{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:12:33Z","timestamp":1758402753792,"version":"3.30.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8005,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Increased esterification of fatty acids to triglyceride is common to most of the mechanisms proposed to explain the causation of alcoholic fatty liver. However, it is unclear whether this is caused by increased substrate supply or whether direct stimulation of the enzymes of the esterification pathway occurs after excessive alcohol intake. The rate-limiting step in triglyceride synthesis is catalyzed by the enzyme phosphatidate phosphohydrolase, which is present in the cytosol and microsomes and is sensitive to inhibition by N-ethylmaleimide. This enzyme is physically distinct from a second form of phosphatidate phosphohydrolase that is located predominantly in the plasma membrane, is insensitive to N-ethylmaleimide inhibition and has a putative role in cell-signaling. We have investigated whether the activity of the N-ethylmaleimide-sensitive (\u201cmetabolic\u201d) form of phosphatidate phosphohydrolase is increased in patients with alcoholic liver disease and whether any increased activity correlates with the severity of steatosis. N-ethylmaleimide-sensitive and -insensitive phosphatidate phosphohydrolase activities were measured in needle liver biopsy specimens from 42 alcoholic patients and 6 patients with primary biliary cirrhosis and in wedge biopsy specimens from 6 normal patients undergoing routine cholecystectomy. Steatosis was \u201cscored\u201d on coded slides from 0 to 3. N-ethylmaleimide-sensitive activity was higher in alcoholic biopsy specimens scoring 3 (3.25 \u00b1 0.4 units\/mg protein, n = 10) than in those scoring either 0 (1.21 \u00b1 0.2, n = 14) or 1 to 2 (1.58 \u00b1 0.2, n = 18), and it was also higher than in biopsy specimens from normal and primary biliary cirrhosis patients (1.65 \u00b1 0.3, n = 12; p &lt; 0.0001, analysis of variance). No differences were found in age, weight, cumulative or current alcohol intake, coexistent cirrhosis or N-ethylmaleimide-insensitive activity between the groups of alcoholic patients with different fat scores. These results demonstrate that the activity of metabolic, N-ethylmaleimide-sensitive phosphatidate phosphohydrolase is increased in some patients with alcoholic liver disease. That this increase was only observed in patients with severe alcoholic steatosis suggests that the activity of this enzyme may play a role in the pathogenesis of alcoholic fatty liver and may, in part, explain differences in susceptibility to this common complication of alcohol abuse. (HEPATOLOGY 1993;18:832-838).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840180413","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T02:07:39Z","timestamp":1172974059000},"page":"832-838","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["The activity of the metabolic form of hepatic phosphatidate phosphohydrolase correlates with the severity of alcoholic fatty liver in human beings"],"prefix":"10.1097","volume":"18","author":[{"given":"Christopher P.","family":"Day","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver F. W.","family":"James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley J. M.","family":"St. Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark K.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian N.","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Yeaman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840180413-BIB1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00005792-196703000-00006","volume":"46","author":"Edmondson","year":"1967","journal-title":"Medicine"},{"key":"10.1002\/hep.1840180413-BIB2","first-page":"232","volume":"52","author":"Hislop","year":"1983","journal-title":"Q J Med"},{"key":"10.1002\/hep.1840180413-BIB3","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1136\/bmj.1.6075.1497","volume":"1","author":"Krasner","year":"1977","journal-title":"Br Med J"},{"key":"10.1002\/hep.1840180413-BIB4","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1136\/bmj.1.6066.939","volume":"1","author":"Morgan","year":"1977","journal-title":"Br Med J"},{"key":"10.1002\/hep.1840180413-BIB5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1136\/gut.15.1.52","volume":"15","author":"Brunt","year":"1974","journal-title":"Gut"},{"key":"10.1002\/hep.1840180413-BIB6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0140-6736(84)90295-2","volume":"2","author":"Sorenson","year":"1984","journal-title":"Lancet"},{"key":"10.1002\/hep.1840180413-BIB7","first-page":"633","volume":"30","author":"Durlacher","year":"1954","journal-title":"Am J Pathol"},{"key":"10.1002\/hep.1840180413-BIB8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3109\/00365527809179824","volume":"13","author":"Morgan","year":"1978","journal-title":"Scand J Gastroenterol"},{"key":"10.1002\/hep.1840180413-BIB9","first-page":"16","volume":"74","author":"Graham","year":"1944","journal-title":"Bull Johns Hopkins Hosp"},{"key":"10.1002\/hep.1840180413-BIB10","first-page":"64","volume-title":"Principles and practice of medicine","author":"Osler","year":"1892","unstructured":"Principles and practice of medicine. New York: D Appleton and Company, 1892: 64."},{"key":"10.1002\/hep.1840180413-BIB11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF02532134","volume":"9","author":"Lieber","year":"1974","journal-title":"Lipids"},{"key":"10.1002\/hep.1840180413-BIB12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/hep.1840010106","volume":"1","author":"Salaspuro","year":"1981","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.1840180413-BIB13","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1042\/bj2320877","volume":"232","author":"Ryle","year":"1985","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1042\/bst0160251","volume":"16","author":"Brindley","year":"1988","journal-title":"Biochem Soc Trans"},{"key":"10.1002\/hep.1840180413-BIB15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/00005792-196209000-00003","volume":"41","author":"Leevy","year":"1962","journal-title":"Medicine"},{"key":"10.1002\/hep.1840180413-BIB16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0168-8278(90)90151-G","volume":"10","author":"Derr","year":"1990","journal-title":"J Hepatol"},{"key":"10.1002\/hep.1840180413-BIB17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1042\/cs0710253","volume":"71","author":"Leung","year":"1986","journal-title":"Clin Sci"},{"key":"10.1002\/hep.1840180413-BIB18","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1172\/JCI104266","volume":"40","author":"Lieber","year":"1961","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840180413-BIB19","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1042\/bj2280673","volume":"228","author":"Grunnet","year":"1985","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0163-7827(84)90001-8","volume":"23","author":"Brindley","year":"1984","journal-title":"Prog Lipid Res"},{"key":"10.1002\/hep.1840180413-BIB21","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0022-2275(20)37745-2","volume":"25","author":"Savolainen","year":"1984","journal-title":"J Lipid Res"},{"key":"10.1002\/hep.1840180413-BIB22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1172\/JCI109268","volume":"63","author":"Lamb","year":"1979","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840180413-BIB23","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1042\/bst0171115","volume":"17","author":"Simpson","year":"1989","journal-title":"Biochem Soc Trans"},{"key":"10.1002\/hep.1840180413-BIB24","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/0006-291X(77)91071-3","volume":"75","author":"Savolainen","year":"1977","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/hep.1840180413-BIB25","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1042\/bj1660639","volume":"166","author":"Pritchard","year":"1977","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB26","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1016\/S0021-9258(18)49945-0","volume":"266","author":"Jamal","year":"1991","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840180413-BIB27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0005-2760(92)90205-A","volume":"1127","author":"Day","year":"1992","journal-title":"Biochim Biophys Acta"},{"key":"10.1002\/hep.1840180413-BIB28","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/0014-5793(84)80752-8","volume":"175","author":"Martin-Sanz","year":"1984","journal-title":"FEBS Lett"},{"key":"10.1002\/hep.1840180413-BIB29","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/hep.1840140509","volume":"14","author":"Day","year":"1991","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.1840180413-BIB30","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1042\/bj2300525","volume":"230","author":"Pittner","year":"1985","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1365-2362.1984.tb01129.x","volume":"14","author":"Bj\u00f6rkhem","year":"1985","journal-title":"Eur J Clin Invest"},{"key":"10.1002\/hep.1840180413-BIB32","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/bj1460625","volume":"146","author":"Newby","year":"1975","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1042\/bj1860059","volume":"186","author":"Stanley","year":"1980","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0092-8674(82)90375-0","volume":"28","author":"Widnell","year":"1982","journal-title":"Cell"},{"key":"10.1002\/hep.1840180413-BIB35","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1093\/cvr\/18.6.384","volume":"18","author":"Hearse","year":"1984","journal-title":"Cardiovasc Res"},{"key":"10.1002\/hep.1840180413-BIB36","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1016\/S0021-9258(19)84554-4","volume":"261","author":"Walsh","year":"1986","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840180413-BIB37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1042\/bj1710263","volume":"171","author":"Sturton","year":"1978","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB38","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/0003-2697(81)90073-7","volume":"113","author":"Jensen","year":"1981","journal-title":"Anal Biochem"},{"key":"10.1002\/hep.1840180413-BIB39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1042\/bj2290343","volume":"229","author":"Belcher","year":"1985","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB40","doi-asserted-by":"crossref","first-page":"13367","DOI":"10.1016\/S0021-9258(18)33457-4","volume":"257","author":"Hostetler","year":"1982","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840180413-BIB41","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1016\/0006-2952(87)90512-0","volume":"36","author":"Chang","year":"1987","journal-title":"Biochem Pharmacol"},{"key":"10.1002\/hep.1840180413-BIB42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0003-9861(89)90268-3","volume":"271","author":"Ide","year":"1989","journal-title":"Arch Biochem Biophys"},{"key":"10.1002\/hep.1840180413-BIB43","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1055\/s-0028-1095714","volume":"6","author":"Tiengo","year":"1974","journal-title":"Horm Metab Res"},{"key":"10.1002\/hep.1840180413-BIB44","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1042\/bj2250455","volume":"225","author":"Pittner","year":"1985","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB45","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1042\/bj2400253","volume":"240","author":"Pittner","year":"1986","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB46","first-page":"420","volume":"37","author":"Wood","year":"1978","journal-title":"Fed Proc"},{"key":"10.1002\/hep.1840180413-BIB47","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1042\/bj1760885","volume":"176","author":"Savolainen","year":"1978","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB48","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/0005-2760(83)90059-0","volume":"753","author":"Lamb","year":"1983","journal-title":"Biochim Biophys Acta"},{"key":"10.1002\/hep.1840180413-BIB49","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1042\/bj1680147","volume":"168","author":"Whiting","year":"1977","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840180413-BIB50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1042\/bst0050037","volume":"5","author":"Fallon","year":"1977","journal-title":"Biochem Soc Trans"},{"key":"10.1002\/hep.1840180413-BIB51","first-page":"3","volume":"10","author":"Van Thiel","year":"1985","journal-title":"Current Concepts in Gastroenterology"},{"key":"10.1002\/hep.1840180413-BIB52","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1007\/BF01070758","volume":"20","author":"Hoyumpa","year":"1975","journal-title":"Dig Dis Sci"},{"key":"10.1002\/hep.1840180413-BIB53","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/hep.1840140509","volume":"14","author":"Day","year":"1991","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.1840180413-BIB54","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM198812223192505","volume":"319","author":"Lieber","year":"1988","journal-title":"N Engl J Med"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.1840180413","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199310000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:07:43Z","timestamp":1733051263000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199310000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,10]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1993]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.1840180413","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[1993,10]]}}}