{"doi":"10.1042/bj1290055","title":"Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its co-enzyme A and carnitine esters","abstract":"<jats:p>1. The CoA and carnitine esters of 2-bromopalmitate are extremely powerful and specific inhibitors of mitochondrial fatty acid oxidation. 2. 2-Bromopalmitoyl-CoA, added as such or formed from 2-bromopalmitate, inhibits the carnitine-dependent oxidation of palmitate or palmitoyl-CoA, but not the oxidation of palmitoylcarnitine, by intact liver mitochondria. 3. 2-Bromopalmitoylcarnitine inhibits the oxidation of palmitoylcarnitine as well as that of palmitate or palmitoyl-CoA. It has no effect on succinate oxidation, but inhibits that of pyruvate, 2-oxoglutarate or hexanoate; however, the oxidation of these substrates (but not of palmitate, palmitoyl-CoA or palmitoyl-carnitine) is restored by carnitine. 4. In damaged mitochondria, added 2-bromopalmitoyl-CoA does inhibit palmitoylcarnitine oxidation; pyruvate oxidation is unaffected by the inhibitor alone, but is impaired if palmitoylcarnitine is subsequently added. 5. The findings have been interpreted as follows. 2-Bromopalmitoyl-CoA inactivates (in a carnitine-dependent manner) a pool of carnitine palmitoyltransferase which is accessible to external acyl-CoA. This results in inhibition of palmitate or palmitoyl-CoA oxidation. A second pool of carnitine palmitoyltransferase, inaccessible to added acyl-CoA in intact mitochondria, can generate bromopalmitoyl-CoA within the matrix from external 2-bromopalmitoylcarnitine; this reaction is reversible. Such internal 2-bromopalmitoyl-CoA inactivates long-chain β-oxidation (as does added 2-bromopalmitoyl-CoA if the mitochondria are damaged) and its formation also sequesters intramitochondrial CoA. Since this CoA is shared by pyruvate and 2-oxoglutarate dehydrogenases, the oxidation of their substrates is depressed by 2-bromopalmitoylcarnitine, unless free carnitine is available to act as a ‘sink’ for long-chain acyl groups. 6. These effects are compared with those reported for other inhibitors of fatty acid oxidation.</jats:p>","journal":"Biochemical Journal","year":1972,"id":626750,"datarank":0.7755725992557229,"base_score":5.170483995038151,"endowment":5.170483995038151,"self_citation_contribution":0.7755725992557229,"citation_network_contribution":0.0,"self_endowment_contribution":0.7755725992557229,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":175,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":117818,"name":"P. K. Tubbs","orcid":null,"position":1,"is_corresponding":false},{"id":1621378,"name":"J. F. A. Chase","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its co-enzyme A and carnitine esters","abstract":"<jats:p>1. The CoA and carnitine esters of 2-bromopalmitate are extremely powerful and specific inhibitors of mitochondrial fatty acid oxidation. 2. 2-Bromopalmitoyl-CoA, added as such or formed from 2-bromopalmitate, inhibits the carnitine-dependent oxidation of palmitate or palmitoyl-CoA, but not the oxidation of palmitoylcarnitine, by intact liver mitochondria. 3. 2-Bromopalmitoylcarnitine inhibits the oxidation of palmitoylcarnitine as well as that of palmitate or palmitoyl-CoA. It has no effect on succinate oxidation, but inhibits that of pyruvate, 2-oxoglutarate or hexanoate; however, the oxidation of these substrates (but not of palmitate, palmitoyl-CoA or palmitoyl-carnitine) is restored by carnitine. 4. In damaged mitochondria, added 2-bromopalmitoyl-CoA does inhibit palmitoylcarnitine oxidation; pyruvate oxidation is unaffected by the inhibitor alone, but is impaired if palmitoylcarnitine is subsequently added. 5. The findings have been interpreted as follows. 2-Bromopalmitoyl-CoA inactivates (in a carnitine-dependent manner) a pool of carnitine palmitoyltransferase which is accessible to external acyl-CoA. This results in inhibition of palmitate or palmitoyl-CoA oxidation. A second pool of carnitine palmitoyltransferase, inaccessible to added acyl-CoA in intact mitochondria, can generate bromopalmitoyl-CoA within the matrix from external 2-bromopalmitoylcarnitine; this reaction is reversible. Such internal 2-bromopalmitoyl-CoA inactivates long-chain β-oxidation (as does added 2-bromopalmitoyl-CoA if the mitochondria are damaged) and its formation also sequesters intramitochondrial CoA. Since this CoA is shared by pyruvate and 2-oxoglutarate dehydrogenases, the oxidation of their substrates is depressed by 2-bromopalmitoylcarnitine, unless free carnitine is available to act as a ‘sink’ for long-chain acyl groups. 6. These effects are compared with those reported for other inhibitors of fatty acid oxidation.</jats:p>","is_dataset_classified":null,"base_score":5.170483995038151,"endowment":5.170483995038151,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"4646779","pmcid":null,"openalex_id":"https://openalex.org/W43695440","authors":[],"funders":[],"total_grants":0,"fwci":7.6135,"citation_percentile":0.9748142,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":3},{"year":2014,"count":4},{"year":2015,"count":1},{"year":2016,"count":3},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":6},{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://portlandpress.com/biochemj/article-pdf/129/1/55/778156/bj1290055.pdf","host_type":"journal"},{"url":"https://portlandpress.com/biochemj/article-pdf/129/1/55/778156/bj1290055.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj1290055","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/4646779","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1174041","host_type":"repository"}],"fields_of_study":["Metabolism and Genetic Disorders","Mitochondrial Function and Pathology","Alcoholism and Thiamine Deficiency","Acetyltransferases","Animals","Carnitine","Coenzyme A","Esters","Fatty Acids","In Vitro Techniques","Male","Mitochondria, Liver","Oxidation-Reduction","Oxygen Consumption","Palmitic Acids","Pyruvates","Rats","Succinates"],"mesh_terms":["Acetyltransferases","Animals","Carnitine","Coenzyme A","Esters","Fatty Acids","Male","Mitochondria, Liver","Oxidation-Reduction","Oxygen Consumption","Palmitic Acids","Pyruvates","Succinates","Rats","In Vitro Techniques"],"keywords":["Palmitoylcarnitine","Carnitine","Beta oxidation","Mitochondrion","Coenzyme A","Biochemistry","Mitochondrial matrix","Carnitine O-palmitoyltransferase","Carnitine palmitoyltransferase I","Chemistry","Acyl-CoA","Enzyme","Biology","Cytosol"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T15:07:00.388777Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}