Abstract
ABSTRACT: Cyclooxygenase products are metabolized by ω-oxidation as well as β-oxidation. Children with Zellweger syndrome (ZS) are characterized by peroxisome deficiency. To evaluate the role of peroxisomal β-oxidation on cyclooxygenase metabolites, the degradation of endogenous prostanglandin (PG) E2, prostacyclin, and thromboxane (Tx) A2 was assessed in children with ZS (n = 7) and in healthy children (n = 7). PGE2, prostacyclin, TxB2, and their major urinary metabolites 7α-hydroxy-5,11-dioxo-tetranor-prosta-1,16-dioic acid, 2,3-dinor-6-oxo-PGF1α, and 2,3-dinor-TxB2, respectively, were measured in urine by gas chromatography-mass spectrometry/mass spec-trometry. The median excretion of healthy children was 17.9 ng of 7α-hydroxy-5,11-dioxo-tetranor-prosta-1,16-dioic acid/mg creatinine (interquartile range, 6.3 to 19.4 ng/mg), 0.38 ng of 2,3-dinor-6-oxo-PGF1α/mg creatinine (interquartile range, 0.34 to 0.70 ng/mg), and 0.36 ng of 2,3-dinor-TxB2/mg creatinine (interquartile range, 0.14 to 0.54 ng/mg). In contrast, none of these metabolites could be detected in urine of children with ZS (p < 0.002). However, we identified in the urine of these children a new metabolite of PGE2 as 11-hydroxy-9,15-dioxo-prost-5-en-1,20-dioic acid by gas chromatography-mass spectrometry, and we confirmed the presence of 9,11-dihydroxy-15-oxo-prost-5-en-l,20-dioic acid the main urinary metabolite of PGF2α in ZS. Importantly, these two metabolites were only detectable in urine of children with ZS. Furthermore, we found highly elevated amounts of PGE2, 6-oxo-PGF1α, and TxB2 in urine from children with ZS compared with the amounts eliminated by healthy children (all parameters, p < 0.002). The present findings demonstrate an impaired degradation of PG and Tx in ZS on the level of β-oxidation. These data strongly support the hypothesis that prostanoids are exclusively β-oxidized by the peroxisomal pathway in vivo.
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Fauler, J., Tsikas, D., Mayatepek, E. et al. Impaired Degradation of Prostaglandins and Thromboxane in Zellweger Syndrome. Pediatr Res 36, 449–455 (1994). https://doi.org/10.1203/00006450-199410000-00006
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DOI: https://doi.org/10.1203/00006450-199410000-00006
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