Thia fatty acids as substrates and inhibitors of stearoyl-CoA desaturase.
Thia fatty acids are fatty acid analogues, where sulfur atoms substitute methylene groups in the carbon chain. In 7800 C1 Morris hepatoma cells and in hepatocytes 9-thia and 10-thia stearic acid are strong inhibitors of stearoyl-Co desaturase, while 3,9-dithia stearic acid and 3,10-dithia stearic acid are much weaker inhibitors. No effect on the stearoyl-CoA desaturase can be observed with 3-thia stearic acid. In microsomes, an equimolar concentration of 9-thia stearoyl-CoA inhibits the delta9 desaturation of [1-14C]stearoyl-CoA approximately 75%, while 3,9-dithia stearoyl-CoA and 3,10-dithia stearoyl-CoA again are weak inhibitors. 3-Thia stearoyl-CoA has no effect on the desaturation of [1-14C]stearoyl-CoA. [2-14C]3-Thia stearoyl-CoA is delta9 desaturated to [2-14C]thia oleic acid. This desaturation is inhibited by unlabelled stearoyl-CoA, which therefore is the preferred substrate. These results show that a sulfur atom in the 3 position reduces the affinity of the CoA ester for the enzyme, but permits desaturation. A sulfur in the 9 or 10 position does not affect binding to the enzyme. The 9-thia and 10-thia stearoyl-CoA, which cannot be desaturated, therefore are strong inhibitors.
Høvik
K E
KE
Institute of Medical Biochemistry, University of Oslo, Norway.
Spydevold
O S
OS
Bremer
J
J
D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D019301:Oleic Acid / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013229:Stearic Acids / Q000378:metabolism* / Q000494:pharmacology; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D013457:Sulfur Compounds / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; D013229:Stearic Acids; D013457:Sulfur Compounds; D019301:Oleic Acid; C017725:stearoyl-coenzyme A; D013230:Stearoyl-CoA Desaturase