{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:44:03Z","timestamp":1791888243959,"version":"4.3.4"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,8,15]]},"abstract":"<jats:p>The role of carbonic anhydrase in de novo lipid synthesis was examined by measuring [1-14C]acetate incorporation into total lipids, fatty acids and non-saponifiable lipids in freshly isolated rat hepatocytes. Two carbonic anhydrase inhibitors, trifluoromethylsulphonamide (TFMS) and ethoxozolamide (ETZ) decreased incorporation of 14C into total lipids. Both fatty acid and non-saponifiable lipid components of the total lipid were inhibited to approximately the same extent by 100 microM TFMS (29 +\/- 0.3% and 35 +\/- 0.3% of control respectively in replicate studies). However, neither drug significantly affected ATP concentrations or the transport activity of Na+\/K(+)-ATPase, two measures of cell viability. To establish the site of this inhibition, water-soluble 14C-labelled metabolites from perchloric acid extracts of the radiolabelled cells were separated by ion-exchange chromatography. TFMS inhibited 14C incorporation into citrate, malate, alpha-oxoglutarate and fumarate, but had no effect on incorporation of 14C into acetoacetate. Since ATP citrate-lyase, the cytosolic enzyme that catalyses the conversion of citrate into acetyl-CoA, catalyses an early rate-limiting step in fatty acid synthesis, levels of cytosolic citrate may be rate controlling for de novo fatty acid and sterol synthesis. Indeed citrate concentrations were significantly reduced to 37 +\/- 6% of control in hepatocytes incubated with 100 microM TFMS for 30 min. TFMS also inhibited the incorporation of 14C from [1-14C]pyruvate into malate, citrate and glutamate, but not into lactate. This supports the hypothesis that TFMS inhibits pyruvate carboxylation, i.e. since all of the 14C from [1-14C]pyruvate converted into citric acid cycle intermediates must come via pyruvate carboxylase (i.e. rather than pyruvate dehydrogenase). Our findings indicate a role for carbonic anhydrase in hepatic de novo lipogenesis at the level of pyruvate carboxylation.<\/jats:p>","DOI":"10.1042\/bj3100197","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:44:51Z","timestamp":1439243091000},"page":"197-202","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Role of hepatic carbonic anhydrase in <i>de novo<\/i> lipogenesis"],"prefix":"10.1042","volume":"310","author":[{"given":"C J","family":"Lynch","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Physiology, College of Medicine, The Milton S. Hershey Medical Center and Children's Hospital, The Pennsylvania State University, Hershey, PA 17033, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, College of Medicine, The Milton S. Hershey Medical Center and Children's Hospital, The Pennsylvania State University, Hershey, PA 17033, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S A","family":"Hazen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, College of Medicine, The Milton S. Hershey Medical Center and Children's Hospital, The Pennsylvania State University, Hershey, PA 17033, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B A","family":"Stanley","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, College of Medicine, The Milton S. Hershey Medical Center and Children's Hospital, The Pennsylvania State University, Hershey, PA 17033, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Dodgson","sequence":"additional","affiliation":[{"name":"Deparment of Physiology, University of Pennsylvania, School of Medicine,Philadelphia, PA 19104, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K F","family":"Lanoue","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, College of Medicine, The Milton S. Hershey Medical Center and Children's Hospital, The Pennsylvania State University, Hershey, PA 17033, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/310\/1\/197\/728473\/bj3100197.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/310\/1\/197\/728473\/bj3100197.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T23:50:51Z","timestamp":1637711451000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/310\/1\/197\/32311\/Role-of-hepatic-carbonic-anhydrase-in-de-novo"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,8,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,8,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3100197","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,8,15]]}}}