{"corpus_id":28494524,"paper_sha":"8637b37049478848e84e166d85318c8ae9eb0fce","doi":"10.1074/jbc.M110.147157","arxiv_id":null,"pmid":20956542,"pmcid":"PMC3009851","mag_id":2026332325,"dblp_id":null,"acl_id":null,"title":"{Omega}-oxidation of {alpha}-chlorinated fatty acids: identification of {alpha}-chlorinated dicarboxylic acids.","year":2010,"publication_date":"2010-12-31","venue":"Journal of Biological Chemistry","journal":{"name":"The Journal of biological chemistry","pages":"\n          41255-69\n        ","volume":"285 53"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":53,"citation_count":25,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Chlorine","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"}],"ui":"D002713"},{"d":"Dicarboxylic Acids","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D003998"},{"d":"Fatty Acids","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D005227"},{"d":"Hep G2 Cells","mj":false,"ui":"D056945"},{"d":"Hepatocytes","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"}],"ui":"D022781"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Mass Spectrometry","mj":false,"qs":[{"q":"methods","mj":false,"ui":"Q000379"}],"ui":"D013058"},{"d":"Microsomes, Liver","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D008862"},{"d":"Oxygen","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D010100"},{"d":"Palmitic Acids","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D010169"},{"d":"Peroxidase","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D009195"},{"d":"Peroxidases","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D010544"},{"d":"Rabbits","mj":false,"ui":"D011817"},{"d":"Rats","mj":false,"ui":"D051381"}],"chemicals":[{"n":"2-chlorohexadecanoic acid","ui":"C532464","reg":"0"},{"n":"Dicarboxylic Acids","ui":"D003998","reg":"0"},{"n":"Fatty Acids","ui":"D005227","reg":"0"},{"n":"Palmitic Acids","ui":"D010169","reg":"0"},{"n":"Chlorine","ui":"D002713","reg":"4R7X1O2820"},{"n":"Peroxidases","ui":"D010544","reg":"EC 1.11.1.-"},{"n":"Peroxidase","ui":"D009195","reg":"EC 1.11.1.7"},{"n":"Oxygen","ui":"D010100","reg":"S88TT14065"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.jbc.org/article/S0021925819761092/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/8637b37049478848e84e166d85318c8ae9eb0fce","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"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.","claims":[{"public_id":"cl_4b91ee0b9efb7c4abc8f24fa06f2da48","status":"active","text":"2-chlorohexadecanoic acid is catabolized by ω-oxidation followed by β-oxidation from the ω-end.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_4b91ee0b9efb7c4abc8f24fa06f2da48"},{"public_id":"cl_61b3c8106b20b6e6d08f0e972acd42bd","status":"active","text":"Endogenous 2-chloroadipic acid is present in human and rat urine, and urinary 2-chloroadipic acid increases after intraperitoneal administration of stable isotope-labeled 2-chlorohexadecanoic acid in rats.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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