Changes of fatty acid composition of phospholipids and lipid structural order in rat liver mitochondrial membrane subsequent to galactosamine intoxication. Effect of clofibrate.
Since it has been earlier reported that D-galactosamine induces an inhibition of palmitoylcarnitine transferase I and a depletion of mitochondrial phospholipids which were both prevented by clofibrate, an evaluation of the effects of these drugs on mitochondrial fatty acid composition was made. Galactosamine does not alter the fatty acid pattern of these fatty acids whereas clofibrate induces a 2-fold increase in monounsaturated/saturated fatty acids ratio and a 10-fold decrease of the 20:4 (n - 6)/20:3 (n - 6) ratio in phosphatidylcholine. These alterations suggest an increase of delta 9-desaturation and a decrease of delta 5-desaturation. To determine whether the drug-induced changes in mitochondrial phospholipids has an effect on the physical properties of the membrane, the lipid structural order of mitochondrial preparations was studied using the lipophilic probes DPH and TMA-DPH. Mitochondrial isolated either from galactosamine- or clofibrate-treated rats showed a decrease in fluorescence polarization, indicating an overall decrease in lipid structural order. This alteration is more drastic when both drugs are administered. This phenomenon suggests drastic changes in the bulk phase of inner mitochondrial membrane lipids after treatments and could explain the altered kinetic properties of palmitoylcarnitine transferase I.
D000818:Animals; D002308:Cardiolipins / Q000502:physiology; D002994:Clofibrate / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005454:Fluorescence Polarization; D005688:Galactosamine / Q000633:toxicity*; D007425:Intracellular Membranes / Q000187:drug effects; D008297:Male; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D002308:Cardiolipins; D005227:Fatty Acids; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D005688:Galactosamine; D002994:Clofibrate