| {Omega}-oxidation of {alpha}-chlorinated fatty acids: identification of {alpha}-chlorinated dicarboxylic acids. | |
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MedLine Citation:
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PMID: 20956542 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Myeloperoxidase-derived HOCl targets tissue- and lipoprotein-associated plasmalogens to generate α-chlorinated fatty aldehydes, including 2-chlorohexadecanal. Under physiological conditions, 2-chlorohexadecanal is oxidized to 2-chlorohexadecanoic acid (2-ClHA). This study demonstrates the catabolism of 2-ClHA by ω-oxidation and subsequent β-oxidation from the ω-end. Mass spectrometric analyses revealed that 2-ClHA is ω-oxidized in the presence of liver microsomes with initial ω-hydroxylation of 2-ClHA. Subsequent oxidation steps were examined in a human hepatocellular cell line (HepG2). Three different α-chlorinated dicarboxylic acids, 2-chlorohexadecane-(1,16)-dioic acid, 2-chlorotetradecane-(1,14)-dioic acid, and 2-chloroadipic acid (2-ClAdA), were identified. Levels of 2-chlorohexadecane-(1,16)-dioic acid, 2-chlorotetradecane-(1,14)-dioic acid, and 2-ClAdA produced by HepG2 cells were dependent on the concentration of 2-ClHA and the incubation time. Synthetic stable isotope-labeled 2-ClHA was used to demonstrate a precursor-product relationship between 2-ClHA and the α-chlorinated dicarboxylic acids. We also report the identification of endogenous 2-ClAdA in human and rat urine and elevations in stable isotope-labeled urinary 2-ClAdA in rats subjected to intraperitoneal administration of stable isotope-labeled 2-ClHA. Furthermore, urinary 2-ClAdA and plasma 2-ClHA levels are increased in LPS-treated rats. Taken together, these data show that 2-ClHA is ω-oxidized to generate α-chlorinated dicarboxylic acids, which include α-chloroadipic acid that is excreted in the urine. |
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Authors:
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Viral V Brahmbhatt; Carolyn J Albert; Dhanalakshmi S Anbukumar; Bryce A Cunningham; William L Neumann; David A Ford |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-18 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-27 Completed Date: 2011-02-09 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 41255-69 Citation Subset: IM |
Affiliation:
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Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, Missouri 63104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chlorine / chemistry* Dicarboxylic Acids / chemistry*, metabolism Fatty Acids / metabolism* Hep G2 Cells Hepatocytes / cytology Humans Mass Spectrometry / methods Microsomes, Liver / metabolism Oxygen / chemistry Palmitic Acids / chemistry Peroxidase / chemistry Peroxidases / chemistry Rabbits Rats |
| Grant Support | |
ID/Acronym/Agency:
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HL074214/HL/NHLBI NIH HHS; HL088073/HL/NHLBI NIH HHS; HL098907/HL/NHLBI NIH HHS; R01 HL074214-05A2/HL/NHLBI NIH HHS; R21 HL088073-02/HL/NHLBI NIH HHS; R21 HL098907-01A1/HL/NHLBI NIH HHS; R21 HL098907-02/HL/NHLBI NIH HHS; RR019232/RR/NCRR NIH HHS; S10 RR019232-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-chlorohexadecanoic acid; 0/Dicarboxylic Acids; 0/Fatty Acids; 0/Palmitic Acids; 7782-44-7/Oxygen; 7782-50-5/Chlorine; EC 1.11.1.-/Peroxidases; EC 1.11.1.7/Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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