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At least 415 records · Page 23Linked to original sources
PubMed1982

Kinetic model for surface-active enzymes based on the Langmuir adsorption isotherm: phospholipase C (Bacillus cereus) activity toward dimyristoyl phosphatidylcholine/detergent micelles.

A simple kinetic model for the enzymatic activity of surface-active proteins against mixed micelles has been developed. This model uses the Langmuir adsorption isotherm, the classic equation for the binding of gas molecules to metal surfaces, to characterize enzyme adsorption to micelles. The number of available enzyme binding sites is equated with the number of substrate and inhibitor molecules attached to micelles; enzyme molecules are attracted to the micelle due to the affinity of the enzyme active site for the molecules in the micelle. Phospholipase C (Bacillus cereus) kinetics in a wide variety of dimyristoyl phosphatidylcholine/detergent micelles are readily explained by this model and the assumption of competitive binding of the detergent at the enzyme active site. Binding of phospholipase C to pure detergent micelles is demonstrated by gel filtration chromatography. The experimentally determined enzyme-detergent micelle binding constants are used directly in the rate equation. The Langmuir adsorption model predicts a variety of the characteristics observed for phospholipase kinetics, such as differential inhibition by various charged, uncharged, and zwitterionic detergents and surface-dilution inhibition. The essential idea of this model, that proteins can be attracted and bound to bilayers or micelles by possessing a binding site for the molecules composing the surface, may have wider application in the study of water-soluble (extrinsic) protein-membrane interactions.

Bacillus cereus↗
PubMed2007

From here to eternity: a unified kinetic model for the pathophysiology of atherosclerotic events.

Two operative pathophysiological models underlie the clinical management of ischemic heart disease: a physical model founded on the magnitude of vascular stenosis and a biochemical model founded on the inflammatory processes within the atherosclerotic plaque. Despite their complementary natures, these 2 models are implicitly competitive--the stenotic model supporting the primacy of aggressive interventional procedures and the inflammatory model supporting the primacy of conservative medical management. We unified these alternative perspectives through a kinetic model that characterizes the pathophysiology of cardiovascular events as a network of exponential transitions between the inflammatory and stenotic states. According to this model, the prevalence of the normative (nonstenotic and noninflammatory) state falls exponentially, while the prevalences of the inflammatory and stenotic states rise to a peak and then fall off exponentially. According to this model, event rate increases as a complex function of both myocardial ischemia and vascular inflammation. Although the model has yet to be prospectively validated, it provides a theoretical foundation for predicting the degree to which atherosclerotic events are due to inflammation versus stenosis and the degree to which they can thereby be prevented by treatment strategies directed at plaque stabilization or relief of ischemia.

Coronary Artery Disease↗
PubMed2006

The kinetic model of the shikimate pathway as a tool to optimize enzyme assays for high-throughput screening.

Four-enzyme section of the shikimate pathway (Aro B, D, E, and K) of Streptococcus pneumoniae has been studied. Kinetic properties of the individual enzymes and three- and four-enzyme linked reactions have been characterized in vitro. On the basis of the data measured in spectrophotometric and LC-MS experiments, kinetic mechanisms of the enzymes have been suggested and all kinetic parameters have been identified. Kinetic models for these three- and four-enzyme sections of the shikimate pathway have been constructed and validated. The model of the four-enzyme section of shikimate pathway has been employed to design an inhibition-sensitive reconstituted pathway for a high-throughput screening effort on the shikimate pathway. It was demonstrated that using the model it was possible to optimize this reconstituted pathway in such a way to provide equal sensitivity of the enzymes to inhibition.

Alcohol Oxidoreductases↗
PubMed1995

A two-binding-site kinetic model for the ribonuclease-T1-catalysed transesterification of dinucleoside phosphate substrates.

Ribonucleases have been found to have subsites that confer large rate enhancements but do not contribute to substrate binding. In this study, we present a kinetic model that formally explains how subsite binding energy is converted into chemical activation energy. The proposed mechanism takes into account a primary specificity site and a subsite, both of which must be occupied for chemical turnover. An unstable reaction intermediate is formed upon binding of the polymeric substrate monomers at the corresponding subsites. The structure of this reaction intermediate resembles the transition state of the catalysed transphosphorylation reaction. Similar mechanisms may be used by other depolymerizing enzymes including nucleases, glycosidases, and proteases.

Binding Sites↗
PubMed2004

Kinetic models of sorption: a theoretical analysis.

The kinetics of sorption from a solution onto an adsorbent has been explored theoretically. The general analytical solution was obtained for two cases. It has been shown that at high initial concentration of solute (sorbate) the general equation converts to a pseudo-first-order model and at lower initial concentration of solute it converts to a pseudo-second-order model. In other words, the sorption process obeys pseudo-first-order kinetics at high initial concentration of solute, while it obeys pseudo-second-order kinetics model at lower initial concentration of solute. The theoretical results (derived equations) show that the observed rate constants of pseudo-first-order and pseudo-second-order models are combinations of adsorption and desorption rate constants and also initial concentration of solute. The obtained theoretical equations are used to correlate experimental data for sorption kinetics of some solutes on various sorbents. The predictions of the theory are in excellent agreement with the experimental data.

Journal Article↗
PubMed2006

Thermodynamic and kinetic modeling of transcriptional pausing.

We present a statistical mechanics approach for the prediction of backtracked pauses in bacterial transcription elongation derived from structural models of the transcription elongation complex (EC). Our algorithm is based on the thermodynamic stability of the EC along the DNA template calculated from the sequence-dependent free energy of DNA-DNA, DNA-RNA, and RNA-RNA base pairing associated with (i) the translocational and size fluctuations of the transcription bubble; (ii) changes in the associated DNA-RNA hybrid; and (iii) changes in the cotranscriptional RNA secondary structure upstream of the RNA exit channel. The calculations involve no adjustable parameters except for a cutoff used to discriminate paused from nonpaused complexes. When applied to 100 experimental pauses in transcription elongation by Escherichia coli RNA polymerase on 10 DNA templates, the approach produces statistically significant results. We also present a kinetic model for the rate of recovery of backtracked paused complexes. A crucial ingredient of our model is the incorporation of kinetic barriers to backtracking resulting from steric clashes of EC with the cotranscriptionally generated RNA secondary structure, an aspect not included explicitly in previous attempts at modeling the transcription elongation process.

Computational Biology↗
PubMed1998

A kinetic model on calcium residues and facilitation.

The role of calcium as a regulator for neuronal function is very important. Calcium initiates many reactions that determine the behavior of the neuronal cell. In this article we use a kinetic model of the presynaptic synapsin I protein. This protein is responsible, via phosphorylation, for regulating the amount of transmitter vesicles available for release. This protein has been shown to inhibit the amount of vesicles ready for release in its dephosphorylated state, and releases its inhibitory binding due to phosphorylation. The phosphorylation of synapsin I depends on cyclic adenosine monophosphate and type II calcium/calmodulin protein kinase. Due to the duration of these two second messengers, we show that short-term facilitation does not have to depend on calcium residues. Furthermore, we show that calcium residues (in parts of microM range) promote increased facilitation due to the additional calcium reacting with the second messenger system.

Action Potentials↗
PubMed1991

Precision of hemodialysis urea kinetic modeling: empirical data and Monte Carlo simulation.

To examine the precision of variable volume urea kinetic modeling (UKMv) 15 stable hemodialysis patients were followed with repeated sampling for 5 weeks. Samples were frozen and later submitted to careful batch analysis. On average, the index for dialysis adequacy (Kt/V) varied 6.1% and normalized protein catabolic rate (pcr) varied 10.5%. Immediate routine analysis correspondingly rendered 8.6% and 13.2%. A simpler, fixed volume model (UKMf) had an almost similar variation and results correlated highly with UKMv. The duration of the preceding interval does not affect Kt/V, but per is lower during longer intervals. Computer simulation demonstrated that most of the variation of calculated pcr could be explained by fluctuations of urea generation, i.e., secondary to dietary changes. Fluctuations in the efficiency of dialysis may cause most variation of Kt/V, but the imprecision of the urea analysis also contributes. Precise knowledge of effective dialyzer clearance is not important for the calculation of Kt/V and pcr. It is concluded that calculating these variables with a simple model, employing a reasonable estimate of dialyzer clearance will suffice for routine use. The slightly higher accuracy of a more sophisticated model is overshadowed by day-to-day variations.

Adult↗
PubMed1993

Kinetic models of coupling between H+ and Na(+)-translocation and ATP synthesis/hydrolysis by F0F1-ATPases: can a cell utilize both delta mu H+ and delta mu Na+ for ATP synthesis under in vivo conditions using the same enzyme?

Kinetic models of the F0F1-ATPase able to transport H+ or/and Na+ ions are proposed. It is assumed that (i) H+ and Na+ compete for the same binding sites, (ii) ion translocation through F0 is coupled to the rate-limiting step of the F1-catalyzed reaction. The main characteristics of the dependences of ATP synthesis and hydrolysis rates on delta psi, delta pH, and delta pNa are predicted for various versions of the coupling model. The mechanism of the switchover from delta mu H(+)-dependent synthesis to the delta mu Na(+)-dependent one is demonstrated. It is shown that even with a drastic drop in delta mu H+, ATP hydrolysis by the proton mode of catalysis can be effectively inhibited by delta psi and delta pNa. The results obtained strongly support the possibility that the same F0F1-ATPase in bacterial cells can utilize both delta muH+ and delta muNa+ for ATP synthesis under in vivo conditions.

Adenosine Triphosphate↗
PubMedDate not supplied

[Kinetic model of a multienzyme system of blood prostanoid synthesis. II. Dynamic responses to pharmacological agents--inhibitors of prostaglandin H synthetases].

The dynamic replies of the multienzyme system of blood prostanoid synthesis to the introduction of an irreversible inhibitor of prostaglandin H synthetase (PGH synthetase) have been analysed by using kinetic modelling. The alterations of arachidonic acid and PGH synthetase concentrations in platelets and endothelium and the concentrations of thromboxane and prostacyclin have been demonstrated. Particularities of kinetic behaviour of the system probably providing the therapeutic effect of non-steroidal anti-inflammatory drugs have been shown. Namely, the kinetic wave of free arachidonic acid and prostacyclin concentration with respect to thromboxane concentration appears after introduction of the drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1983

Assessment of the [18F]fluorodeoxyglucose kinetic model in calculations of myocardial glucose metabolism during ischemia.

The lumped constant--a term in the operational equation of the Sokoloff tracer kinetic model for deoxyglucose that accounts for the difference in transport and phosphorylation between glucose and its analog, deoxyglucose--could potentially vary from normal to ischemic conditions in the heart. To test the stability of the lumped constant during ischemia, we evaluated the ratio of the extraction fraction for (F-18)-fluorodeoxyglucose (FDG) to that for glucose (a measure of the lumped constant if there is no significant dephosphorylation of FDG-6-PO4) and the rate constant for dephosphorylation of FDG-6-PO4 (k4*) in the isolated, arterially perfused interventricular septum of the rabbit during moderate and severe demand-induced and reduced-flow ischemias. The lumped constant and k4* in each of the four ischemic experimental conditions were found not to be significantly different from the value obtained from the nonischemic controls.

Animals↗
PubMed1999

Interdependence of histamine and methylhistamine kinetics: modelling and simulation approach.

In the article a model of histamine kinetics is described. A motivation of this project was to investigate the hypothesis that methylhistamine may be a marker of histamine appearance in plasma. A model has been made to support the hypothesis. Since metabolic and transport pathways of histamine and methylhistamine are complex and not very well known, the relationship between histamine and methylhistamine should be elucidated by mathematical modelling. From experimental data and the information in the literature, a nonlinear and time-varying four-compartment model is proposed. Extensive release of histamine from mast cells when methylhistamine is injected, is modelled as histamine to methylhistamine ratio control loop.

Biomarkers↗
PubMed2002

Cross-bridge kinetics modeled from myoplasmic [Ca2+] and LV pressure at 17 degrees C and after 37 degrees C and 17 degrees C ischemia.

We modeled changes in contractile element kinetics derived from the cyclic relationship between myoplasmic [Ca(2+)], measured by indo 1 fluorescence, and left ventricular pressure (LVP). We estimated model rate constants of the Ca(2+) affinity for troponin C (TnC) on actin (A) filament (TnCA) and actin and myosin (M) cross-bridge (A x M) cycling in intact guinea pig hearts during baseline 37 degrees C perfusion and evaluated changes at 1) 20 min 17 degrees C pressure, 2) 30-min reperfusion (RP) after 30-min 37 degrees C global ischemia during 37 degrees C RP, and 3) 30-min RP after 240-min 17 degrees C global ischemia during 37 degrees C RP. At 17 degrees C perfusion versus 37 degrees C perfusion, the model predicted: A x M binding was less sensitive; A x M dissociation was slower; Ca(2+) was less likely to bind to TnCA with A x M present; and Ca(2+) and TnCA binding was less sensitive in the absence of A x M. Model results were consistent with a cold-induced fall in heart rate from 260 beats/min (37 degrees C) to 33 beats/min (17 degrees C), increased diastolic LVP, and increased phasic Ca(2+). On RP after 37 degrees C ischemia vs. 37 degrees C perfusion, the model predicted the following: A x M binding was less sensitive; A x M dissociation was slower; and Ca(2+) was less likely to bind to TnCA in the absence of A. M. Model results were consistent with reduced myofilament responsiveness to [Ca(2+)] and diastolic contracture on 37 degrees C RP. In contrast, after cold ischemia versus 37 degrees C perfusion, A x M association and dissociation rates, and Ca(2+) and TnCA association rates, returned to preischemic values, whereas the dissociation rate of Ca(2+) from A x M was ninefold faster. This cardiac muscle kinetic model predicted a better-restored relationship between Ca(2+) and cross-bridge function on RP after an eightfold longer period of 17 degrees C than 37 degrees C ischemia.

Actins↗
PubMed2003

Kinetic modeling of a mixed culture of Pseudomonas denitrificans and Bacillus subtilis under aerobic and anoxic operating conditions.

The kinetics of biological denitrification have been studied and several models, with varying degree of complexity, to be used for design purposes have been presented in the recent years. However, most of these kinetic studies were performed with mixed (and not well defined) microbial systems, such as activated sludge. In the present work, kinetic experiments were carried out in order to study the dynamic characteristics of a defined mixed culture of the denitrifiers Pseudomonas denitrificans and Bacillus subtilis under anoxic and aerobic conditions in a defined synthetic medium involving a mixture of organic substrates, in the presence of nitrates and/or nitrites. Denitrification was assumed to occur by the consecutive reduction of nitrates to nitrites and then to nitrogen gas without accumulation of intermediate gaseous products. The behavior of these defined mixed cultures was predicted using a kinetic model based on the kinetic models that have already been developed for each bacterium separately and the predictions were compared with the results from mixed culture experiments. The overall mathematical model that was developed and validated in the present work is capable of describing the behavior of the mixed culture in the above conditions, i.e. the nitrates and nitrites reduction kinetics, the cell growth, and the organic carbon utilization rates.

Bacillus subtilis↗
PubMed1996

Physiologically based kinetic model of effector cell biodistribution in mammals: implications for adoptive immunotherapy.

The goal of the present investigation was to develop a physiologically based kinetic model to describe the biodistribution of immunologically active effector cells in normal and neoplastic tissues of mammals based on the current understanding of lymphocyte trafficking pathways and signals. The model was used to extrapolate biodistribution among different animal species and to identify differences among different effector populations and between intra-arterial and systemic injections. Most importantly, the model was used to discern critical parameters for improving the delivery of effector cells. In the model, the mammalian body was divided into 12 organ compartments, interconnected in anatomic fashion. Each compartment was characterized by blood flow rate, organ volume and lymphatic flow rate, and other physiological and immunological parameters. The resulting set of 45 differential equations was solved numerically. The model was used to simulate the following biodistribution data: (a) nonactivated T lymphocytes in rats; (b) interleukin 2-activated tumor-infiltrating lymphocytes in humans; (c) nonactivated natural killer (NK) cells in rats; and (d) interleukin 2-activated adherent NK cells in mice. Comparisons between simulations and data demonstrated the feasibility of the model and the scaling scheme. The similarities as well as differences in biodistribution of different lymphocyte populations were revealed as results of their trafficking properties. The importance of lymphocyte infiltration from surrounding normal tissues into tumor tissue was found to depend on lymphocyte migration rate, tumor size, and host organ. The study confirmed that treatment with effector cells has not been as impressive as originally promised, due, in part, to the biodistribution problems. The model simulations demonstrated that low effector concentrations in the systemic circulation greatly limited their delivery to tumor. This was due to high retention in normal tissues, especially in the lung. Reducing normal tissue retention through decreasing attachment rate or adhesion site density in the lung by 50% could increase the tumor uptake by approximately 40% for tumor-infiltrating lymphocytes and by approximately 60% for adherent NK cells. Our analysis suggested the following strategies to improve effector cell delivery to tumor: (a) bypassing the initial lung entrapment with administration to the arterial supply of tumor; (b) reducing normal tissue retention using effector cells with high deformability or blocking lymphocyte adhesion to normal vessels; and (c) enhancing tumor-specific capture and arrest by modifying the tumor microenvironment.

Animals↗
PubMed2004

Role of peptide sequence and neighboring residue glycosylation on the substrate specificity of the uridine 5'-diphosphate-alpha-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl transferases T1 and T2: kinetic modeling of the porcine and canine submaxillary gland mucin tandem repeats.

A large family of uridine 5'-diphosphate (UDP)-alpha-N-acetylgalactosamine (GalNAc):polypeptide N-acetylgalactosaminyl transferases (ppGalNAc Ts) initiates mucin-type O-glycan biosynthesis at serine and threonine. The peptide substrate specificities of individual family members are not well characterized or understood, leaving an inability to rationally predict or comprehend sites of O-glycosylation. Recently, a kinetic modeling approach demonstrated neighboring residue glycosylation as a major factor modulating the O-glycosylation of the porcine submaxillary gland mucin 81 residue tandem repeat by ppGalNAc T1 and T2 [Gerken et al. (2002) J. Biol. Chem. 277, 49850-49862]. To confirm the general applicability of this model and its parameters, the ppGalNAc T1 and T2 glycosylation kinetics of the 80+ residue tandem repeat from the canine submaxillary gland mucin was obtained and characterized. To reproduce the glycosylation patterns of both mucins (comprising 50+ serine/threonine residues), specific effects of neighboring peptide sequence, in addition to the previously described effects of neighboring residue glycosylation, were required of the model. Differences in specificity of the two transferases were defined by their sensitivities to neighboring proline and nonglycosylated hydroxyamino acid residues, from which a ppGalNAc T2 motif was identified. Importantly, the model can approximate the previously reported ppGalNAc T2 glycosylation kinetics of the IgA1 hinge domain peptide [Iwasaki, et al. (2003) J. Biol. Chem. 278, 5613-5621], further validating both the approach and the ppGalNAc T2 positional weighting parameters. The characterization of ppGalNAc transferase specificity by this approach may prove useful for the search for isoform-specific substrates, the creation of isoform-specific inhibitors, and the prediction of mucin-type O-glycosylation sites.

Amino Acid Sequence↗
PubMed2004

Bounded water kinetic model of beta-galactosidase in reverse micelles.

In the present investigation, beta-galactosidase was solubilized into Aerosol OT (AOT)/isooctane reverse micelles. Kinetic data for the hydrolysis of o-nitrophenyl-beta-D-galactopyranoside (ONPG) at different pH values and molar ratios of water to AOT (Wo) were collected. It was observed that the usual kinetic model used for beta-galactosidase catalysis in aqueous systems failed to represent the experimental data. A bounded water model, however, showed a better correlation between enzymatic activity and Wo. In contrast to the aqueous system, controlling the water concentration in the reverse micelles allows the rate constants for the reaction between water molecules and glycosyl-enzyme complexes to be evaluated.

Catalysis↗
PubMed2005

Cluster aggregation and fragmentation kinetics model for gelation.

Gelation can occur in polymer, hydrogel, and colloid systems that undergo reversible aggregation-fragmentation (crosslinking accompanied by breakage). Gelation, characterized by rapid divergence of weight-average molecular weight and viscosity due to initial network formation, can be reversed if conditions change. In this paper, reversible aggregation and fragmentation in the pre-gelation time period are modeled with distribution kinetics. Moment equations are obtained from the population balance equation, and solved for eight different rate kernels. We identify the cases for which gelation is possible and obtain the critical values for the rate constants that allow gelation. The model provides a good simulation of published experimental data for aggregation and degradation of plasticized wheat gluten during thermo-mechanical treatments. We also evaluate two closure approximations based on Gamma and log-normal distributions, and conclude that log-normal closure predicts all five possible steady states, in agreement with the Vigil-Ziff criterion, and Gamma closure predicts only three. However, Gamma closure approximates the steady state either closely or exactly, whereas log-normal closure only poorly approximates the steady-state distribution.

Journal Article↗