Omega-oxidation of fatty acids studied in isolated liver cells.
The omega- and beta-oxidation of medium- and long-chain fatty acids (C10-C18) were studied in hepatocytes from fasted, fed and clofibrate-fed rats. The omega-oxidation systems were most active with lauric acid (12:0) and decanoic acid (10:0) as substrates and there was decreasing activity with chain lengths from 14 to 18 carbon atoms. In fed rats no omega-oxidation of fatty acids was detected unless the mitochondrial beta-oxidation was inhibited. In fasted rats the omega-oxidation was less than 2% and preincubation with (+)-decanoylcarnitine increased the omega-oxidation to 15% of the total fatty acid oxidation. Clofibrate feeding did not increase the omega-oxidation in isolated hepatocytes. Inhibition of the alcohol dehydrogenase with 4-methylpyrazole inhibited both the oxidation of omega-hydroxylated fatty acid and the initial hydroxylation of lauric acid to dicarboxylic acid, suggesting the importance of the alcohol dehydrogenase in the omega-oxidation of fatty acids. 95% of the dicarboxylic acids and 80% of the hydroxy-fatty acids were excreted from the cells in the incubations with decanoic acid (10:0). No chain-shortened dicarboxylic acids were detected with [1-14C]decanoic- or [1-14C]lauric acid as substrate, while small amounts C10 and C12 dicarboxylic acids were observed in incubations with [1-14C]myristic acid (14:0).
Christensen
E
E
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
Grønn
M
M
Hagve
T A
TA
Christophersen
B O
BO
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; C002893:decanoylcarnitine; D000426:Alcohol Dehydrogenase; D002331:Carnitine