title: Ethionine-induced alterations of enzymes involved in lipid metabolism and their possible relationship to induction of fatty liver.
abstract: Changes of enzymes involved in the hepatic metabolism of long-chain fatty acids (palmitoyl-CoA synthetase (EC 6.2.1.3), carnitine palmitoyltransferase (EC 6.2.1.3), glycerophosphate acyltransferase (EC 2.3.1.15)) in the liver of male rats were examined after ethionine exposure. Ethionine administration resulted in a dose- and time-dependent enhancement of the palmitoyl-CoA synthetase activity both in the mitochondrial, peroxisomal and microsomal fractions. The total carnitine palmitoyltransferase activity in the mitochondrial fraction was enhanced. Ethionine administration was also associated with dose- and time-dependent changes of the microsomal glycerophosphate acyltransferase activity, whereas the mitochondrial enzyme activity was marginally affected. The hepatic triacylglycerol content of the ethionine-treated animals was increased. Hepatic lipids were accumulated in large droplets. Serum triacylglycerol and cholesterol were decreased. In particular, the serum HDL-cholesterol level was lowered. The concentration of ATP in the liver decreased. Accumulation of the metabolic product S-adenosylethionine (AdoEth) was observed for the first 2 days of exposure followed by a fall in S-adenosylmethionine (Ado-Met) during the next 10 days. Linear regression analysis of ATP content versus AdoEth and AdoMet showed highly significant correlations. A significant correlation between the hepatic triacylglycerol and AdoEth content was also observed upon ethionine treatment. The data show that ethionine perturbs the hepatic lipid metabolism. Enhanced esterification of long-chain fatty acids, but not a simple reduction of their oxidation, might contribute to ethionine-induced fatty liver in addition to a block in secretion of lipoproteins and decreased protein synthesis.
authors.affiliation: Laboratory of Clinical Biochemistry, University of Bergen, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Aarsaether
authors.forename: R K
authors.initials: RK
authors.lastname: Berge
authors.forename: A M
authors.initials: AM
authors.lastname: Husøy
authors.forename: A
authors.initials: A
authors.lastname: Aarsland
authors.forename: H
authors.initials: H
authors.lastname: Kryvi
authors.forename: A
authors.initials: A
authors.lastname: Svardal
authors.forename: P M
authors.initials: PM
authors.lastname: Ueland
authors.forename: M
authors.initials: M
authors.lastname: Farstad
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000378:metabolism*; D005001:Ethionine / Q000494:pharmacology*; D005234:Fatty Liver / Q000209:etiology*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000217:Acyltransferases; D005992:Glycerol-3-Phosphate O-Acyltransferase; D002334:Carnitine O-Palmitoyltransferase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D005001:Ethionine