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At least 613 records · Page 34Linked to original sources
PubMed2006

Kinetic modeling and fitting software for interconnected reaction schemes: VisKin.

Reaction kinetics for complex, highly interconnected kinetic schemes are modeled using analytical solutions to a system of ordinary differential equations. The algorithm employs standard linear algebra methods that are implemented using MatLab functions in a Visual Basic interface. A graphical user interface for simple entry of reaction schemes facilitates comparison of a variety of reaction schemes. To ensure microscopic balance, graph theory algorithms are used to determine violations of thermodynamic cycle constraints. Analytical solutions based on linear differential equations result in fast comparisons of first order kinetic rates and amplitudes as a function of changing ligand concentrations. For analysis of higher order kinetics, we also implemented a solution using numerical integration. To determine rate constants from experimental data, fitting algorithms that adjust rate constants to fit the model to imported data were implemented using the Levenberg-Marquardt algorithm or using Broyden-Fletcher-Goldfarb-Shanno methods. We have included the ability to carry out global fitting of data sets obtained at varying ligand concentrations. These tools are combined in a single package, which we have dubbed VisKin, to guide and analyze kinetic experiments. The software is available online for use on PCs.

Computer Simulation↗
PubMed2002

Effect of algal extract on H2 production by a photosynthetic bacterium Rhodobium marinum A-501: analysis of stimulating effect using a kinetic model.

We have established a system for hydrogen (H2) production from algal starch via lactic acid using a mixed culture of a lactic acid bacterium, Lactobacillus amylovorus, and a photosynthetic bacterium, Rhodobium marinum A-501. We found that the H2 production from lactate was stimulated in the presence of algal extract, which was obtained from algal biomass homogenate used as a substrate in the system by removing settleable solids including starch. To analyze the stimulating effect of algal extract on H2 production, we developed a kinetic model for H2 production by R. marinum A-501. The model revealed that approximately 20% of lactate was consumed for cell mass production, and the remaining portion was a source of reducing power to drive hydrogen production or other cellular processes. In the presence of algal extract, the model indicated that the conversion efficiency from lactate to the reducing power increased from 0.56 to 0.80 and nitrogenase activity increased up to twofold, resulting in the increase in yield of hydrogen from lactate from 29% to 48%. These results suggest that algal extract can attenuate the limitation process in lactate catabolism by which the supplementation of reducing power to drive H2 production was suppressed.

Journal Article↗
PubMed1996

How profilin/barbed-end synergy controls actin polymerization: a kinetic model of the ATP hydrolysis circuit.

The role of ATP hydrolysis in the regulation of the actin cytoskeleton continues to be a subject of controversy. Since actin polymerization can occur in the absence of ATP, the energy of hydrolysis is not needed for filament assembly. Recent work has instead suggested a regulatory role for ATP in cytoskeletal remodeling. In particular, both profilin and free filament barbed ends have been shown to play major roles in the processing of ATP by actin. We have developed a new integrated kinetic model to examine how the maintenance of the pool of unpolymerized actin and the flux of actin subunits through filaments are controlled by profilin and free filament barbed ends through their interaction with ATP. An analysis of the model's steady states predicts how two novel regulatory pathways may regulate the cytoskeleton in vivo. Coordinated changes in the availability of both profilin and free barbed ends mediate the following regulatory effects: (1) both the nucleotide composition and the absolute amount of free G-actin can be changed separately or together to substantially alter the total amount of F-actin; and (2) uncapping the barbed ends of only a modest fraction of filaments causes all filaments to begin slowly depolymerizing from their pointed ends, resulting in the total depolymerization of the remaining capped filaments. We report that the phenomenon of treadmilling, wherein the barbed end growth of each filament is exactly balanced by pointed end loss at steady state, is only possible in the limiting case when all barbed ends are uncapped. The capping of any fraction of barbed ends increases the critical concentration of ATP-G-actin, causing the remaining free barbed ends to grow faster than their pointed ends can shrink. On the basis of these findings we propose a major revision to the treadmilling model for actin-based motility, in which the rapidly growing filaments with free barbed ends are continuously severed toward their rear followed by capping of the newly exposed barbed ends. This revised model, herein referred to as "treadsevering," allows sustained and rapid barbed end growth to occur indefinitely at a steady state provided a continuous input of ATP.

Actins↗
PubMed2005

Kinetic model for the chiral symmetry breaking transition in the growth front of a conglomerate crystal phase.

In its molten phase, 1,1'-binaphthyl is racemic due to its high racemization rate, but it can crystallize as a conglomerate of R and S crystals. Our experiments have indicated that, under some conditions, the crystal growth front of 1,1'-binaphthyl shows many of the characteristics of an open system in which chiral symmetry is broken; i.e., the growing solid phase becomes predominantly R or S. Here we present a kinetic model to explain the observed chiral symmetry breaking. The model is based on growth due to attachment of R or S growth units to a crystal surface in a supercooled melt. Chiral symmetry breaking occurs due to chirally autocatalytic formation of R or S growth units on the growth surface. Unlike the many models suggested and studied in the 1980s, there is no cross-inhibition between R- and S-enantiomer in the model presented here. In our model, asymmetric and symmetric steady-state solutions that do not intersect were found. Through linear stability analysis, the critical point, at which a symmetric solution becomes unstable and makes a transition to an asymmetric solution, is determined.

Journal Article↗
PubMed2004

A kinetic model for Xylella fastidiosa adhesion, biofilm formation, and virulence.

Xylella fastidiosa is the causal agent of citrus variegated chlorosis and Pierce's disease which are the major threat to the citrus and wine industries. The most accepted hypothesis for Xf diseases affirms that it is a vascular occlusion caused by bacterial biofilm, embedded in an extracellular translucent matrix that was deduced to be the exopolysaccharide fastidian. Fourier transform infrared spectroscopy analysis demonstrated that virulent cells which form biofilm on glass have low fastidian content similar to the weak virulent ones. This indicates that high amounts of fastidian are not necessary for adhesion. In this paper we propose a kinetic model for X. fastidiosa adhesion, biofilm formation, and virulence based on electrostatic attraction between bacterial surface proteins and xylem walls. Fastidian is involved in final biofilm formation and cation sequestration in dilute sap.

Bacterial Adhesion↗
PubMed1983

Dose-response study of N-nitrosoproline formation in rats and a deduced kinetic model for predicting carcinogenic effects caused by endogenous nitrosation.

A dose-response study on the endogenous formation of N-nitrosoproline in rats was carried out by feeding various doses of L-proline in the diet and sodium nitrite in the drinking water. N-Nitrosoproline excreted in the urine and feces of individual rats was monitored as an index for endogenous nitrosation of proline. The logarithm of the amount of N-nitrosoproline formed was found to be proportional to the logarithm of the product of the proline dose and the square of the nitrite dose, in agreement with in vitro studies. On the basis of these results, a kinetic model was formulated. Calculations were carried out with this model using published data on nitrosation and carcinogenic potency of selected N-nitrosamines. This allowed the estimation of the daily precursor dose quantity, [amine][nitrite]2, required to give 50% tumor incidence in rats after 2 years of feeding.

Animals↗
PubMed1998

A preliminary cell kinetics model of thrombocytopenia after radioimmunotherapy.

UNLABELLED: Thrombocytopenia is often the dose-limiting toxicity for radionuclide therapy. Prediction of platelet counts after therapy is important for treatment planning. Simple prediction methods based on linear correlation between radiation dose and blood count nadir have been insufficient because they have not considered time, because of the complicated hierarchical structure of the hematopoietic system in which platelets are not directly injured by low dose rate radiation and because of changing radiation dose rates to marrow with time. This study addresses these problems using a cell kinetics model. METHODS: The model consists of compartments for progenitor cells, megakaryocytes, platelets and stromal cells. A linear quadratic formula was used for progenitor cell survival. Stromal cells were described by a model based on a maximum likelihood estimate for cellular damage, repair and proliferation. Reported values for murine cellular turnover rates and radiosensitivity of progenitor cells were used in the model calculations. Experimental mice received 4 Gy of external beam radiation for tumor implantation and 12.4-23.3 MBq 67Cu-2-iminothiolane-BAT-Lym-1 (BAT = 6-[p-(bromoacetamido) benzyl]-1,4,8,11-tetra-azacyclotetradecane-N,N',N'',N'''-tetraacet ic acid) 19-30 days later. Blood counts were measured three times each week. RESULTS: The model predicted the severity of thrombocytopenia, and the time of the nadir corresponded to measured values in mice. For a dose of 14.2 MBq 67Cu-2-iminothiolane-BAT-Lym-1 that induced a platelet nadir of 20% of baseline (Grade II), the model predicted that at least 20 days were needed before a second 14.2-MBq injection if a subsequent nadir of <10% of baseline (Grade IV) was to be avoided. CONCLUSION: The nadir and duration of thrombocytopenia predicted by the model were similar to those observed in the mice. Predicted information could be useful for planning the dose and timing of fractionated radionuclide therapy. This model provides a stepping stone for future development of a predictive model for patients.

Animals↗
PubMed2006

Chemical discrimination by a kinetic model of organic photooxidation in a heterosupramolecular assembly.

The photooxidation of range of common organic pollutants in a dye-sensitised photoelectrochemical cell (DS-PEC) is reported. A photoanode was prepared by the chemisorption of a photosensitiser, cis-bis-(2,2)-bipyridine)-(4,4'-bis-(methyl)phosphonato-2,2'-bipyridine)ruthenium(II) dichloride ([Ru(bpy)2(dmpbpy]2+), to a nanoporous nanocrystalline TiO2 thin film on a conducting glass substrate. The photoanode was coupled to a platinum electroplated fluorine doped tin oxide glass substrate in a two electrode assembly and the cell cavity was filled with an aqueous solution of organic pollutants and irradiated with lambda>420 nm to give a measurable photocurrent. In addition to the ability of this cell to photooxidise a range of chemically diverse organic pollutants, the application of a kinetic model to observed photocurrent transients allowed the study of interfacial electron transfer processes. Through the mathematical fit of a five-parameter double exponential decay function, evidence to support numerous interfacial reactions for the oxidation process were identified. Rapid oxidation of species in close proximity to the photooxidation centre was proposed as the kinetically fast interfacial process with a first-order rate constant of the order 0.4 s(-1). The slower process was attributed to the diffusion of oxidisable species from the solution bulk to the surface prior to oxidation with a first-order rate constant of the order 0.01 s(-1). Theoretical profiling of the kinetic events supported the biphasic assignment of interfacial processes and indicated that non-exhaustive oxidation occurs for the solution concentrations examined.

Journal Article↗
PubMedDate not supplied

Determination of extra renal clearance and generation rate of beta2-microglobulin in hemodialysis patients using a kinetic model.

Beta-2-microglobulin (beta2-m) has been proposed as a marker of middle molecules to assess one aspect of the efficacy of dialysis. Until now, few data have been published about extra renal (metabolic) clearance and generation rates of beta2-microglobulin, which are necessary for calculation of total clearance and mass removal of beta2-m in hemodialysis patients. We have developed a simple method to derive extra renal clearance and generation rates of beta2-m by measuring the pre and post dialysis blood concentrations of beta2-m using kinetic modeling. Ten stable hemodialysis patients were included in this study. Pre and post dialysis concentrations of beta2-m were measured during dialysis with low flux dialyzers (F6 HPS) and after 10 days switching to high flux dialyzers (F60S or Superflux). With a validated two pool model, the generation rate of beta2-m can be determined if extra renal clearance is known. Assuming the generation rate of beta2-m to be constant in each patient, the computer reiterated the calculation of extra renal clearance until the calculated generation rate was equal for both the low flux and the high flux dialyzer. Extra renal clearance was found to be between 1.97 and 4.11 ml/min (average, 3.2 ml/min). Generation rate was found in a rather narrow range between 1.63 and 2.56 mg/kg per day (average, 2.09 mg/kg per day). There was no correlation between extra renal clearance and generation rates. With this simple method, extra renal clearance and generation rates of beta2-m can be determined using data by switching hemodialysis patients from impermeable to permeable membranes.

Age Factors↗
PubMed2005

Kinetic modeling of lipase catalyzed hydrolysis of (R/S)-1-methoxy-2-propyl-acetate as a model reaction for production of chiral secondary alcohols.

The Candida antarctica lipase B catalyzed kinetic resolution of (R/S)-1-methoxy-2-propyl-acetate was studied as a model system for the biocatalytic production of chiral secondary alcohols. For this purpose, a kinetic model is proposed involving both enantiomers of this reaction using model discrimination and parameter identification. Starting from a ping-pong bi-bi mechanism, a simplified model with sensitive parameters was derived for the R- and S-enantiomer, respectively. It was validated at pH 7.0, using time-course measurements at varying temperatures (30-60 degrees C) and initial substrate conditions (0.05-1.5 M). This model was then used for mechanistic interpretation of the kinetic resolution on a biochemical level. The effect of temperature on kinetic parameters and enantiomeric ratio was investigated and compared to findings from the field of molecular modeling to obtain a better understanding of the reaction system for process design. Values of 21.2 and 9.7 kJmol-1 were determined for the enthalpic (DeltaR-S DeltaH ++ degrees) and the entropic (-T x DeltaR-S DeltaS ++ degrees) contribution of the difference in transition state energy of both enantiomers at 30 degrees C. High enantiomeric ratio's (E of 47-110) especially at lower temperatures, in addition to enzyme activity at a wide pH range, indicate this biotransformation is a promising example for the industrial production of chiral secondary alcohols.

Fungal Proteins↗
PubMed1993

Validation of nitrogen-13-ammonia tracer kinetic model for quantification of myocardial blood flow using PET.

Positron emission tomography has been shown to provide quantitative estimates of myocardial blood flow using 13N-ammonia and 15O-water. In a validation study, myocardial blood flow was noninvasively determined in 11 open-chest anesthetized dogs using dynamic positron emission tomography. The radiopharmaceuticals 13N-ammonia and 15O-water were intravenously administered and measurements were carried out at rest and following pharmacological vasodilation to assess blood flow over a range from 53 to 580 ml/100 g/min. Quantification of blood flow based on tracer kinetic modeling of 13N-ammonia data correlated closely with myocardial blood flow determined by microspheres (y = 0.944 x +7.22, r = 0.986) and with the 15O-water injection technique y = 1.054 x -15.8 (r = 0.99). The use of 13N-ammonia with positron emission tomography enables the accurate quantification of myocardial blood flow. Using this technique, uncomplicated study protocols simplify the measurement procedures while providing excellent qualitative and quantitative information.

Ammonia↗
PubMed1988

General kinetic model for protein-mediated phospholipid transfer between membranes.

Phospholipid transfer protein catalyzes the transfer of phospholipids between bilayer membranes. A general model is developed for describing the kinetics of this process. While previous models derive detailed expressions only for the initial rate of transfer from donor to acceptor membranes, this model takes into account donor-to-donor, acceptor-to-acceptor, and acceptor-to-donor transfers, in addition to the usual donor-to-acceptor transfer. The apparent rate of transfer along any of these specific routes is given as the product of the total rate of transfer (the sum of the rates of transfer along all four routes) and a probability function uniquely defined for each route. The model explains adequately the effects of membrane concentration on phospholipid transfer activity as well as the consequences of varying membrane surface charge and size. Using bovine liver phosphatidylcholine transfer protein, the model is applied to the kinetic analysis of phosphatidylcholine transfer between two populations of small unilamellar vesicles. Rates of protein-catalyzed phosphatidylcholine transfer between vesicles with identical phosphatidic acid content (2 or 6 mol%) are determined experimentally as a function of total vesicle concentration to calculate apparent dissociation constants and maximum rates of transfer; apparent rates of transfer between various combinations of vesicles containing 2 or 6 mol% phosphatidic acid are then deduced from the derived velocity expression. Reasonably good agreement is seen between theoretical apparent rate-vesicle concentration relationships and those measured experimentally. The results support the general treatment of the kinetics of protein-mediated phospholipid transfer and permit an estimation of useful kinetic parameters.

Animals↗
PubMed1996

Kinetic model for phototransduction and G-protein enzyme cascade: understanding quantal bumps during inhibition of CaM-KII or PP2B.

We utilize a computer model derived directly from the phototransductive enzyme cascade involving rhodopsin (R), G-proteins (G) and ultimately the membrane channels. In photoreceptors, single photons activate single rhodopsin molecules (R*), resulting in the production of quantal bumps. A CaM-KII inhibitor may inhibit whereas calcineurin (PP2B) inhibitors may augment arrestin activity. Arrestin is known to inactivate R*. We voltage-clamped and digitized quantal bumps for comparison with the kinetic model and simulations. Inhibitors of CaM-KII and PP2B produce results consistent with altering arrestin activity. In sum, we have succeeded in constructing a mathematical description of the phototransduction cascade that is biochemically derived and useful in interpreting results.

Animals↗
PubMed1988

Anion activation of dopamine beta-hydroxylase: a kinetic model.

1. A theoretical analysis has been made of the mechanism of anion activation of dopamine beta-hydroxylase on the basis of accumulated experimental data. A model is presented that accounts for the numerous different effects of activating anions on the enzyme kinetics. This model has a general validity, since it holds for any of the kinetic mechanisms thus far proposed for dopamine beta-hydroxylase. 2. It has been shown that the results of this analysis have direct implications for the experimental conditions to be used in the study of the dopamine beta-hydroxylase reaction. 3. The present analysis has proved that, under appropriate assumptions, theoretical treatment of nonessential activation, so far limited to the single-substrate case, can be easily extended to steady-state multireactant enzymes.

Algorithms↗
PubMed1990

A precise and rapid microtitre plate clot lysis assay: methodology, kinetic modeling and measurement of catalytic constants for plasminogen activation during fibrinolysis.

A rapid and precise turbidimetric clot lysis assay employing a microtitre plate reader and personal computer is described in detail. The use of such widely available instrumentation, the convenience and rapid throughput suggest the assay could be developed as a reference method with which to measure the potency of tissue plasminogen activator (t-PA) in conjunction with the WHO reference preparation. The method has been used to investigate molecular parameters involved in fibrinolysis. Aggregation status of the fibrin does not appear to influence the mechanism of plasminogen activation and clot lysis by plasmin. High ratios of plasminogen to fibrin resulted in a change in clot turbidity and in a change in the lysis profile of turbidity versus time. This is probably the result of plasminogen binding to fibrin and consequent restriction of the access of plasmin to its sites of cleavage in the fibrin. A simple model is proposed, and equations have been derived, for the kinetics of lysis which adequately describe the mechanism and which are confirmed by experimental data. This model results in estimates of the Km and kcat for the activation of plasminogen by t-PA during clot lysis of approximately 150 nM and 0.1 s-1, respectively, in excellent agreement with published values. The assay should therefore prove useful in quantitative evaluations of the molecular phenomena occurring during fibrinolysis. The more rapid activation of lys-plasminogen than glu-plasminogen by t-PA was confirmed. However, evidence was obtained that the lys-form binds more tightly to fibrin by the same factor. This observation suggested that the appropriate substrate in the kinetic model is fibrin-bound plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Buffers↗