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Thia fatty acids as substrates and inhibitors of stearoyl-CoA desaturase

1997; Elsevier BV; Volume: 1349; Issue: 3 Linguagem: Inglês

10.1016/s0005-2760(97)00135-5

1879-145X

Kjerstin Elisabeth Høvik, Øystein Spydevold, Jon Bremer,

Cholesterol and Lipid Metabolism

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 Δ9 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 Δ9 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.