Microsomal delta 5 desaturation of eicosa-8,11,14-trienoic acid is activated by a cytosolic fraction.
delta 5 Desaturation of eicosa-8,11,14-trienoic acid to arachidonic acid was studied in rat liver microsomes. It was shown that delta 5 desaturation of fatty acids in vitro requires the participation of a peripheral component of cytosolic origin. Desaturation of 20:3n-6 to 20:4n-6 decreases in washed microsomes as they lose an adsorbed cytosolic fraction (CF), but the enzymatic activity can be recovered as a function of CF concentration in the incubation medium. Albumin does not substitute for CF. delta 5 Desaturation of 20:3n-6 is inhibited by arachidonic acid by a product inhibition effect, but CF prevents retroinhibition of delta 5-desaturase by 20:4n-6. This ability of CF is eliminated by preincubation of CF with 20:4n-6, but not with gamma-18:3n-6, the product of delta 6 desaturation of 18:2n-6, thus indicating that CF impairs the retroinhibitory effect of arachidonic acid on delta 5-desaturase in a specific manner. delta 6 Desaturation of linoleic acid to gamma-18:3n-6 is also activated by CF and retroinhibited by gamma-18:3n-6. CF activity on delta 6 desaturation is retained after preincubation with 20:4n-6, but it is lost after preincubation with gamma-18:3n-6. Activation of delta 6-desaturase by CF is associated with the removal of the reaction product in a specific manner. Chromatography of CF by Sephacryl S-200 separates two major subfractions which show different efficiency in reactivating delta 5- and delta 6-desaturase activities in washed microsomes. Therefore, CF may contain subfractions that can prevent delta 5- and delta 6-desaturase retroinhibition by apparently binding their respective reaction products specifically.
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, Facultad de Ciencias Médicas, Argentina.
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Leikin
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Brenner
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D000090943:Delta-5 Fatty Acid Desaturase; D004789:Enzyme Activation; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D050602:Linoleoyl-CoA Desaturase; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000494:pharmacology
D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D014020:Tissue Extracts; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; D015126:8,11,14-Eicosatrienoic Acid