Document Detail


Peroxisomal chain-shortening of thromboxane B2: evidence for impaired degradation of thromboxane B2 in Zellweger syndrome.
MedLine Citation:
PMID:  8371058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have shown that rat liver peroxisomes can chain-shorten prostaglandins to dinor- and tetranor-metabolites. In a recent in vivo study we could demonstrate that peroxisomes are of major importance for chain-shortening of prostaglandin F2 alpha in humans (1991, Diczfalusy et al. J. Clin. Invest. 88:978-984). This was shown by identifying the major urinary metabolites of radiolabeled prostaglandin F2 alpha given intravenously to a patient lacking functional peroxisomes (Zellweger syndrome). In the present investigation we have studied the peroxisomal chain-shortening of thromboxane B2, a compound structurally related to prostaglandins. Isolated rat liver peroxisomes oxidized thromboxane B2 to a chain-shortened metabolite in an NAD(+)-dependent reaction. The metabolite was identified as 9,11,15-trihydroxy-2,3,4,5-tetranor-thromb-13-enoic acid (tetranor-thromboxane B1). The urinary excretion of the major beta-oxidized metabolites of thromboxane B2 and prostacyclin was determined in three Zellweger patients and six age-matched controls. The controls excreted on an average 1.7 and 1.1 ng/mg creatinine of 2,3-dinorthromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, respectively. In none of the three Zellweger patients could these dinor-metabolites be detected, i.e., the urinary excretion was less than 0.2 ng/mg creatinine. This shows that peroxisomes play an important role in the degradation of the carboxyl side chain of thromboxane B2 in vivo.
Authors:
U Diczfalusy; O Vesterqvist; B F Kase; E Lund; S E Alexson
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of lipid research     Volume:  34     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-10-08     Completed Date:  1993-10-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1107-13     Citation Subset:  IM    
Affiliation:
Department of Clinical Chemistry, Huddinge University Hospital, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Epoprostenol / urine
Microbodies / metabolism*
Oxidation-Reduction
Rats
Reference Values
Thromboxane B2 / metabolism*,  urine
Zellweger Syndrome / metabolism*,  urine
Chemical
Reg. No./Substance:
35121-78-9/Epoprostenol; 54397-85-2/Thromboxane B2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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