{"doi":"10.1042/bj2190601","title":"Effects of pH on the interaction of substrates and malonyl-CoA with mitochondrial carnitine palmitoyltransferase I","abstract":"<jats:p>The kinetics of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) were examined in mitochondria from rat liver, heart and skeletal muscle as a function of pH over the range 6.8-7.6. In all three tissues raising the pH resulted in a fall in the Km for carnitine, no change in the Km for palmitoyl-CoA or Octanoyl-CoA, and a marked decrease in the inhibitory potency of malonyl-CoA. Studies with skeletal-muscle mitochondria established that increasing pH was accompanied by an increase in the Kd of the malonyl-CoA binding site for this ligand, coupled with a decrease in the Kd for fatty acyl-CoA species to compete for malonyl-CoA binding. Three principal conclusions are drawn. (1) The pH-induced shift in malonyl-CoA sensitivity of CPT I is not a phenomenon restricted to liver mitochondria. (2) At any given pH within the range tested, the ability of malonyl-CoA (and closely related compounds) to inhibit enzyme activity is governed by the efficiency of their binding to the malonyl-CoA site. (3) The competitive interaction between fatty acyl-CoA substrates and malonyl-CoA as regards CPT I activity is exerted at the malonyl-CoA binding site. Finally, the possibility is strengthened that the malonyl-CoA binding site is distinct from the active site of CPT I.</jats:p>","journal":"Biochemical Journal","year":1984,"id":671055,"datarank":5.707331751831802,"base_score":4.356708826689592,"endowment":4.356708826689592,"self_citation_contribution":0.6535063240034389,"citation_network_contribution":5.053825427828363,"self_endowment_contribution":0.6535063240034389,"citer_contribution":5.053825427828363,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":69,"citers_with_citation_signal":63,"citers_with_endowment":63,"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":1753010,"name":"D W Foster","orcid":null,"position":1,"is_corresponding":false},{"id":1753011,"name":"J D McGarry","orcid":null,"position":2,"is_corresponding":false},{"id":1753009,"name":"S E Mills","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Effects of pH on the interaction of substrates and malonyl-CoA with mitochondrial carnitine palmitoyltransferase I","abstract":"<jats:p>The kinetics of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) were examined in mitochondria from rat liver, heart and skeletal muscle as a function of pH over the range 6.8-7.6. In all three tissues raising the pH resulted in a fall in the Km for carnitine, no change in the Km for palmitoyl-CoA or Octanoyl-CoA, and a marked decrease in the inhibitory potency of malonyl-CoA. Studies with skeletal-muscle mitochondria established that increasing pH was accompanied by an increase in the Kd of the malonyl-CoA binding site for this ligand, coupled with a decrease in the Kd for fatty acyl-CoA species to compete for malonyl-CoA binding. Three principal conclusions are drawn. (1) The pH-induced shift in malonyl-CoA sensitivity of CPT I is not a phenomenon restricted to liver mitochondria. (2) At any given pH within the range tested, the ability of malonyl-CoA (and closely related compounds) to inhibit enzyme activity is governed by the efficiency of their binding to the malonyl-CoA site. (3) The competitive interaction between fatty acyl-CoA substrates and malonyl-CoA as regards CPT I activity is exerted at the malonyl-CoA binding site. Finally, the possibility is strengthened that the malonyl-CoA binding site is distinct from the active site of CPT I.</jats:p>","is_dataset_classified":null,"base_score":4.356708826689592,"endowment":4.356708826689592,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"6743235","pmcid":"PMC1153518","openalex_id":"https://openalex.org/W2404646134","authors":[],"funders":[{"funder_name":"NIADDK NIH HHS","grant_id":"AM 07139","title":null},{"funder_name":"NIADDK NIH HHS","grant_id":"AM 07307","title":null},{"funder_name":"NIADDK NIH HHS","grant_id":"AM 18573","title":null}],"total_grants":3,"fwci":6.3317,"citation_percentile":0.97276917,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2020,"count":1},{"year":2023,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1153518","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1153518","host_type":"repository"},{"url":"https://portlandpress.com/biochemj/article-pdf/219/2/601/581561/bj2190601.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj2190601","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/6743235","host_type":"repository"}],"fields_of_study":["Metabolism and Genetic Disorders","Peroxisome Proliferator-Activated Receptors","Mitochondrial Function and Pathology","Acyl Coenzyme A","Acyltransferases","Animals","Binding Sites","Carnitine O-Palmitoyltransferase","Hydrogen-Ion Concentration","In Vitro Techniques","Kinetics","Malonyl Coenzyme A","Mitochondria","Mitochondria, Heart","Mitochondria, Liver","Mitochondria, Muscle","Rats","Rats, Inbred Strains"],"mesh_terms":["Acyl Coenzyme A","Acyltransferases","Animals","Binding Sites","Carnitine O-Palmitoyltransferase","Hydrogen-Ion Concentration","Kinetics","Malonyl Coenzyme A","Mitochondria","Mitochondria, Heart","Mitochondria, Liver","Mitochondria, Muscle","Rats, Inbred Strains","Rats","In Vitro Techniques"],"keywords":["Malonyl-CoA","Carnitine O-palmitoyltransferase","Carnitine palmitoyltransferase I","Carnitine","Biochemistry","Chemistry","Mitochondrion","Binding site","Skeletal muscle","Acyl-CoA","Beta oxidation","Enzyme","Biology","Endocrinology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T01:09:53.670166Z","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":[]}