Coupling of ethanol metabolism to lipid biosynthesis: labelling of the glycerol moieties of sn-glycerol-3-phosphate, a phosphatidic acid and a phosphatidylcholine in liver of rats given [1,1-2H2]ethanol.
The mechanism behind ethanol-induced fatty liver was investigated by administration of [1,1-2H2]ethanol to rats and analysis of intermediates in lipid biosynthesis. Phosphatidic acid and phosphatidylcholine were isolated by chromatography on a lipophilic anion exchanger and molecular species were isolated by high-performance liquid chromatography in a non-aqueous system. The glycerol moieties of palmitoyl-linoleoylphosphatidic acid, the corresponding phosphatidylcholine and free sn-glycerol-3-phosphate were analysed by GC/MS of methyl ester t-butyldimethylsilyl derivatives. The deuterium labelling in the glycerol moiety of the phosphatidic acid was 2-3-times higher than in free sn-glycerol-3-phosphate, indicating that a specific pool of sn-glycerol-3-phosphate was used for the synthesis of phosphatidic acid in liver. The results indicate that NADH formed during ethanol oxidation is used in the formation of a pool of sn-glycerol-3-phosphate that gives rise to triacylglycerol and possibly fatty liver.
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Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Cronholm
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D000818:Animals; D003903:Deuterium; D000431:Ethanol / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000096:biosynthesis
D005994:Glycerophosphates; D008055:Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D014280:Triglycerides; D009243:NAD; D000431:Ethanol; C029620:alpha-glycerophosphoric acid; D003903:Deuterium; D005990:Glycerol