The importance of the stearoyl-CoA desaturase system in octadecenoate metabolism in the Morris hepatoma 7288C.
The sources of octadecenoic acid (18:1) and the importance of the stearoyl-CoA desaturase system in maintaining elevated levels of this fatty acid in the Morris hepatoma 7288C have been investigated. Sterculic acid, an inhibitor of the stearoyl-CoA desaturase system, when added to the culture medium, inhibited the production of monoenoic fatty acids through de novo synthesis by 90% while the production of saturated fatty acids and cholesterol was unaffected. Sterculic acid also inhibited 18:1 formation through desaturation of exogenous stearate (18:0) by 80%. These results indicate that the stearoyl-CoA desaturase system is responsible for most, if not all, of the 18:1 produced within these cells and that an alternate, sterculic acid-insensitive, pathway for 18:1 biosynthesis is not functioning in this cell line. Measurements of fatty acid synthesis, using 3H2O, show that de novo synthesis accounts for approx. 30% of the cellular 16:1 and 18:1 mass, while contributing 63% and 95% of the stearate and palmitate mass, respectively. Cells grown in the presence of sterculic acid displayed a 50% decrease in 18:1 levels while levels of both palmitate and stearate increased. These effects were maximal at 20-30 microM sterculate. Polyunsaturate levels were unaffected. The 50% decrease in 18:1 levels in treated cells could be completely accounted for by the inhibition of de novo 18:1 biosynthesis and the inhibition of exogenous 18:0 desaturation. This enzyme system, although low in activity when measured in this tissue, is responsible for a major portion of the 18:1 observed in these cells.
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003521:Cyclopropanes / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005994:Glycerophosphates / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D003521:Cyclopropanes; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D005994:Glycerophosphates; D009829:Oleic Acids; D019301:Oleic Acid; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C003345:sterculic acid