In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant

2016 ◽  
Vol 37 (10) ◽  
pp. 831-842 ◽  
Author(s):  
Wilhelmus E.A. de Witte ◽  
Meindert Danhof ◽  
Piet H. van der Graaf ◽  
Elizabeth C.M. de Lange
Keyword(s):  
Residence Time ◽  
Rate Constant ◽  
Association Rate Constant ◽  
Association Rate ◽  
Kinetic Selectivity

Velocity of O2 uptake by human red blood cells

1961 ◽  
Vol 16 (3) ◽  
pp. 511-516 ◽  
Author(s):  
N. C. Staub ◽  
J. M. Bishop ◽  
R. E. Forster
Keyword(s):  
Rate Constant ◽  
Intermediate Compound ◽  
Oxygen Electrode ◽  
Theoretical Explanation ◽  
Association Rate Constant ◽  
Association Rate ◽  
Human Red Blood Cells ◽  
Hemoglobin Saturation ◽  
Uptake Process ◽  
Normal Human

We have determined the over-all association rate constant, k'c, for the uptake of oxygen by normal human erythrocytes from 0% to 97% initial hemoglobin saturation at pH 7.4 and 37óC. With a modified Hartridge-Roughton rapid-reaction apparatus, we used a small oxygen electrode to follow the oxygen uptake process rather than using the usual photocolorimetric analytical methods. The value of k'c averages 164 mm-1 sec.-1 at 0% initial saturation, rises slowly to over 300 at 50%, and then climbs rapidly to over 1500 at 95%. The theoretical explanation for the increase in k-c with rising initial oxyhemoglobin saturation is based on the increasing prominence of the fourth chemical association rate constant, k-4, in the intermediate compound theory of Adair. It is known that k-4 is several times larger than any of the other three k–s. Submitted on December 19, 1960

The Association Rate Constant for Heme Binding to Globin Is Independent of Protein Structure†

Biochemistry ◽  
1996 ◽  
Vol 35 (35) ◽  
pp. 11293-11299 ◽  
Author(s):  
Mark S. Hargrove ◽  
Doug Barrick ◽  
John S. Olson
Keyword(s):  
Protein Structure ◽  
Rate Constant ◽  
Heme Binding ◽  
Association Rate Constant ◽  
Association Rate

scholarly journals Effect of sodium on amiloride- and triamterene-induced current fluctuations in isolated frog skin.

1986 ◽  
Vol 87 (3) ◽  
pp. 425-442 ◽  
Author(s):  
T Hoshiko ◽  
W Van Driessche
Keyword(s):  
Rate Constant ◽  
Frog Skin ◽  
Rana Temporaria ◽  
Rana Esculenta ◽  
Inhibitory Effect ◽  
Corner Frequency ◽  
Bathing Solution ◽  
Association Rate Constant ◽  
Association Rate ◽  
Three State Model

The apparent association constants of two agents, amiloride and triamterene, that block the Na-selective channel of apical membrane of frog skin are shown to decrease as the Na concentration is increased in the apical bathing solution in isolated skin of the frog, Rana temporaria, Rana esculenta, and Rana pipiens. These results were obtained in "normally polarized" skins. These effects were independent of the anion used (chloride or methylsulfate) or the cation used as the Na substitute (Tris, DDA, or K ion). When NaCl was replaced with mannitol, the Na effect on the amiloride association rate constant persisted, which shows that ionic strength was not critically involved. The amiloride corner frequency was unaffected when the clamp potential was altered from +100 to -60 mV. The Na dependence was greatly attenuated or absent when the serosal surface was bathed in 120 mM K Ringer's, an effect that appears to be attributable to some pharmacological effect of high serosal K. A previously described three-state model is used to analyze the inhibitory effect of Na on the blocker association rate constant.

Kinetic aspects of structure─activity relations: the binding of sulphonamides by carbonic anhydrase

1976 ◽  
Vol 193 (1111) ◽  
pp. 107-125 ◽  
Keyword(s):  
Carbonic Anhydrase ◽  
Rate Constant ◽  
Homologous Series ◽  
Complex Structure ◽  
Association Rate Constant ◽  
Association Rate ◽  
Fast Kinetics ◽  
Binding Process ◽  
Structure Activity ◽  
Structure Activity Relations

The fast kinetics of binding of sulphonamides to carbonic anhydrase have been examined. Six homologous series of sulphonamides have been studied. In all cases the increase in binding constant in a homologous series is due mainly to an increase in the association rate constant. Meta- and ortho-substituted sulphonamides have lower binding constants also mainly due to a lower association rate constant. The binding of sulphonamides to apocarbonic anhydrase has been measured by a specific affinity method. The effects of homologous series are largely reproduced on the apoenzyme but the effects of positional isomerization are not; the binding process is pH-insensitive. Evidence is presented that the binding process for sulphonamides and carbonic anhydrase involves an intermediate non-coordinate complex which is then converted into the final coordinate complex. Structure-activity relations in the binding of sulphonamides to carbonic anhydrase are examined on the basis of effects on ( a ) the stability of the intermediate complex; ( b ) the rate of isomerization into the coordinate complex; ( c ) the dissociation rate constant.

scholarly journals The rates of formation and dissociation of actin-myosin complexes. Effects of solvent, temperature, nucleotide binding and head-head interactions

1982 ◽  
Vol 203 (2) ◽  
pp. 453-460 ◽  
Author(s):  
S B Marston
Keyword(s):  
Rate Constant ◽  
Protein Concentration ◽  
Order Rate Constant ◽  
Dissociation Rate ◽  
Dissociation Rate Constant ◽  
Light Scatter ◽  
Association Rate Constant ◽  
Heavy Meromyosin ◽  
Association Rate ◽  
Low Protein

The rates of formation and dissociation of actin-subfragment 1 and actin-heavy mero-myosin complexes were measured by using light-scatter and the change in fluorescence of N-iodoacetyl-N'-(5-sulpho-1-naphthyl)ethylenediamine (IAEDANS)-labelled acting as probes. Association rate measurements were made at low protein concentration, where the transients approximated to single exponentials with rate constants proportional to the concentration of reactant in excess. Dissociation rate measurements were made by displacing IAEDANS-actin from myosin with excess native actin and by a salt jump. The second-order rate constant of association for actin-subfragment 1 was 3 × 10(6) M-1 . s-1 in 60 mM-KCl at 13 degree C. It was decreased 10-fold in 500 mM-KCl and in 50% (v/v) glycol. It was decreased 6-fold when MgADP or Mg[beta gamma-imido]ATP bound to myosin. The dissociation rate constant was 0.012 s-1 in 60 mM-KCl at 13 degree C. It was increased 4-fold by 500 mM-KCl, 25-fold by 50% glycol, 8-fold by MgADP binding and 170-fold by Mg[beta gamma-imido]ATP binding. Ea for association was 70 kJ . mol-1 and for dissociation 35 kJ . mol-1. Heavy meromyosin associated at twice the rate observed for subfragment 1 and dissociated at less than one-twentieth of the rate for subfragment 1 (60 mM-KCl, 25 degree C), but when Mg[beta gamma-imido]ATP bound actin-heavy meromyosin dissociated at one-half the rate for subfragment 1. There were significant correlations between increase in the dissociation rate constant, decrease in binding constant and increase in magnitude of conformational change. The association rate constant did not correlate with any property of the actin-myosin complex.

Aeronomic importance of ion–molecule clustering reactions

1969 ◽  
Vol 47 (10) ◽  
pp. 1809-1811 ◽  
Author(s):  
D. K. Bohme
Keyword(s):  
Temperature Dependence ◽  
Rate Constant ◽  
Literature Survey ◽  
Empirical Correlation ◽  
Experimental Measurements ◽  
Association Rate Constant ◽  
Association Rate ◽  
Mass Spectrometers ◽  
Ion Clusters ◽  
Altitude Profile

A literature survey of observations of ion clusters in mass spectrometers indicates that the association rate constant depends on the number of atoms in the cluster. An altitude profile of estimated apparent bimolecular rates of clustering in the atmosphere is made from this empirical correlation. Experimental measurements of the termolecular rate constant for clusters in formation are reported; the temperature dependence of some of these has been measured.

scholarly journals Hemoglobin in Frankia, a Nitrogen-Fixing Actinomycete

2002 ◽  
Vol 68 (5) ◽  
pp. 2629-2631 ◽  
Author(s):  
John D. Tjepkema ◽  
Robert E. Cashon ◽  
Jason Beckwith ◽  
Christa R. Schwintzer
Keyword(s):  
Optical Absorption ◽  
Rate Constant ◽  
Dissociation Rate ◽  
Oxygen Binding ◽  
Association Rate Constant ◽  
Association Rate ◽  
Absorption Bands ◽  
Oxygen Dissociation ◽  
Equilibrium Oxygen ◽  
Strain Cci3

ABSTRACT Frankia strain CcI3 grown in culture produced a hemoglobin which had optical absorption bands typical of a hemoglobin and a molecular mass of 14.1 kDa. Its equilibrium oxygen binding constant was 274 nM, the oxygen dissociation rate constant was 56 s−1, and the oxygen association rate constant was 206 μM−1 s−1.

scholarly journals Phalloidin enhances actin assembly by preventing monomer dissociation.

1984 ◽  
Vol 99 (2) ◽  
pp. 529-535 ◽  
Author(s):  
L M Coluccio ◽  
L G Tilney
Keyword(s):  
Rate Constant ◽  
Actin Filaments ◽  
Critical Concentration ◽  
Dissociation Rate ◽  
Dissociation Rate Constant ◽  
Muscle Actin ◽  
Actin Assembly ◽  
Association Rate Constant ◽  
Association Rate ◽  
Dissociation Rate Constants

Incubation of the isolated acrosomal bundles of Limulus sperm with skeletal muscle actin results in assembly of actin onto both ends of the bundles. These cross-linked bundles of actin filaments taper, thus allowing one to distinguish directly the preferred end for actin assembly from the nonpreferred end; the preferred end is thinner. Incubation with actin in the presence of equimolar phalloidin in 100 mM KCl, 1 mM MgCl2 and 0.5 mM ATP at pH 7.5 resulted in a slightly smaller association rate constant at the preferred end than in the absence of the drug (3.36 +/- 0.14 X 10(6) M-1 s-1 vs. 2.63 +/- 0.22 X 10(6) M-1 s-1, control vs. experimental). In the presence of phalloidin, the dissociation rate constant at the preferred end was reduced from 0.317 +/- 0.097 s-1 to essentially zero. Consequently, the critical concentration at the preferred end dropped from 0.10 microM to zero in the presence of the drug. There was no detectable change in the rate constant of association at the nonpreferred end in the presence of phalloidin (0.256 +/- 0.015 X 10(6) M-1 s-1 vs. 0.256 +/- 0.043 X 10(6) M-1 s-1, control vs. experimental); however, the dissociation rate constant was reduced from 0.269 +/- 0.043 s-1 to essentially zero. Thus, the critical concentration at the nonpreferred end changed from 1.02 microM to zero in the presence of phalloidin. Dilution-induced depolymerization at both the preferred and nonpreferred ends was prevented in the presence of phalloidin. Thus, phalloidin enhances actin assembly by lowering the critical concentration at both ends of actin filaments, a consequence of reducing the dissociation rate constants at each end.

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