Influence of nonesterified fatty acids and lysolecithins on thyroxine binding to thyroxine-binding globulin and transthyretin.
The hydrolysis of lecithin by phospholipase produces equimolar amounts of nonesterified fatty acids (NEFAs) and lysolecithin. In this study, we have evaluated the effect of lysolecithins and NEFAs on thyroid hormone binding by examining their interactions with thyroxine-binding globulin (TBG)(serum 1:10,000 dilution) and purified transthyretin (TTR). Unsaturated NEFAs (palmitoleic, oleic, linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acid) inhibited [125I]T4 binding to TBG. Their affinities, relative to unlabeled T4, ranged from 0.005 to 0.0016%, except for oleic acid with relative affinity of < 0.0005%. Saturated NEFAs, lauric, myristic, palmitic, and stearic acid were inactive. After purification by high-performance liquid chromatography, 1-oleoyl and 2-oleoyl lysolecithin displaced [125I]T4 from TBG with an affinity of 0.0006 and 0.0005%, respectively. On a molar basis, this affinity was approximately 10-fold lower than arachidonic acid, the most potent NEFA in inhibiting T4 binding to TBG in this assay system. Of all the NEFAs tested, only arachidonic acid inhibited [125I]T4 binding to TTR, with an affinity relative to unlabeled T4 of 0.49%. 1-Oleoyl, 1-palmitoyl, and 1-stearoyl lysolecithin were without effect on TTR binding. The T4-displacing effects of NEFAs are markedly attenuated by their extensive binding to albumin. Using purified [14C]NEFA preparations and heptane partitioning, the mean unbound percentages of linoleic, eicosapentaenoic, and docosahexaenoic acid in undiluted normal human serum were 0.00099, 0.0050, and 0.0042%, respectively (n = 3). In view of the very high degree of albumin binding of NEFAs, studies in diluted serum will grossly overestimate their competitor potency. The affinities of lysolecithins for the T4 binding sites of TBG and TTR are lower than those of NEFAs and depend on the fatty acid component. Lysolecithins are unlikely to influence plasma protein binding of T4 during critical illness.
D016718:Arachidonic Acid / Q000494:pharmacology; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D011228:Prealbumin / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism*; D013975:Thyroxine-Binding Proteins / Q000378:metabolism*
D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D007457:Iodine Radioisotopes; D008244:Lysophosphatidylcholines; D011228:Prealbumin; D012709:Serum Albumin; D013975:Thyroxine-Binding Proteins; D016718:Arachidonic Acid; D013974:Thyroxine