A role for 2,4-enoyl-CoA reductase in mitochondrial beta-oxidation of polyunsaturated fatty acids. Effects of treatment with clofibrate on oxidation of polyunsaturated acylcarnitines by isolated rat liver mitochondria.
1. beta-Oxidation of gamma-linolenoylcarnitine, arachidonoylcarnitine and docosahexaenoylcarnitine by isolated rat liver mitochondria is inhibited by uncoupling conditions. Partial re-activation is obtained with added ATP. With mitochondria from clofibrate-treated rats ATP-stimulated rates of beta-oxidation of docosahexaenoylcarnitine are higher than ADP-stimulated rates. This is not observed with the beta-oxidation of oleoylcarnitine. 2. beta-Oxidation of docosahexaenoylcarnitine, in the presence of rotenone, is inhibited by added oxaloacetate, analogous to previous findings with pent-4-enoylcarnitine [see Osmundsen (1978) FEBS Lett. 88, 219-222]. In the absence of rotenone added oxaloacetate stimulates the beta-oxidation of docosahexaenoylcarnitine, but has the opposite effect on the beta-oxidation of palmitoylcarnitine. 3. beta-Oxidation of polyunsaturated acylcarnitines by isolated rat liver mitochondria is selectively increased after treatment of the animals with a low dietary dose (0.2%, w/w) of clofibrate. Treatment with a higher dose of clofibrate (0.5%, w/w) resulted in a general stimulation of beta-oxidation. 4. The results presented suggest that long-chain fatty acids possessing a delta 4-double bond are not readily beta-oxidized unless the 2,4-enoyl-CoA reductase (EC 1.3.1.-) is operating.
D019297:2,4-Dinitrophenol; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D004140:Dinitrophenols; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D010071:Oxaloacetates / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D004140:Dinitrophenols; D010071:Oxaloacetates; D014475:Uncoupling Agents; D012402:Rotenone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D044943:Fatty Acid Desaturases; D002994:Clofibrate; D019297:2,4-Dinitrophenol; D002331:Carnitine