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At least 649 records · Page 36Linked to original sources
PubMed1989

Kinetic modeling of the recA protein promoted renaturation of complementary DNA strands.

Quantitative agarose gel assays reveal that the recA protein promoted renaturation of complementary DNA strands (phi X DNA) proceeds in two stages. The first stage results in the formation of unit-length duplex DNA as well as a distribution of other products ("initial products"). In the second stage, the initial products are converted to complex multipaired DNA structures ("network DNA"). In the presence of ATP, the initial products are formed within 2 min and are then rapidly converted to network DNA. In the absence of ATP, the initial products are formed nearly as fast as with ATP present, but they are converted to network DNA at a much lower rate. The time-dependent formation of initial products and network DNA from complementary single strands for both the ATP-stimulated and ATP-independent reactions can be modeled by using a simple two-step sequential kinetic scheme. This model indicates that the primary effect of ATP in the recA protein promoted renaturation reaction is not on the initial pairing step (which leads to the formation of initial products) but rather is to increase the rate at which subsequent pairing events can occur.

Adenosine Triphosphate↗
PubMed2002

Equilibrium and kinetic modeling of adsorption of reactive dye on cross-linked chitosan beads.

The adsorption of reactive dye (Reactive Red 189) from aqueous solutions on cross-linked chitosan beads was studied in a batch system. The equilibrium isotherms at different particle sizes (2.3-2.5, 2.5-2.7 and 3.5-3.8mm) and the kinetics of adsorption with respect to the initial dye concentration (4320, 5760 and 7286 g/m(3)), temperature (30, 40 and 50 degrees C), pH (1.0, 3.0, 6.0 and 9.0), and cross-linking ratio (cross-linking agent/chitosan weight ratio: 0.2, 0.5, 0.7 and 1.0) were investigated. Langmuir and Freundlich adsorption models were applied to describe the experimental isotherms and isotherm constants. Equilibrium data fitted very well to the Langmuir model in the entire saturation concentration range (0-1800 g/m(3)). The maximum monolayer adsorption capacities obtained from the Langmuir model are very large, which are 1936, 1686 and 1642 g/kg for small, mediumand large particle sizes, respectively, at pH 3.0, 30 degrees C, and the cross-linking ratio of 0.2. The pseudo first- and second-order kinetic models were used to describe the kinetic data, and the rate constants were evaluated. The experimental data fitted well to the second-order kinetic model, which indicates that the chemical sorption is the rate-limiting step, instead of mass transfer. The initial dye concentration and the solution pH both significantly affect the adsorption capacity, but the temperature and the cross-linking ratio are relatively minor factors. An increase in initial dye concentration results in the increase of adsorption capacity, which also increases with decreasing pH. The activation energy is 43.0 kJ/mol for the adsorption of the dye on the cross-linked chitosan beads at pH 3.0 and initial dye concentration 3768 g/m(3).

Adsorption↗
PubMed2004

Kinetic models of ion transport through a nanopore.

Kinetic equations for the stationary state distribution function of ions moving through narrow pores are solved for a number of 1D models of single ion transport. Ions move through pores of length L, under the action of a constant external field and of a concentration gradient. The interaction of single ions with the confining pore surface and with water molecules inside the pore are modeled by a Fokker-Planck term in the kinetic equation, or by uncorrelated collisions with thermalizing centers distributed along the pore. The temporary binding of ions to polar residues lining the pore is modeled by stopping traps or energy barriers. Analytic expressions for the stationary ion current through the pore are derived for several versions of the model, as functions of key physical parameters. In all cases, saturation of the current at high fields is predicted. Such simple models, for which results are analytic, may prove useful in the study of the current/voltage relations of ion channels through membranes.

Journal Article↗
PubMed2002

A kinetic model for enzyme interfacial activity and stability: pa-hydroxynitrile lyase at the diisopropyl ether/water interface.

A kinetic framework is developed to describe enzyme activity and stability in two-phase liquid-liquid systems. In particular, the model is applied to the enzymatic production of benzaldehyde from mandelonitrile by Prunus amygdalus hydroxynitrile lyase (pa-Hnl) adsorbed at the diisopropyl ether (DIPE)/aqueous buffer interface (pH = 5.5). We quantitatively describe our previously obtained experimental kinetic results (Hickel et al., 1999; 2001), and we successfully account for the aqueous-phase enzyme concentration dependence of product formation rates and the observed reaction rates at early times. Multilayer growth explains the early time reversibility of enzyme adsorption at the DIPE/buffer interface observed by both enzyme-activity and dynamic-interfacial-tension washout experiments that replace the aqueous enzyme solution with a buffer solution. The postulated explanation for the unusual stability of pa-Hnl adsorbed at the DIPE/buffer interface is attributed to a two-layer adsorption mechanism. In the first layer, slow conformational change from the native state leads to irreversible attachment and partial loss of catalytic activity. In the second layer, pa-Hnl is reversibly adsorbed without loss in catalytic activity. The measured catalytic activity is the combined effect of the deactivation kinetics of the first layer and of the adsorption kinetics of each layer. For the specific case of pa-Hnl adsorbed at the DIPE/buffer interface, this combined effect is nearly constant for several hours resulting in no apparent loss of catalytic activity. Our proposed kinetic model can be extended to other interfacially active enzymes and other organic solvents. Finally, we indicate how interfacial-tension lag times provide a powerful tool for rational solvent selection and enzyme engineering.

Adsorption↗
PubMed2005

Automatic network coupling analysis for dynamical systems based on detailed kinetic models.

We introduce a numerical complexity reduction method for the automatic identification and analysis of dynamic network decompositions in (bio)chemical kinetics based on error-controlled computation of a minimal model dimension represented by the number of (locally) active dynamical modes. Our algorithm exploits a generalized sensitivity analysis along state trajectories and subsequent singular value decomposition of sensitivity matrices for the identification of these dominant dynamical modes. It allows for a dynamic coupling analysis of (bio)chemical species in kinetic models that can be exploited for the piecewise computation of a minimal model on small time intervals and offers valuable functional insight into highly nonlinear reaction mechanisms and network dynamics. We present results for the identification of network decompositions in a simple oscillatory chemical reaction, time scale separation based model reduction in a Michaelis-Menten enzyme system and network decomposition of a detailed model for the oscillatory peroxidase-oxidase enzyme system.

Algorithms↗
PubMed2003

Accumulation of perchlorate in tobacco plants: development of a plant kinetic model.

Previous studies have shown that tobacco plants are tolerant of perchlorate and will accumulate perchlorate in plant tissues. This research determined the uptake, translocation, and accumulation of perchlorate in tobacco plants. Three hydroponics growth studies were completed under greenhouse conditions. Depletion of perchlorate in the hydroponics nutrient solution and accumulation of perchlorate in plant tissues were determined at two-day intervals using ion chromatography. Perchlorate primarily accumulated in tobacco leaves, yielding a substantial storage capacity for perchlorate. Mass balance results show that perchlorate degradation was negligible in plants. Tobacco plants were shown to effectively accumulate perchlorate over a wide range of initial concentrations (10 ppb to 100 ppm) from the hydroponics solution. Results suggest that plants are potential plants for the phytoremediation of perchlorate. A mathematical model was developed to describe the distribution of perchlorate in tobacco plants under rapid growth conditions. The Plant Kinetic (PK) model defined a plant as a set of compartments, described by mass balance differential equations and plant-specific physiological parameters. Data obtained from a separate hydroponics growth study with multiple solution perchlorate concentrations were used to validate predicted root, stem, and leaf concentrations. There was good agreement between model predictions and measured concentrations in the plant. The model, once adequately validated, can be applied to other terrestrial plants and inorganic chemicals currently used for both phytoremediation and ecological risk assessment.

Kinetics↗
PubMed1993

Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil.

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration (Bmax) and equilibrium dissociation constant (Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/k2 estimate of 0.68 +/- 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma (f1) was determined for each study (high SA f1: 0.50 +/- 0.03; low SA f1: 0.48 +/- 0.05). The free fraction in brain (f2) was calculated using the inhibition K1/k2 ratio and each volunteer's mean f1 value (f2 across volunteers = 0.72 +/- 0.03 ml/ml). Three methods (Methods I-III) were examined. Method I determined five kinetic parameters simultaneously [K1, k2, k3 (= konf2Bmax), k4, and konf2/SA] with no priori constraints. An average kon value of 0.030 +/- 0.003 nM-1 min-1 was estimated for receptor-rich regions using Method I. In Methods II and III, the konf2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/mumol). Four parameters were determined simultaneously using Method II. In Method III, K1/k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 +/- 25 nM in the occipital cortex, 64 +/- 18 nM in the cerebellum, and 38 +/- 5.5 nM in the thalamus; the average Kd was 8.9 +/- 1.0 nM (five brain regions).

Adult↗
PubMed2001

A kinetic model to evaluate cholesterol efflux from THP-1 macrophages to apolipoprotein A-1.

The kinetics (0 to 3 h) of cholesterol efflux to delipidated apolipoprotein A-1 were investigated, and the experimental data were best fitted to a mathematical model that involves two independent pathways of cholesterol efflux. The first pathway with a rate constant of 4.6 h(-1) is fast but removes only 3-5% of total cholesterol. After preconditioning apoA-1, it was found that this pathway remains, and hence it is a property of the cholesterol-loaded cells rather than due to modification on the apolipoprotein. This fast initial efflux does not seem to contribute to cholesterol efflux at later stages (>1 h) where a second pathway predominates. However, the fast initial efflux pool can be restored if apoA-1 is withdrawn. The second slower pathway (k(membrane--media) = 0.79 h(-1)) is associated with cholesterol ester hydrolysis whose rate constant could be experimentally verified (k(cal) = 0.43, k(exp) = 0.38 +/- 0.05). The model suggests that two different plasma membrane domains are involved in the two pathways. Loading of the cells with an oxysterol, 7-ketocholesterol (7K), inhibits efflux from both pathways. The model predicts that 7K decreases the initial efflux by decreasing the available cholesterol (by possibly affecting lipid packing), while all rate constants in the second pathway are decreased. In conclusion, the kinetic model suggests that cholesterol efflux to apoA-1 is a two-step process. In the first step, some of the plasma membrane cholesterol contributes to a fast initial efflux (possibly from lipid rafts) and leads to a second pathway that mobilizes intracellular cholesterol mobilization.

Acetylation↗
PubMed1999

A kinetic model of the transient phase in the response of olfactory receptor neurons.

A model is presented that predicts the instantaneous spike rate of an olfactory receptor neuron (ORN) in response to the quality and concentration of an odor stimulus. The model accounts for the chemical kinetics of ligand-receptor binding and activation processes, and implicitly the initiation of second messenger cascades that lead to depolarization and/or hyperpolarization of the ORN membrane. Both of these polarizing processes are included in the most general form of the model, as well as a process that restores the voltage to its negative resting state. The spike rate is assumed to be linearly proportional to the level of voltage depolarization above a critical negative voltage level. The model includes the simplifying assumption that activation of bound ligand-receptor complexes by G-proteins and other enabling molecules follows a Monod function that has the ratio of enabling molecules to bound unactivated ligand-receptor complexes as its argument. Parameters are selected that provide an excellent fit of the model to previously published empirical data on the response of cockroach ORNs to pulsed 1-hexanol stimuli. The sensitivity of model output to various model parameters is investigated and changes to parameters are discussed that would improve the ability of ORNs to follow rapidly pulsed stimuli.

Action Potentials↗
PubMed1993

Kinetic modelling and underdialysis in CAPD patients.

Kinetic analysis was performed in all 58 patients undergoing standard CAPD. The urea distribution volume was estimated from anthropomorphic measurements (Watson formulae). Normalized protein catabolic rate (NPCR), daily protein leak (PL), urea and creatinine Kt/Vs, clearances and peritoneal mass transfer coefficients (Kp) were calculated from measurements on serum, 24-h urine and PD fluid effluent. The mean total (renal+PD) daily creatinine and urea Kt/Vs (KT/V) were 0.31 (range 0.15-0.79) and 0.31 (0.18-0.65). There was no relationship between KT/V and serum urea or Kp. The strongest determinant of the urea KT/V was the residual renal urea clearance (KrU)(R = 0.79, P < 0.001) which decreased with time on dialysis (R = -0.38, P < 0.005). There was a significant correlation between the hospital admissions per year and both the urea and creatinine KT/V and KrU (R = -0.30, -0.32, P < 0.05). Patients with urea KT/V < 0.25 (n = 22) had more hospital admissions/year than those with KT/V > 0.25 (mean of 2.6 versus 1.5, P < 0.05). NPCR correlated with urea KT/V (R = 0.62, P < 0.001) but not with serum albumin or the PL. Patients identified by UKM to be less well dialysed have a lower residual renal function and are more likely to be hospitalized. Undernutrition in CAPD patients appears to be related to underdialysis rather than protein loss.

Creatinine↗
PubMed1992

Analysis of a kinetic model for melanin biosynthesis pathway.

The kinetic behavior of the melanin biosynthesis pathway from L-tyrosine up to dopachrome has been studied from experimental and simulation assays. The reaction mechanism proposed is based on a single active site of tyrosinase. The diphenolase and monophenolase activities of tyrosinase involve one single (oxidase) and two overlapped (hydroxylase and oxidase) catalytic cycles, respectively. The stoichiometry of the pathway implies that one molecule of tyrosinase must accomplish two turnovers in the hydroxylase cycle for each one in the oxidase cycle. Furthermore, the steady-state rates of dopachrome production and O2 consumption from tyrosine and L-dopa, also fulfill the stoichiometry of the pathway: VO2T/VDCT = 1.5 and VO2T/VDCD = 1.0, where T represents L-tyrosine, DC represents dopachrome, and D represents L-dopa. It has been ascertained by high performance liquid chromatography that in the steady-state, a quantity of dopa is accumulated ([D]ss) which fulfills the constant ratio [D]ss = R[T]0. Taking this ratio into account, an analytical expression has been deduced for the monophenolase activity of tyrosinase. In this expression kcatT congruent to (2/3)k3(K1/K2)R, revealing that kcatT is not a true catalytic constant, since it also depends on equilibrium constants and on the experimental R = 0.057. This low value explains the lower catalytic efficiency of tyrosinase on tyrosine than on dopa, (VmaxT/KmT)/(VmaxD/KmD) congruent to (2/3)R, since a significant portion of tyrosinase is scavenged from the catalytic turnover as dead-end complex EmetT in the steady-state of the monophenolase activity of tyrosinase.

Basidiomycota↗
PubMed2001

Analysis of an internal kinetic model for free and bound tritium.

Internal dosimetry models that currently drive regulatory compliance decisions assume that tritium retention kinetic behavior can be modeled by a single exponential function. This is contrary to the results of a number of modeling techniques, which indicate that while elemental tritium (HT) and tritiated water (HTO) are the most commonly released forms of tritium, organically-bound tritium (OBT) doses can be quite significant. In this paper, a unified two-compartment model of the retention kinetics of HTO and OBT is examined for the purpose of investigating the importance of metabolic routes not considered in the ICRP one- and two-exponent models; namely the transfer of tritium from the HTO compartment to the OBT compartment and vice versa. In particular, the effect of intake ratio is investigated, and a detailed analysis of dosimetric implications is performed. For typical combined intakes of HTO and OBT, the number of disintegrations from the two tritium forms can be roughly equal. This result, when combined with the suggested greater biological effectiveness of OBT, indicates effective doses will be greater than those obtained from a single exponential model. The results of this study corroborate previous findings using the two-compartment model for the cases of HTO-only and or OBT-only intakes and compare well with data taken from studies on animals and human subjects.

Adult↗
PubMed2002

A two-state kinetic model for the unfolding of single molecules by mechanical force.

We investigate the work dissipated during the irreversible unfolding of single molecules by mechanical force, using the simplest model necessary to represent experimental data. The model consists of two levels (folded and unfolded states) separated by an intermediate barrier. We compute the probability distribution for the dissipated work and give analytical expressions for the average and variance of the distribution. To first order, the amount of dissipated work is directly proportional to the rate of application of force (the loading rate) and to the relaxation time of the molecule. The model yields estimates for parameters that characterize the unfolding kinetics under force in agreement with those obtained in recent experimental results. We obtain a general equation for the minimum number of repeated experiments needed to obtain an equilibrium free energy, to within k(B)T, from nonequilibrium experiments by using the Jarzynski formula. The number of irreversible experiments grows exponentially with the ratio of the average dissipated work, W(dis) to k(B)T.

Biomechanical Phenomena↗
PubMed2002

Simulation of trichloroacetic acid kinetics in the isolated perfused rat liver using a biologically based kinetic model.

Trichloroacetic acid (TCA) is a contaminant of drinking water. It induces peroxisome proliferation in livers of rats and mice and is hepatocarcinogenic in the latter species. Previous experimental studies of the kinetics of TCA in the isolated perfused rat liver (IPRL) at two doses have been reported. To gain more insight into the mechanistic processes controlling TCA kinetics in the liver a biologically based kinetic (BBK) model for the IPRL was used to analyze the experimental data. The IPRL was exposed to 25, 250, or 1000 microM TCA for 2 h in a recirculating perfusion system. These doses were not cytotoxic. The BBK model simulated the TCA concentration in perfusion medium and liver, and the biliary excretion of TCA. Separate protein binding studies showed that over 90% of TCA was bound to albumin in the perfusion medium whereas binding in liver homogenate was much lower. Integrating the information on protein binding into the BBK model, the hepatic uptake of TCA and its biliary excretion could be fitted assuming asymmetrical saturable transport at the sinusoidal membrane and linear transport at the bile canalicular membrane. To validate the BBK model, additional washout experiments were conducted in which the perfusion medium was replaced with TCA-free medium after 30 min of exposure of the liver to 1000 microM TCA. This approach illustrates the usefulness of BBK modeling for analyzing experimental kinetic data and gaining insight in kinetic mechanisms controlling the behavior of a chemical in the liver.

Animals↗
PubMed2006

Metal speciation in sulphidic sediments: a new method based on oxidation kinetics modelling in the presence of EDTA.

The solid phase partitioning of metals (Zn, Cu and Pb) was determined in four anoxic, metal polluted sediments by investigating at pH 8 the 1 day oxidation kinetics of the metal sulphide phases present in the sediments in a background solution containing excess EDTA. A mathematical model consisting of a combination of two pseudo-first order reactions was used to fit the metal release data as a function of oxidation time. The model permitted to fractionate the trace metals in a 'quickly-oxidizable' and a 'slowly-oxidizable' fraction, which could be assigned to two different trace metal pools, respectively (1) FeS minerals (e.g. amorphous FeS, mackinawite) and (2) discrete trace metal sulphide phases. The sum of the fractions associated with these sulphide pools was taken as an approximation for the sulphide-associated fraction of the trace metals and coincided (for the case of Zn and Pb) with the sulphide-associated fraction derived from the analysis of acid volatile sulphide (AVS) and simultaneously extracted metals (SEM). Oxidation kinetics modelling allowed also determining the sulphide-associated fraction of a broad range of trace metals (as demonstrated for Cu) more accurately than the AVS/SEM method, which suffers from non-efficient extraction of a number of trace metal sulphides. A correction was made for the determination of the sulphide-associated fraction by subtracting the trace metal fraction dissolved after 1 day under anoxic conditions in the background EDTA solution. The combination of (1) one day oxidation kinetics modelling and (2) correction for the 1 day anoxic EDTA-soluble fraction is a suitable method to determine accurately the true sulphide speciation of trace metals in anoxic sediments.

Edetic Acid↗
PubMed1999

Kinetic modeling of slow dissociation of bromosulphophthalein from albumin in perfused rat liver: toxicological implications.

Due to strong binding between organic anions and albumin, the kinetics of the binding process must be carefully considered in biologically-based models used for predictive toxicology applications. Specifically, the slow dissociation rate of an organic anion from the protein may lead to reduced availability of free anion in its flow through the capillaries of an organ. In this work, the effect of the dissociation rate of the anion bromosulphophthalein (BSP) from albumin was studied in isolated, perfused rat livers in the presence of albumin concentrations of 0.25, 1, and 4% (w/v) and an initial BSP concentration of 20 microM. The uptake of BSP from the perfusion medium was modeled using a biologically-based kinetic model of the sinusoidal and intracellular liver compartments. The best fit of the model to data resulted in the prediction of a slow dissociation rate constant for the BSP-albumin of between 0.097 and 0.133 s(-1). Assuming BSP and albumin to be in binding equilibrium in the sinusoidal space, with rapid binding-rate constants, as is often done, produced an unacceptable fit. These results indicate that the strong binding interaction between BSP and albumin, beyond keeping the concentration of free chemical low due to a small equilibrium dissociation constant, can also reduce uptake by an organ due to the slow release of BSP from the protein during passage through the capillaries. The implication of this dissociation-limited condition, when extrapolating to other doses and in-vivo situations, is discussed.

Animals↗
PubMed1986

Reaction sequences for (Na+ + K+)-dependent ATPase hydrolytic activities: new quantitative kinetic models.

To delineate better the reaction sequence of the (Na+ + K+)-ATPase and illuminate properties of the active site, kinetic data were fitted to specific quantitative models. For the (Na+ + K+)-ATPase reaction, double-reciprocal plots of velocity against ATP (in the millimolar range), with a series of fixed KCl concentrations, are nearly parallel, in accord with the ping pong kinetics of ATP binding at the low-affinity sites only after Pi release. However, contrary to requirements of usual formulations, Pi is not a competitor toward ATP. A new steady-state kinetic model accommodates these data quantitatively, requiring that under usual assay conditions most of the enzyme activity follows a sequence in which ATP adds after Pi release, but also requiring a minor alternative pathway with ATP adding after K+ binds but before Pi release. The fit to the data also reveals that Pi binds nearly as rapidly to E2 X K X ATP as to E2 X K, whereas ATP binds quite slowly to E2 X P X K: the site resembles a cul-de-sac with distal ATP and proximal Pi sites. For the K+-nitrophenyl phosphatase reaction also catalyzed by this enzyme, the apparent affinities for both substrate and Pi (as inhibitor) decrease with higher KCl concentrations, and both Pi and TNP-ATP appear to be competitive inhibitors toward substrate with 10 mM KCl but noncompetitive inhibitors with 1 mM KCl. These data are accommodated quantitatively by a steady-state model allowing cyclic hydrolytic activity without obligatory release of K+, and with exclusive binding of substrate vs. either Pi or TNP-ATP. The greater sensitivity of the phosphatase reaction to both Pi and arsenate is attributable to the weaker binding by the occluded-K+ enzyme form occurring in the (Na+ + K+)-ATPase reaction sequence. The steady-state models are consistent with cyclical interconversion of high- and low-affinity substrate sites accompanying E1/E2 transitions, with distortion to low-affinity sites altering not only affinity and route of access but also separating the adenine- and phosphate-binding regions, the latter serving in the E2 conformation as the active site for the phosphatase reaction.

Animals↗