Regulation of linoleic acid delta 6-desaturation by a cytosolic lipoprotein-like fraction in isolated rat liver microsomes.
A peripheral component of the delta 6-fatty acid-desaturase system of rat liver microsomes has been isolated from the cytosol by ultracentrifugation at a saline density of 1.26 g/ml. It exhibited lipoprotein characteristics with an approximate protein/lipid ratio of 1.22 and free fatty acids and phosphatidylcholine as its main lipid components. Linoleic acid desaturation activity diminished in washed microsomes, since they lost the adsorbed cytosolic fraction. Addition of the factor reactivated the reaction and the recovery was dependent on the concentration of the factor in the medium. Linoleic acid and linoleyl-CoA were bound by the cytosolic fraction. However, the transport of substrate to the desaturase was not apparently a main function of the cytosolic fraction, since transport occurred equally in the absence of the factor. Moreover, the solubilization of linoleyl-CoA was not enhanced and the free monomeric concentration was not altered by the presence of the cytosolic fraction. In addition, the factor did not divert delta 6-desaturase substrate to or from other metabolic pathways such as esterification to phospholipids. gamma-Linolenic acid produced by delta 6-desaturation of linoleic acid in the microsomes inhibited the desaturase, but it was removed by the factor from the membrane towards the cytosol, preventing the inhibition. The anti-inhibitory effect of the cytosolic factor was blockaded by addition of columbinic acid or gamma-linolenic acid to the factor. Moreover, the inhibitory effect of arachidonic acid was not prevented by addition of the cytosolic fraction. These results suggest that the cytosolic fraction studied would optimize the delta 6-desaturation of linoleic acid in vitro in rat liver microsomes by removal of the product, gamma-linolenic acid, as it is formed.
Leikin
A I
AI
Brenner
R R
RR
D000818:Animals; D002250:Carbon Radioisotopes; D002458:Cell Fractionation; D003600:Cytosol / Q000201:enzymology; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008042:Linolenic Acids / Q000378:metabolism; D050602:Linoleoyl-CoA Desaturase; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017962:alpha-Linolenic Acid
D002250:Carbon Radioisotopes; D008041:Linoleic Acids; D008042:Linolenic Acids; D017962:alpha-Linolenic Acid; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase