Human serum albumin (HSA) is the major protein component of blood plasma and serves as a transporter for thyroxine and other hydrophobic compounds such as fatty acids and bilirubin. We report here a structural characterization of HSA-thyroxine interactions. Using crystallographic analyses we have identified four binding sites for thyroxine on HSA distributed in subdomains IIA, IIIA, and IIIB. M...

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calcula...

While the rBle of thyroxine in the body’s growth, development, and maintenance is important, as yet no definitive mechanism or locus of action for it has been delineated. In a recent review, Barker (1) has considered many of the enzymatic phenomena associated with different thyroidal states, and it is obvious from a consideration of the effects of this hormone that its action has wide-spread ra...

Studies of the metabolism of thyroxine in 14 cases of cirrhosis revealed a variety of deviations from normal. In addition to radiothyroxine turnover studies, determinations were made of the free thyroxine fractions and free thyroxine iodine concentrations in serum (magnesium precipitation method) as well as the maximal binding capacities of thyroxine-binding alpha globulin (TBG) and thyroxine-b...

In ecological models, the timing of amphibian metamorphosis is dependent upon rate of larval growth, e.g., tadpoles that experience a decrease in growth rate can initiate metamorphosis early. Recent authors have suggested that this plasticity may be lost at some point during the larval period. We tested this hypothesis by exposing groups of tadpoles of the gray treefrog, Hyla versicolor, to dif...

We describe a simple method for evaluating thyroxine-binding globulin capacity and concentration from a single 1-cm blood spot on filter-paper used in a screening program for neonatal hypothyroidism. This method permits prompt diagnosis of about 90% of the infants with thyroxine-binding globulin deficiency in our abnormal low-thyroxine, low-thyrotropin population. There was excellent equivalenc...

A simple test of in vitro thyroxine binding to serum proteins was used to screen serum samples from euthyroid patients with unexplained increases in the free thyroxine index. A diagnosis of familial dysalbuminaemic hyperthyroxinaemia was presumed in 14 unrelated subjects and six first degree relatives. Increased binding of thyroxine to thyroxine binding prealbumin was diagnosed in one woman wit...

The familial dysalbuminemic hyperthyroxinemia (FDH) phenotype results from a natural human serum albumin (HSA) mutant with histidine instead of arginine at amino acid position 218. This mutation results in an enhanced affinity for thyroxine. Site-directed mutagenesis and a yeast protein expression system were used to synthesize wild type HSA and FDH HSA as well as several other HSA mutants. Stu...