Dependence of the thyroxin/thyroxin-binding globulin (TBG) ratio and the free thyroxin index on TBG concentrations.

1989 ◽  
Vol 35 (4) ◽  
pp. 541-544 ◽  
Author(s):  
J C Nelson ◽  
R T Tomei
Keyword(s):  
Binding Proteins ◽  
Free Fraction ◽  
The Other ◽  
Free T4 ◽  
Clinical Interest

Abstract We studied the dependence of the free thyroxin (T4) index and the ratio of T4 to thyroxin-binding globulin (TBG) on TBG concentrations, using sera from cases of congenital TBG deficiency and congenital TBG excess. Two such sera with similar concentrations of albumin, transthyretin, and free T4 were mixed to provide test samples with TBG concentrations covering the range of clinical interest without changes in the other T4-binding proteins. Total T4, free T4, TBG, triiodothyronine (T3) uptake, and the free fraction of T3 in serum were measured, and we calculated the free T4 indices, T4/TBG ratios, and the free fraction of T4. A 100-fold variation in TBG concentration was associated with a 10-fold variation in total T4, a fourfold variation in T3 uptake, and a 10-fold variation in the T4/TBG ratio. As TBG concentrations increased, the T4/TBG ratio decreased and the free T4 index increased. The free T4 index did not parallel the T4/TBG ratio, and neither the T4/TBG ratio nor the free T4 index reflected the concentrations of free T4 in serum.

The Transport of Thyroid Hormones

1983 ◽  
Vol 65 (4) ◽  
pp. 337-342 ◽  
Author(s):  
R. Hoffenberg ◽  
D. B. Ramsden
Keyword(s):  
Thyroid Hormones ◽  
Binding Proteins ◽  
Serum Proteins ◽  
High Capacity ◽  
Free Fraction ◽  
Total Serum ◽  
Free T4 ◽  
Specific Serum ◽  
Target Organs ◽  
Serum T4

1. Hormones have to be transported from their sites of synthesis to their target organs. For lipophilic hormones, such as steroids and thyroid hormones, transport is accomplished by binding to specific serum proteins, in the case of thyroxine (T4) and tri-iodothyronine (T3) to thyroxine-binding globulin (TBG) and prealbumin (PA). Normally about 70% of circulating T4 and 75–80% of T3 is bound to TBG, about 20% of T4 and 10% of T3 to PA and 10–15% of each to albumin, which has a low affinity but high capacity for both hormones [1, 2]. Apart from facilitating transport, binding to serum protein prevents excessive loss of hormone into the urine by glomerular filtration or flooding into cells, and may provide a readily available reservoir in times of need. The union between binding proteins and their ligands is reversible, so that a small proportion of hormone is non-protein-bound or ‘free’, in equilibrium with that which is protein-bound. For T4 this free fraction is normally 0.02-0.04% of the total serum T4 concentration, for T3 about 0.3% [3, 4]. 2. The major binding proteins of T4 and T3 will briefly be described and the nature of free T4 and T3 considered.

Effect of Sodium Ethylmercurithiosalicylate (Thimerosal) on Serum Binding of Thyroid Hormones

1973 ◽  
Vol 51 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Diego Bellabarba ◽  
Raymonde Tremblay
Keyword(s):  
Thyroid Hormones ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Free Fraction ◽  
Inhibitory Effect ◽  
Free T4 ◽  
Thyroxine Binding Globulin ◽  
Free T3 ◽  
Serum Binding Protein ◽  
Barbital Buffer

Sodium ethylmercurithiosalicylate (Thimerosal, Merthiolate) has been found to interfere with the binding of thyroid hormones to serum proteins. Dialysis studies showed that this compound, added to serum in concentrations varying from 90 to 360 mg/100 ml, caused an increase of the dialyzable or free fraction of thyroxine (T4) and triiodothyronine (T3). The increase was higher for the free T4 (3.8- to 18-fold) than for the free T3 fraction (2.3- to 5-fold). Electrophoretic studies on the distribution of tracer amounts of labeled T4 among the serum binding proteins revealed that the inhibitory effect of sodium ethylmercurithiosalicylate was exerted mainly on thyroxine binding globulin (TBG). In presence of this compound (180 mg/100 ml of serum) the percentage of tracer T4 bound to TBG was reduced from 53% to 9%. These findings were also confirmed by examining the binding of tracer amounts of labeled T4 and T3 in a serum diluted in barbital buffer, which inhibits the hormonal binding to thyroxine binding prealbumin and albumin. In presence of sodium ethylmercurithiosalicylate a significant displacement of both T4 and T3 from the serum binding protein (TBG) was observed.

Dynamic localization of penicillin-binding proteins during spore development in Bacillus subtilis

Microbiology ◽  
2005 ◽  
Vol 151 (3) ◽  
pp. 999-1012 ◽  
Author(s):  
Dirk-Jan Scheffers
Keyword(s):  
Bacillus Subtilis ◽  
Green Fluorescent Protein ◽  
Binding Proteins ◽  
Cytoplasmic Membrane ◽  
Fluorescent Protein ◽  
Spore Formation ◽  
The Other ◽  
Spore Development ◽  
Penicillin Binding Proteins ◽  
Green Fluorescent

During Bacillus subtilis spore formation, many membrane proteins that function in spore development localize to the prespore septum and, subsequently, to the outer prespore membrane. Recently, it was shown that the cell-division-specific penicillin-binding proteins (PBPs) 1 and 2b localize to the asymmetric prespore septum. Here, the author studied the localization of other PBPs, fused to green fluorescent protein (GFP), during spore formation. Fusions to PBPs 4, 2c, 2d, 2a, 3, H, 4b, 5, 4a, 4* and X were expressed during vegetative growth, and their localization was monitored during sporulation. Of these PBPs, 2c, 2d, 4b and 4* have been implicated as having a function in sporulation. It was found that PBP2c, 2d and X changed their localization, while the other PBPs tested were not affected. The putative endopeptidase PbpX appears to spiral out in a pattern that resembles FtsZ redistribution during sporulation, but a pbpX knockout strain had no distinguishable phenotype. PBP2c and 2d localize to the prespore septum and follow the membrane during engulfment, and so are redistributed to the prespore membrane. A similar pattern was observed when GFP–PBP2c was expressed in the mother cell from a sporulation-specific promoter. This work shows that various PBPs known to function during sporulation are redistributed from the cytoplasmic membrane to the prespore.

Modeling thyroxine transport to liver: rejection of the "enhanced dissociation" hypothesis as applied to thyroxine

1989 ◽  
Vol 257 (5) ◽  
pp. E764-E771
Author(s):  
C. M. Mendel
Keyword(s):  
Steady State ◽  
Binding Proteins ◽  
Surface Membrane ◽  
Hepatic Uptake ◽  
Data Uncertainty ◽  
Free T4 ◽  
Influx Rate ◽  
Steady State Kinetics ◽  
Uptake Data

Three models for the hepatic uptake of thyoxine (T4) from human plasma were considered: 1) uptake occurs exclusively via the pool of free T4 after spontaneous dissociation of T4-plasma-protein complexes, 2) uptake occurs primarily via the pool of bound T4 by the interaction of one or more binding proteins with the cell-surface membrane, and 3) uptake occurs primarily by "enhanced dissociation" of T4 from one or more of its binding proteins within the sinusoids. Each of these models was examined in relation to well-accepted unidirectional uptake and steady-state kinetics data that indicate that 1) between 4 and 24% of the T4 in normal human serum is taken up unidirectionally by the liver in a single pass, and 2) the in vivo disposal rate of T4 is unaffected by primary changes in the plasma concentration of thyroid hormone-binding globulin. Both analytical and numerical techniques were used. The first two models were found to be compatible with both the steady-state kinetics data and the unidirectional uptake data, given certain assumptions in each of the models. Although theoretically distinguishable on the basis of unidirectional uptake data, uncertainty over the true uptake (influx) rate constant for free T4 prevented resolution between these two models. In contrast, the third model, that of enhanced dissociation [W. M. Pardridge, Am. J. Physiol. 252 (Endocrinol. Metab. 15): E157-E164, 1987], was found, as currently formulated with respect to T4, to be incompatible with both the steady-state kinetics data and the unidirectional uptake data.(ABSTRACT TRUNCATED AT 250 WORDS)

Free triiodothyronine and free thyroxin in sera of pregnant women and subjects with congenitally increased or decreased thyroxin-binding globulin.

1983 ◽  
Vol 29 (8) ◽  
pp. 1527-1530 ◽  
Author(s):  
J A Franklyn ◽  
M C Sheppard ◽  
D B Ramsden ◽  
R Hoffenberg
Keyword(s):  
Pregnant Women ◽  
Binding Proteins ◽  
Free Triiodothyronine ◽  
Free T4 ◽  
Free T3 ◽  
Low Concentrations ◽  
Euthyroid Status ◽  
In Pregnancy

Abstract Concentrations of free thyroxin (T4) and free triiodothyronine (T3) were measured in sera from pregnant women, in subjects with congenitally increased or decreased thyroxin-binding globulin (TBG), and in euthyroid controls. Measured free hormone concentrations were compared with calculated values for free hormone derived from concentrations of total T4, total T3, and binding proteins. Measured and calculated concentrations of free T4 and free T3 were below normal in the pregnant subjects but were normal in subjects with congenital increases of TBG. The low concentrations of free hormone in pregnancy are at variance with the euthyroid status of these subjects. Measured free T4 was normal, but concentrations of free T3 were less in the euthyroid congenitally low-TBG group.

scholarly journals Affinities of β-Lactams for Penicillin Binding Proteins of Chlamydia trachomatis and Their Antichlamydial Activities

2001 ◽  
Vol 45 (1) ◽  
pp. 303-305 ◽  
Author(s):  
Christopher Storey ◽  
Ian Chopra
Keyword(s):  
Chlamydia Trachomatis ◽  
Binding Proteins ◽  
Inhibitory Concentration ◽  
Minimum Bactericidal Concentration ◽  
The Other ◽  
Binding Affinities ◽  
Penicillin Binding Proteins

ABSTRACT Binding affinities of β-lactam antibiotics for the three penicillin binding proteins (PBPs) from Chlamydia trachomatis were determined in vitro and compared with their antichlamydial activities. Mecillinam selectively inhibited PBP1, with a 50% inhibitory concentration for PBP1 binding (0.2 μg/ml) similar to the MIC (0.1 μg/ml) and minimum bactericidal concentration (0.25 μg/ml). Although the other β-lactams inhibited a wider range of PBPs than mecillinam, their antichlamydial activities were inferior to that of mecillinam.

Ampicillin resistance in Neisseria denitrificans: studies on ampicillin-sensitive enzymes

1981 ◽  
Vol 27 (5) ◽  
pp. 553-557
Author(s):  
C. R. MacKenzie ◽  
I. J. McDonald ◽  
K. G. Johnson
Keyword(s):  
Growth Phase ◽  
Binding Proteins ◽  
The Other ◽  
Ampicillin Resistance ◽  
Peptidoglycan Synthesis ◽  
Resistant Cells

The β-lactam sensitivities of enzymes involved in peptidoglycan synthesis were examined in two strains of Neisseria 'enitrificans having widely disparate degrees of ampicillin sensitivity. One strain of N. denitrificans was 400 times more resistant) ampicillin than the other; the former is known to have altered pencillin-binding proteins. No differences in the levels of ensitivities of total peptidoglycan synthesis as measured by the incorporation of glutamate into peptidoglycan, or of D-alanine arboxypeptidase, were observed between the two strains. However, the rate of glutamate incorporation into peptidoglycan by garithmic growth phase cells was somewhat less for the ampicillin-resistant cells than for the parent cells.

scholarly journals Cobalamin (vitamin B12) and B12 binding proteins in hypereosinophilic syndromes and secondary eosinophilia

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 779-783
Author(s):  
J Zittoun ◽  
JP Farcet ◽  
J Marquet ◽  
C Sultan ◽  
R Zittoun
Keyword(s):  
Vitamin B12 ◽  
Binding Proteins ◽  
Binding Capacity ◽  
Hypereosinophilic Syndrome ◽  
Elevated Serum ◽  
Serum Vitamin ◽  
Myeloproliferative Disorders ◽  
The Other ◽  
Intracellular Content ◽  
Eosinophil Counts

Serum cobalamin (vitamin B12) and unsaturated B12 binding capacity (UBBC) have been measured in 24 cases of hypereosinophilia: 16 were cases of hypereosinophilic syndrome (HES) and 8 of secondary eosinophilia. The two groups were similar with respect to absolute eosinophil counts. Serum cobalamin and UBBC were found to be markedly increased in most cases of HES and normal in secondary eosinophilia. This elevation of UBBC was mainly related to the increase of R binders (transcobalamins I and III). The elevated serum cobalamin and R binders in HES were due neither to a higher intracellular content of R binders nor to an increased release of these binders from eosinophils of HES. Pure fractions of eosinophils obtained from HES and secondary eosinophilia did not exhibit any difference in vitamin B12 binders. On the other hand, neutrophil-rich fractions from the same patients showed a higher content of intracellular B12 binding proteins than pure eosinophil fractions, irrespective of the cause of eosinophilia. These findings suggest that the increased serum vitamin B12 and UBBC could reflect an expanded pool of both eosinophils and neutrophils in HES and, thus, provide an additional argument for the inclusion of this syndrome in the group of myeloproliferative disorders.

SOLUBILIZATION AND PARTIAL CHARACTERIZATION OF THYROID MEMBRANE TSH BINDING PROTEINS

1979 ◽  
Vol 92 (3) ◽  
pp. 512-521 ◽  
Author(s):  
B. Czarnocka ◽  
J. Nauman ◽  
G. Adler ◽  
W. Kiełczyński
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Binding Proteins ◽  
Gel Filtration ◽  
Soluble Proteins ◽  
The Other ◽  
High Affinity ◽  
Triton X ◽  
Maximal Capacity

ABSTRACT Crude plasma membranes obtained from bovine thyroids were found to possess one class of high affinity, low capacity binding sites for TSH with average association constant (Ka) of 1.301 × 109 m−1 and maximal capacity 8.76 × 10−10 m/mg of protein. Treatment of crude membranes fraction with 0.1 % Triton X-100 and the subsequent sonication in ultrasonic disintegrator resulted in solubilization of membranes proteins with mean recovery of 40.0 ± 6.2 %. Soluble proteins retained the property to bind [125I]TSH, but the binding of the hormone was decreased. The removal of the detergent from the solubilizate by gel filtration on Sephadex LH-20 increased the binding of TSH well above that demonstrated for crude thyroid membranes. The chromatography of soluble proteins on Ultrogel AcA-44 revealed the presence of two TSH binding proteins, one with the molecular weight (m.w.) above 130 000 daltons and the other with the m.w. approximately 30 000 daltons. The electrofocusing of solubilizate on Ampholine resulted in two protein peaks, one at pH 4.0–4.1 and the other at pH 4.4–4.6. The latter peak was shown to bind [125I]TSH specifically. The present results have confirmed the heterogeneous character of solubilized TSH receptor preparation and have shown that the hormone binding sites belong to acid proteins.

scholarly journals A Direct Free Thyroxine (T4) Immunoassay with the Characteristics of a Total T4 Immunoassay

2007 ◽  
Vol 53 (5) ◽  
pp. 911-915 ◽  
Author(s):  
Kristofer S Fritz ◽  
R Bruce Wilcox ◽  
Jerald C Nelson
Keyword(s):  
Serum Protein ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Equilibrium Dialysis ◽  
Free Thyroxine ◽  
Free T4 ◽  
Serum T4 ◽  
Presence And Absence

Abstract Background: Direct free thyroxine (T4) measurements have been linked to both T4-binding serum protein concentrations and protein-bound T4 concentrations. Whether this is evidence of a relationship to total T4 concentrations has not been reported. Methods: We compared an analog-based direct free T4 immunoassay and a total T4 immunoassay. Each assay was applied to the fractions of serum T4 obtained by ultrafiltration and equilibrium dialysis. Both were applied to serum-based solutions in which free T4, T4-binding proteins, protein-bound T4, and total T4 were systematically varied, held constant, or excluded. Results: Neither the free T4 assay nor the total T4 assay detected dialyzable or ultrafilterable serum T4. Both assays detected and reported the T4 retained with serum proteins. Both free and total T4 results were related to the same total T4 concentrations in the presence and absence of T4-binding proteins. Both results were similarly related to total T4 concentrations when free T4 was held constant while total T4 was varied. Both were similarly related to a total T4 concentration that was held constant while free T4 progressively replaced protein-bound T4. These free T4 results, like total T4 results, were unresponsive to a 500-fold variation in dialyzable T4 concentrations. Conclusion: New experiments extend the characterization of a longstanding and incompletely characterized analog-based free T4 immunoassay. These free T4 measurements relate to total T4 concentrations in the same way that total T4 measurements do.

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