{"doi":"10.1042/bj2450205","title":"Different sites of inhibition of carnitine palmitoyltransferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle","abstract":"<jats:p>The inhibition of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) by malonyl-CoA, acetyl-CoA and free CoA was studied in sonicated skeletal-muscle homogenates from normal human subjects and from five patients with a mutant CPT [Zierz &amp; Engel (1985) Eur. J. Biochem. 149, 207-214]. (1) Malonyl-CoA, acetyl-CoA and CoA were competitive inhibitors of CPT with palmitoyl-CoA. (2) Acetyl-CoA and CoA inhibited normal and mutant CPT to the same degree, whereas malonyl-CoA inhibited mutant CPT more than normal CPT. (3) Triton X-100 abolished the inhibition of normal CPT by malonyl-CoA, but not by acetyl-CoA or CoA. Triton X-100 by itself caused loss of activity of the mutant CPT. (4) In the concentration range 0.1-0.4 mM, the inhibitory effects of any two of the three inhibitors were synergistic. (5) The inhibitory constants (Ki) for acetyl-CoA and CoA were close to 45 microM. The Ki for malonyl-CoA was 200-fold lower, or 0.22 microM. Addition of 40 microM-acetyl-CoA or CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. Addition of 20 microM-CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. (6) The findings indicate that acetyl-CoA and CoA can inhibit CPT at the catalytic site or a nearby site which is different from that at which malonyl-CoA inhibits CPT. (7) The fact that small changes in the concentration of acetyl-CoA and CoA can antagonize the inhibitory effect of malonyl-CoA suggests that these compounds could modulate the inhibition of CPT by malonyl-CoA.</jats:p>","journal":"Biochemical Journal","year":1987,"id":688015,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":8,"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":1797388,"name":"A G Engel","orcid":null,"position":1,"is_corresponding":false},{"id":1587053,"name":"S Zierz","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Different sites of inhibition of carnitine palmitoyltransferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle","abstract":"<jats:p>The inhibition of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) by malonyl-CoA, acetyl-CoA and free CoA was studied in sonicated skeletal-muscle homogenates from normal human subjects and from five patients with a mutant CPT [Zierz &amp; Engel (1985) Eur. J. Biochem. 149, 207-214]. (1) Malonyl-CoA, acetyl-CoA and CoA were competitive inhibitors of CPT with palmitoyl-CoA. (2) Acetyl-CoA and CoA inhibited normal and mutant CPT to the same degree, whereas malonyl-CoA inhibited mutant CPT more than normal CPT. (3) Triton X-100 abolished the inhibition of normal CPT by malonyl-CoA, but not by acetyl-CoA or CoA. Triton X-100 by itself caused loss of activity of the mutant CPT. (4) In the concentration range 0.1-0.4 mM, the inhibitory effects of any two of the three inhibitors were synergistic. (5) The inhibitory constants (Ki) for acetyl-CoA and CoA were close to 45 microM. The Ki for malonyl-CoA was 200-fold lower, or 0.22 microM. Addition of 40 microM-acetyl-CoA or CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. Addition of 20 microM-CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. (6) The findings indicate that acetyl-CoA and CoA can inhibit CPT at the catalytic site or a nearby site which is different from that at which malonyl-CoA inhibits CPT. (7) The fact that small changes in the concentration of acetyl-CoA and CoA can antagonize the inhibitory effect of malonyl-CoA suggests that these compounds could modulate the inhibition of CPT by malonyl-CoA.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":8,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"3663146","pmcid":"PMC1148100","openalex_id":null,"authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"NS-6277","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://portlandpress.com/biochemj/article-pdf/245/1/205/591204/bj2450205.pdf","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1148100","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Muscles","Humans","Polyethylene Glycols","Octoxynol","Coenzyme A","Acyl Coenzyme A","Acetyl Coenzyme A","Malonyl Coenzyme A","Acyltransferases","Carnitine O-Palmitoyltransferase","Binding Sites","In Vitro Techniques"],"keywords":[],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.15086044.v1","title":"Additional file 1 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086044","title":"Additional file 1 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086047.v1","title":"Additional file 2 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086047","title":"Additional file 2 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086059.v1","title":"Additional file 6 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086059","title":"Additional file 6 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086068.v1","title":"Additional file 9 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15086068","title":"Additional file 9 of Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-19T12:12:30.071098Z","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":[]}