Effect of long-chain fatty acids on the binding of thyroxine and triiodothyronine to human thyroxine-binding globulin

Abstract

The effect of long-chain fatty acids on the binding of thyroxine to highly purified human thyroxine-binding globulin has been studied by equilibrium dialysis performed at pH 7.4 and 37°C. At a fixed molar ratio of 2000 : 1 of fatty acid to thyroxine-binding globulin, the degree of binding inhibition based on the percent change in nK value relative to the control as determined from Scatchard plots was: palmitic .0%; stearic, 0%; oleic, 76%; linoleic, 69%; and linolenic, 61%. At a 500 : 1 molar ratio of oleic acid to thyroxine-binding globulin, equivalent to 0.125 mM free fatty acid in serum, thyroxine binding was inhibited by 18%, increasing to 93% at a 4500 : 1 molar ratio. At molar ratios of oleic to thyroxine-binding globulin of 1000 : 1, 2000 : 1 and 4000 : 1, the degree of inhibition of triiodothyronine binding was 24%, 41% and 76%, respectively. The results indicate that the unsaturated long-chain fatty acids are potent inhibitors of thyroxine binding to thyroxine-binding globulin, whereas the saturated fatty acids have little or no effect on thyroxine binding.