化中的重要性。通过免疫测定和气相色谱 - 质谱联用技术，在患有泽尔韦格综合征的患者、患有长链酰基辅酶A脱氢酶缺乏症的患者以及健康对照者的尿液中，对LTB4及其氧化产物进行了高效液相色谱分离后的分析。与对照组相比，所有泽尔韦格综合征患者尿液中均存在LTB4（中位数97；范围35 - 238 nmol/mol肌酐）及其ω氧化产物ω-羧基-LTB4（中位数898；范围267 - 4583 nmol/mol肌酐），且显著增加（P <0.01）。相比之下，长链酰基辅酶A脱氢酶缺乏症患者和健康对照者尿液中的LTB4和ω-羧基-LTB4低于检测限（<5 nmol/mol肌酐）。在泽尔韦格综合征患者、长链酰基辅酶A脱氢酶缺乏症患者以及对照组的尿液中均未检测到β氧化产物ω-羧基-四去甲-LTB3（<5 nmol/mol肌酐）。尿液白三烯分析是过氧化物酶体缺乏症的一种额外诊断工具。此外，这些结果清楚地强调了过氧化物酶体在人类LTB4氧化中的重要作用。
