The Binding of Androsterone Sulfate, Etiocholanolone Sulfate, and Dehydroisoandrosterone Sulfate by Human Plasma Protein*

Plager, John E.

doi:10.1172/jci105229

Cited by 60 publications

(31 citation statements)

References 12 publications

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“…The association constants for cortisol, testosterone, progesterone, and androsterone sulfate range from 3 X 10' to 3.6 X 10' liter/mole (26)(27)(28)(29)(30)(31). The binding is not as strong as that of thyroxine to albumin (k = 1.3 X 10' liter/mole) (32) or of the long-chain fatty acid anions, stearate, oleate, and palmitate, which have k values of 6 X 107-1.1 X 108 liter/mole (33).…”

Section: Resultsmentioning

confidence: 99%

Binding of digitoxin and some related cardenolides to human plasma proteins

Lukas¹,

Martino²

1969

J. Clin. Invest.

136

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A B S T R A C T Tritium-labeled digitoxin, digitoxigenin, digoxin, and digoxigenin of established purity and chemcal authenticity were used to study the binding of these compounds to human plasma proteins. 97% of digitoxin in plasma was nondialyzable. Continuous flow paper electrophoresis of plasma containing digitoxin and dialysis experiments in which human serum albumin competed for the glycoside with plasma or plasma protein fractions demonstrated that digitoxin was almost exclusively bound by albumin. Equilibrium dialyses revealed that the interaction was characterized by a single binding site on the albumin molecule and an association constant of 9.62 X 10' liter/mole at 370C. At 1VC the association constant was 4.64 X 10' liter/mole. The interaction therefore was endothermic; the gain in enthalpy of 3.5 kcal/mole and the free energy change of -7.06 kcal/ mole was derived from a large change in entropy of 33.8 cal/mole per 'K. The direction of these thermodynamic changes suggested the formation of a hydrophobic bond between digitoxin and albumin. Quenching of the fluorescence of albumin by digitoxin indicated that the conformation of albumin was altered by the binding process.Digitoxigenin, its mono-and didigitoxosides, digoxin, and digoxigenin competed with digitoxn for its binding site on albumin. The affinity of the mono-and didigitoxosides for the site was equal to that of digitoxin, but that of digitoxigenin was only one-third as great. The ability of the digitoxose residues of the glycosides to enhance binding to albumin was also observed with digoxin, Presented in part at the 28th Scientific Sessions of the American Heart Association, Miami Beach, Fla., 16 October 1965.Dr. De Martino was formerly a Postdoctoral Research Fellow of the National Heart Institute.Received for publication 15 November 1968 and in revised form 6 February 1969. which was more extensively bound by the protein than digoxigenin.At concentrations of 2 jg/ml or less in plasma, only 23% of digoxin was bound. Albumin, which interacted with digoxin with an apparent association constant of 9 X 102 liter/mole at 370C, was entirely responsible for the binding. Lowering the temperature from 370 to 1VC decreased the fraction of digoxin bound to albumin by two-thirds.The marked difference in avidity of digitoxin and digoxin for serum albumin is reflected by the higher plasma concentrations, lower rate of urinary excretion, and longer half-time of digitoxin as compared to those of digoxin when these compounds are administered to man.

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Section: Resultsmentioning

confidence: 99%

Binding of digitoxin and some related cardenolides to human plasma proteins

Lukas¹,

Martino²

1969

J. Clin. Invest.

136

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“…Binding to albumin in man has been demonstrated by Puche and Nes (20), Sandberg and Slaunwhite (21), and Plager (22). Puche and Nes, Plager, and Wang and Bulbrook (23) noted that all steroid sulfates tested competed for the same binding sites.…”

Section: Conversion Of Es To Es the Data Obtained Frommentioning

confidence: 87%

“…However, the association constants were influenced by the nature of the steroid. The association constant of DHS with albumin has been reported as 0.6-2 X 10' liter/mole (20,22), whereas the E1S binding constant was estimated at 2 X 104 liter/ mole (24). Although these binding affinities were not obtained in the same system, the association of lower affinity constants with higher volumes of distribution is apparent.…”

Section: Conversion Of Es To Es the Data Obtained Frommentioning

confidence: 97%

“…Although estrone sulfate has been identified in human urine, little is known of its blood levels and metabolism. Twombly and Levitz showed that estrone sulfate had a long halfReceived for publication 24 September 1971 and in revised form 22 November 1971. 1 Abbreviations used in this paper: DCC, dicyclohexylcarbodiimide; DHS, dehydroeipandrosterone sulfate; DMF, dimethyl formamide; E1, estone; E2, estradiol; E1S, estrone-3-sulfate; MCR, metabolic clearance rate; RBC, red blood cells; TLC, thin-layer chromatography.…”

Section: Introductionmentioning

confidence: 99%

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Estrone Sulfate: Production Rate and Metabolism in Man

Ruder¹,

Loriaux²,

Lipsett³

1972

J. Clin. Invest.

246

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A B S T R A C T Since estrone sulfate (E1S) is present at high concentration in plasma, we have examined the parameters of the plasma estrone, estradiol, E1S system. The metabolic clearance rate of EiS was 157 liter/day (range 70-292) in men and women. Estimated plasma production rates of E1S were (/Agrams per day): men, 77; women, early follicular phase, 95; women, early luteal phase, 182. The conversion of plasma estrone and estradiol to EiS was measured and from these data and the metabolic clearance rates of the estrogens, the transfer factors were p51'18 = 0.54 and p'2'1' = 0.65. Using average production rates, all plasma E1S could be shown to be derived from plasma estrone and estradiol.The conversion of plasma E1S to plasma estrone and estradiol was studied. The calculated transfer factors were: p'1`81 = 0.21, pBis2 = 0.014. Essentially, similar data were obtained when E1S was given by mouth to two subjects.We conclude: (a) EiS is a major circulating plasma estrogen and has a long plasma half-life; (b) the large contributions of estrone and estradiol to plasma E1S are more than sufficient to account for all the circulating plasma E1S.

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“…It should be noted that, in contrast to their unconjugated counterparts, cholesterol sulfate and DHEA sulfate are cleared slowly from the circulation with MCRs, respectively, of 10-17 l/day and 15-30 l/day (31,64). The slow clearance of these steroid sulfoconjugates from the circulation reflects their tight binding to plasma proteins, especially albumin (65). Importantly, although the sulfoconjugates of cholesterol and DHEA have similar PRs, they are, nevertheless, derived from different sources and have different metabolic routes.…”

Section: Synthesis and Metabolismmentioning

confidence: 99%

Cholesterol sulfate in human physiology: what's it all about?

Strott

Higashi

2003

Journal of Lipid Research

205

184

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Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g., protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity of serine proteases, e.g., those involved in blood clotting, fibrinolysis, and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation, inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to work out the molecular mechanisms whereby this interesting molecule carries out its various roles. -Strott, C. A., and Y. Higashi. Cholesterol sulfate in human physiology: what's it all about? J.

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The Binding of Androsterone Sulfate, Etiocholanolone Sulfate, and Dehydroisoandrosterone Sulfate by Human Plasma Protein*

Cited by 60 publications

References 12 publications

Binding of digitoxin and some related cardenolides to human plasma proteins

Binding of digitoxin and some related cardenolides to human plasma proteins

Estrone Sulfate: Production Rate and Metabolism in Man

Cholesterol sulfate in human physiology: what's it all about?

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