{"doi":"10.1002/hep.510270124","title":"Regulation of early cholesterol biosynthesis in rat liver: Effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities","abstract":"<jats:sec>\n            <jats:title/>\n            <jats:p>Cytosolic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase catalyzes the formation of HMG-CoA, the substrate for the rate-controlling enzyme in the cholesterol biosynthetic pathway. To explore the regulation in liver, we developed a new, accurate, and reliable reversed-phase ion-pair chromatographic assay that uses nonradioactive substrates and <jats:italic toggle=\"yes\">n</jats:italic>-propionyl coenzyme A as an internal recovery standard. The hepatic activities were measured in rats treated with cholesterol, sitosterol, cholic acid, deoxycholic acid, ursodeoxycholic acid, cholestyramine, bile fistula, lovastatin, and BM 15.766, an inhibitor of 7-dehydrocholesterol Δ<jats:sup>7</jats:sup>-reductase, and were compared with microsomal HMG-CoA reductase and cytosolic acetoacetyl coenzyme A (AcAc-CoA) thiolase activities. HMG-CoA synthase activity was effectively suppressed in synchrony with HMG-CoA reductase activity by treatments with cholesterol (−41%, <jats:italic toggle=\"yes\">P</jats:italic>&lt; .05), cholic acid (−72%, <jats:italic toggle=\"yes\">P</jats:italic>&lt; .005), and deoxycholic acid (−62%, <jats:italic toggle=\"yes\">P</jats:italic>&lt; .05). However, ursodeoxycholic acid increased activity 84% (<jats:italic toggle=\"yes\">P</jats:italic>&lt; .05) and intravenous sitosterol did not change activity. AcAc-CoA thiolase activities also paralleled HMG-CoA reductase and HMG-CoA synthase activities, but differences were not statistically significant. In contrast to inhibition, up-regulation of hepatic HMG-CoA synthase activities by cholestyramine, bile fistula, and lovastatin was much less than HMG-CoA reductase activities. In addition, BM 15.766 did not stimulate synthase activity, whereas lovastatin increased activity 2.4-fold. Thus, hepatic HMG-CoA synthase activity was regulated coordinately with HMG-CoA reductase, and responded more forcefully to regulatory stimuli than acetoacetyl-CoA thiolase activity but usually less than HMG-CoA reductase.</jats:p>\n          </jats:sec>","journal":"Hepatology","year":1998,"id":22037,"datarank":1.2065194679305091,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.7571596268974106,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.7571596268974106,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":18,"citers_with_citation_signal":15,"citers_with_endowment":15,"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":139869,"name":"Gerald Salen","orcid":null,"position":1,"is_corresponding":false},{"id":139870,"name":"Lien B. Nguyen","orcid":null,"position":2,"is_corresponding":false},{"id":139871,"name":"Guorong Xu","orcid":null,"position":3,"is_corresponding":false},{"id":139872,"name":"Stephen G. Tint","orcid":null,"position":4,"is_corresponding":false},{"id":139873,"name":"Ashok K. Batta","orcid":null,"position":5,"is_corresponding":false},{"id":139874,"name":"Sarah Shefer","orcid":null,"position":6,"is_corresponding":false},{"id":139868,"name":"Akira Honda","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9425931","pmcid":null,"openalex_id":"https://openalex.org/W2044594614","authors":[],"funders":[{"funder_name":"NICHD NIH HHS","grant_id":"HD-31932","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL-17818","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK 26756","title":null}],"total_grants":3,"fwci":0.3617,"citation_percentile":0.57884106,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2014,"count":3},{"year":2016,"count":1},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2025,"count":1}],"oa_status":"bronze","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.510270124","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.510270124","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.510270124","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fhep.510270124","host_type":"publisher"},{"url":"https://journals.lww.com/01515467-199801000-00024","host_type":"publisher"},{"url":"https://doi.org/10.1002/hep.510270124","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9425931","host_type":"repository"}],"fields_of_study":["Plant biochemistry and biosynthesis","Cholesterol and Lipid Metabolism","Computational Drug Discovery Methods","Medicine","Biology","Chemistry","Acetyl-CoA C-Acetyltransferase","Animals","Anticholesteremic Agents","Bile Acids and Salts","Cholesterol","Cholestyramine Resin","Hydroxymethylglutaryl-CoA Synthase","Liver","Lovastatin","Male","Piperazines","Rats","Rats, Sprague-Dawley","Sterols"],"mesh_terms":["Acetyl-CoA C-Acetyltransferase","Animals","Anticholesteremic Agents","Bile Acids and Salts","Cholesterol","Cholestyramine Resin","Hydroxymethylglutaryl-CoA Synthase","Liver","Lovastatin","Male","Piperazines","Sterols","Rats, Sprague-Dawley","Rats"],"keywords":["Thiolase","Lovastatin","Reductase","HMG-CoA reductase","Coenzyme A","Biochemistry","Mevalonic acid","Hydroxymethylglutaryl-CoA reductase","Cholestyramine","CYP8B1","Cholic acid","Bile acid","Cholesterol","7-Dehydrocholesterol reductase","Biology","Chemistry","Enzyme","Internal medicine","Medicine"],"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":"2026-06-06T17:42:02.762293Z","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":[]}