Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of temperature on the binding of thyroxine and triiodothyronine to thyroxine-binding globulin has been studied by equilibrium dialysis. Inclusion of ovalbumin in the dialysis mixture stabilized thyroxine-binding globulin against losses in binding activity which had been found to occur during equilibrium dialysis. Ovalbumin by itself bound the thyroid hormones very weakly and its binding could be neglected when analyzing the experimental results. At pH 7.4 and 37 degrees in 0.06 M potassium phosphate/0.7 mM EDTA buffer, thyroxine was bound to thyroxine-binding globulin at a single binding site with apparent association constants: at 5 degrees, K = 4.73 +/- 0.38 X 10(10) M-1; at 25 degrees, K = 1.55 +/- 0.17 X 10(10) M-1; and at 37 degrees, K = 9.08 +/- 0.62 X 10(9) M-1. Scatchard plots of the binding data for triiodothyronine indicated that the binding of this compound to thyroxine-binding globulin was more complex than that found for thyroxine. The data for triiodothyronine binding could be fitted by asuming the existence of two different classes of binding sites. At 5 degrees and pH 7.4 nonlinear regression analysis of the data yielded the values n1 = 1.04 +/- 0.10, K1 = 3.35 +/- 0.63 X 10(9) M-1 and n2 = 1.40 +/- 0.08, K2 = 0.69 +/- 0.20 X 10(8) M-1. At 25 degrees, the values for the binding constants were n1 = 1.04 +/- 0.38, K1 = 6.5 +/- 2.8 X 10(8) M-1 and n2 = 0.77 +/- 0.22, K2 = 0.43 +/- 0.62 X 10(8) M-1. At 37 degrees where less curvature was observed, the estimated binding constants were n1 = 1.02 +/- 0.06, K1 = 4.32 +/- 0.59 X 10(8) M-1 and n2K2 = 0.056 +/- 0.012 X 10(8) M-1. When n1 was fixed at 1, the resulting values obtained for the other three binding constants were at 25 degrees, K1 = 6.12 +/- 0.35 X 10(8) M-1, n2 = 0.72 +/- 0.18, K2 = 0.73 +/- 0.36 X 10(8) M-1; and at 37 degrees K1 = 3.80 +/- 0.22 X 10(8) M-1, n2 = 0.44 +/- 0.22, and K2 = 0.43 +/- 0.38 X 10(8) M-1. The thermodynamic values for thyroxine binding to thyroxine-binding globulin at 37 degrees and pH 7.4 were deltaG0 = -14.1 kcal/mole, deltaH0 = -8.96 kcal/mole, and deltaS0 = +16.7 cal degree-1 mole-1. For triiodothyronine at 37 degrees, the thermodynamic values for binding at the primary binding site were deltaG0 = -12.3 kcal/mole, deltaH0 = -11.9 kcal/mole, and deltaS0 = +1.4 cal degree-1 mole-1. Measurement of the pH dependence of binding indicated that both thyroxine and triiodothyronine were bound maximally in the region of physiological pH, pH 6.8 to 7.7.
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PMID:Thyroxine-protein interactions. Interaction of thyroxine and triiodothyronine with human thyroxine-binding globulin. 0 58

It has been previously suggested that inherited thyroxine-binding globulin (TBG) abnormalities in man may be due to mutations at a single X-chromosome-linked locus controlling TBG synthesis. However, abnormalities in TBG degradation have not been excluded. The availability of purified human TBG and its successful labeling with radioiodide allowed us to examine such possibility. Human TBG was purified by affinity chromatography, labeled under sterile conditions with 131I or 125I,, and mixed with [125I]thyroxine (T4) or [131I]T4, respectively, before their intravenous injection. Blood and urine samples were collected over a 10-day period, and the turnover parameters were calculated. In eight normal volunteers mean values +/-SD for TBG and T4 respectively, were as follows: Half time (t1/2) 5.3 +/- 0.4 and 7.0 +/- 0.6 days; distribution space (DS) 7.2 +/- 1.0 and 10.8 +/- 1.2 liters; and total daily degradation (D) 0.211 +/- 0.053 and 0.088 +/- 0.011 mumol/day. In all subjects, t1/2 of TBG was shorter than that of T4; and the DS was smaller. 2.4 mol of TBG was degraded for each mole of T4. In five of six subjects from four families, comprising hemizygous and heterozygous carriers of TBG absence, decrease, and excess, the t1/2 and DS for TBG were within the normal range. The D of TBG was proportional to the serum concentration of the protein. Changes in the T4 kinetics in these patients were compatible with euthyroidism and with the known alterations in the extrathyroidal T4 pool associated with the changes in serum TBG concentration. A striking decrease in the t1/2 of TBG was found only in a patient with acquired diminution in TBG concentration and in patients with thyrotoxicosis or other conditions apparently unrelated to thyroid dysfunction. TBG t1/2 was 2.5 days in a patient with multiple myeloma and 3.6 days in two patients with thyrotoxicosis. Decreased TBG t1/2 was also observed in three of six patients with nonthyroidal pathology and was associated with an increase in TBG D disproportionate to their level of serum TBG. These studies indicate that changes in TBG concentration in patients with X-chromosome-linked TBG abnormalities are due to alterations in its rate of synthesis. In other conditions, abnormalities of TBG degradation and/or rate of synthesis may be found.
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PMID:Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess. 5 42

The authors have set up a thyroxine-binding-globulin radio-immunoassay in blood serum. The standard used has been determined by gravimetry, its maximal thyroxine-binding capacity is 0,96 mole of thyroxine per mole of TBG. Serum concentration of TBG has been measured in 159 euthyroid normals. The mean value of the concentration is 20 mg/l.
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PMID:[Radioimmunoassay of serum thyroxin-binding-globulin in euthryoid subjects]. 41 54

Studies of several aspects of thyroid hormone economy have been conducted in 11 patients before and after removal of a molar pregnancy. Before evacuation of the mole, all patients demonstrated moderately to greatly elevated values for thyroidal (131)I uptake, absolute iodine uptake, and serum protein-bound-(131)I. Values for serum PBI and serum thyroxine (T(4)) concentration were consistently and often greatly increased, averaging more than twice those found in normal pregnancy and three times those in normal controls. On the other hand, the maximum binding capacity of the T(4)-binding globulin (TBG) was variably affected, and ranged between the values found in normal controls and those found in normal pregnancy. Values for the absolute concentration of free T(4) in serum were, on the average, only moderately elevated, since the proportion of free T(4) was moderately low, although not as low as in normal pregnancy. Sera of patients with molar pregnancy contained high levels of thyroid stimulating activity, as assessed in the McKenzie mouse bioassay system. The stimulator displayed a more prolonged duration of action than that of TSH and did not reveal a major immunological cross-reactivity with either human or bovine TSH, differing in the latter respect from the chorionic thyrotropin of normal human placenta. Abnormalities in iodine metabolism were rapidly ameliorated after removal of the molar pregnancy, and this was associated with the disappearance from serum of the thyroid stimulator. Despite the foregoing evidence of thyroid hyperfunction and hypersecretion of T(4), patients with molar pregnancy were neither goitrous nor overtly thyrotoxic. They did display, however, high values of the urinary pigment/creatinine ratio, a possible indication of the presence of a hypermetabolic state. It is concluded that in patients with molar pregnancy, thyroid function and T(4) secretion are stimulated, often greatly so, by an unusual thyroid stimulator which is demonstrable in the blood and which is probably of molar origin. The nature of the stimulator, as well as the reasons for both the variability of the increase in TBG which occurs in molar pregnancy and the lack of frank thyrotoxicosis, remain to be clarified.
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PMID:Alterations in thyroid hormone economy in patients with hydatidiform mole. 410 51

The production of TBG in liver increases during pregnancy. The thyroid stimulating substance is also suggested to exist in molar pregnancy. We have studied the thyroid functions with T4, T3, T3 resin uptake, TBG, free T4, TSH, HCG, TBG binding capacity and T4 binding by TBG in non-pregnant women, pregnant women and molar pregnant women. T4 and T3 levels were high during pregnancy and remarkably elevated in mole. TBG levels were 49.0 +/- 5.1/micrograms/ml in 3rd. trimester, which were 2.6 times higher than non-pregnant women and 38.4 +/- 8.4 micrograms/ml in mole. Res-O-Mat T3 values distributed within normal levels in 1st trimester and mole and higher in 3rd. trimester. Free T4 indices were almost normal during pregnancy and 2.4 times higher in mole. Free T4 levels, measured with dialysis and RIA, were slightly low during pregnancy but remarkably high in mole. Basal TSH levels were within normal range for these subjects. Beta-HCG levels in mole were greatly in excess of peak concentrations that were seen at 9-13 weeks of normal pregnancy. The significant correlations of beta-HCG with T4, T3 and free T4 index were found in mole, with coefficient of r = 0.691, 0.687, 0.644 respectively. The correlations of beta-HCG with free T4 and TBG were also suggested in mole. The levels of T4 binding by TBG were remarkably elevated for incremental TBG in mole, which pattern was particular for thyroid hyperfunction. From the above results, we considered that euthyroidism is sustained during pregnancy and thyroid stimulating substance existed in mole. That substance is probably HCG, which is remarkable elevated in mole.
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PMID:[T4, T3, T3 resin uptake, TBG and free T4 levels for thyroid functions in normal and molar pregnancy (author's transl)]. 680 12