{"doi":"10.1042/bj2330589","title":"Binding of [14C]malonyl-CoA to rat liver mitochondria after blocking of the active site of carnitine palmitoyltransferase I. Displacement of low-affinity binding by palmitoyl-CoA","abstract":"<jats:p>The active site of the overt activity of carnitine palmitoyltransferase (CPT I) in rat liver mitochondria was blocked by the self-catalysed formation of the S-carboxypalmitoyl-CoA ester of (-)-carnitine, followed by washing of the mitochondria. CPT I activity in treated mitochondria was inhibited by 90-95%. Binding of [14C]malonyl-CoA to these mitochondria was not inhibited as compared with that of control mitochondria. When CPT I activity was inhibited, palmitoyl-CoA could markedly displace [14C]malonyl-CoA binding from the low-affinity site for the inhibitor [Zammit, Corstorphine &amp; Gray (1984) Biochem. J. 222, 335-342], but not from the high-affinity site for malonyl-CoA binding. The saturation characteristics of the malonyl-CoA-binding component lost in the presence of palmitoyl-CoA were sigmoidal, and thus suggestive of co-operative binding at this site. It is suggested that the site hitherto considered to be a low-affinity malonyl-CoA-binding site may be effectively a second, allosteric, acyl-CoA-binding site on CPT I under conditions that prevail in vivo, whereas the high-affinity site for malonyl-CoA may be exclusive to the inhibitor. The possibility that the competitive-type interactions of malonyl-CoA and acyl-CoA on CPT I activity could arise from the effects of separate malonyl-CoA and acyl-CoA allosteric sites is considered. The possible significance of the large difference in the capacity of the two sites and their different saturation kinetics is also discussed.</jats:p>","journal":"Biochemical Journal","year":1986,"id":686315,"datarank":0.4943755299006494,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.0,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"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":1793027,"name":"V A Zammit","orcid":null,"position":1,"is_corresponding":false},{"id":1793026,"name":"B D Grantham","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Binding of [14C]malonyl-CoA to rat liver mitochondria after blocking of the active site of carnitine palmitoyltransferase I. Displacement of low-affinity binding by palmitoyl-CoA","abstract":"<jats:p>The active site of the overt activity of carnitine palmitoyltransferase (CPT I) in rat liver mitochondria was blocked by the self-catalysed formation of the S-carboxypalmitoyl-CoA ester of (-)-carnitine, followed by washing of the mitochondria. CPT I activity in treated mitochondria was inhibited by 90-95%. Binding of [14C]malonyl-CoA to these mitochondria was not inhibited as compared with that of control mitochondria. When CPT I activity was inhibited, palmitoyl-CoA could markedly displace [14C]malonyl-CoA binding from the low-affinity site for the inhibitor [Zammit, Corstorphine &amp; Gray (1984) Biochem. J. 222, 335-342], but not from the high-affinity site for malonyl-CoA binding. The saturation characteristics of the malonyl-CoA-binding component lost in the presence of palmitoyl-CoA were sigmoidal, and thus suggestive of co-operative binding at this site. It is suggested that the site hitherto considered to be a low-affinity malonyl-CoA-binding site may be effectively a second, allosteric, acyl-CoA-binding site on CPT I under conditions that prevail in vivo, whereas the high-affinity site for malonyl-CoA may be exclusive to the inhibitor. The possibility that the competitive-type interactions of malonyl-CoA and acyl-CoA on CPT I activity could arise from the effects of separate malonyl-CoA and acyl-CoA allosteric sites is considered. The possible significance of the large difference in the capacity of the two sites and their different saturation kinetics is also discussed.</jats:p>","is_dataset_classified":null,"base_score":3.295836866004329,"endowment":3.295836866004329,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"3954755","pmcid":"PMC1153067","openalex_id":"https://openalex.org/W2335741288","authors":[],"funders":[],"total_grants":0,"fwci":4.5152,"citation_percentile":0.96103896,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://portlandpress.com/biochemj/article-pdf/233/2/589/586854/bj2330589.pdf","host_type":"journal"},{"url":"https://portlandpress.com/biochemj/article-pdf/233/2/589/586854/bj2330589.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj2330589","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/3954755","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1153067","host_type":"repository"}],"fields_of_study":["Metabolism and Genetic Disorders","Metabolomics and Mass Spectrometry Studies","Mitochondrial Function and Pathology","Acyl Coenzyme A","Acyltransferases","Animals","Binding Sites","Carnitine","Carnitine O-Palmitoyltransferase","Coenzyme A","Isoenzymes","Malonyl Coenzyme A","Mitochondria, Liver","Palmitoyl Coenzyme A","Rats"],"mesh_terms":["Acyl Coenzyme A","Acyltransferases","Animals","Binding Sites","Carnitine","Carnitine O-Palmitoyltransferase","Coenzyme A","Isoenzymes","Malonyl Coenzyme A","Mitochondria, Liver","Palmitoyl Coenzyme A","Rats"],"keywords":["Malonyl-CoA","Carnitine palmitoyltransferase I","Carnitine","Allosteric regulation","Carnitine O-palmitoyltransferase","Binding site","Mitochondrion","Biochemistry","Acyl-CoA","Chemistry","Biology","Enzyme","Beta oxidation"],"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":"2026-08-18T19:09:22.273804Z","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":[]}