The regulatory design of an allosteric feedback loop: the effect of saturation by pathway substrate

2002 ◽  
Vol 30 (2) ◽  
pp. 19-25 ◽  
Author(s):  
S. Hofmeyr Jan-Hendrik ◽  
Brett G. Olivier
Keyword(s):  
Steady State ◽  
Metabolic Regulation ◽  
Supply And Demand ◽  
Graphical Analysis ◽  
Degree Of Saturation ◽  
Rate Equations ◽  
Distinct Advantage ◽  
Control Analysis ◽  
Hill Model ◽  
Wide Range

Aspects of metabolic regulation can be fruitfully studied with a combination of generic modelling, control analysis and graphical analysis using rate characteristics. This paper analyses a prototypical supply-demand system consisting of a biosynthetic subsystem subject to allosteric inhibition by its product and a demand process that consumes this product. The effect of changes in affinity of the committing supply enzyme for the pathway substrate on the regulatory properties of the supply subsystem is compared for the Monod-Wyman-Changeux and the reversible Hill allosteric enzyme models. We found that the Hill model has a distinct advantage in that the steady-state concentration at which it maintains the product is set by the half-saturating product concentration and is independent of changes in the degree of saturation for substrate. In contrast, with the Monod-Wyman-Changeux model this set point varies with affinity for substrate. Explicitly incorporating reversibility in all rate equations made it possible to distinguish between kinetic and thermodynamic aspects of regulation. Combining the supply and demand rate characteristics allows us to explore both the control distribution at steady state and the regulatory performance of the system over a wide range of demand activities.

scholarly journals Quantitative determination of the steady-state kinetics of multienzyme reactions using the algebraic rate equations for the component single-enzyme reactions

1993 ◽  
Vol 291 (2) ◽  
pp. 585-593 ◽  
Author(s):  
C D Stoner
Keyword(s):  
Steady State ◽  
Direct Calculation ◽  
Rate Equations ◽  
Maximum Efficiency ◽  
Control Analysis ◽  
Flux Control ◽  
Enzyme Reactions ◽  
Dependent Variables ◽  
The Individual ◽  
Single Enzyme

Methods are given whereby the steady-state kinetic characteristics of multienzyme reactions consisting of individual single-enzyme reactions linked by freely diffusible intermediates can be determined quantitatively from the experimentally determined complete algebraic rate equations for the individual reactions. The approach is based on the fact that a valid steady-state rate equation for such a multienzyme reaction, in terms of the rate equations for the individual reactions, can be obtained simply from knowledge of the relative rates of the individual reactions when the multienzyme reaction is in the steady state. A number of model multienzyme reactions, which differ as to structural arrangement of the individual reactions, are examined by this approach. Simple mathematical methods which are applicable to most of these models are given for direct calculation of dependent variables. It is either pointed out or demonstrated with Mathematica that the rate equations for all of these models can be handled very easily with the aid of a personal computer equipped with appropriate equation-solving software. Since the approach permits evaluation of all dependent variables for any specific combination of values for the kinetic parameters and independent variables, numerical values for the flux control coefficients of the individual enzymes can be obtained by direct calculation for a wide variety of conditions and can be compared with those obtained according to the methods of Metabolic Control Analysis. Several such comparisons have been made and in all cases identical results were obtained. The intuitive notion that the individual enzymes of a multienzyme reaction would be equally rate limiting if the total amount of enzyme were being used with maximum efficiency is tested and shown to be incorrect. In the course of this test the flux control coefficient for the individual enzymes were found to be appropriate indicators of relative rate limitation or control by the enzymes and to account properly for differences in specific activity among the enzymes.

Spectroscopic Studies of Asparaginyl-tRNA Synthetase from Entamoeba histolytica

2019 ◽  
Vol 26 (6) ◽  
pp. 435-448
Author(s):  
Priyanka Biswas ◽  
Dillip K. Sahu ◽  
Kalyanasis Sahu ◽  
Rajat Banerjee
Keyword(s):  
Circular Dichroism ◽  
Steady State ◽  
Entamoeba Histolytica ◽  
Protein Concentration ◽  
Trna Synthetase ◽  
Solvent Exposure ◽  
Steady State Fluorescence ◽  
State Process ◽  
Wide Range ◽  
Circular Dichroïsm

Background: Aminoacyl-tRNA synthetases play an important role in catalyzing the first step in protein synthesis by attaching the appropriate amino acid to its cognate tRNA which then transported to the growing polypeptide chain. Asparaginyl-tRNA Synthetase (AsnRS) from Brugia malayi, Leishmania major, Thermus thermophilus, Trypanosoma brucei have been shown to play an important role in survival and pathogenesis. Entamoeba histolytica (Ehis) is an anaerobic eukaryotic pathogen that infects the large intestines of humans. It is a major cause of dysentery and has the potential to cause life-threatening abscesses in the liver and other organs making it the second leading cause of parasitic death after malaria. Ehis-AsnRS has not been studied in detail, except the crystal structure determined at 3 Å resolution showing that it is primarily α-helical and dimeric. It is a homodimer, with each 52 kDa monomer consisting of 451 amino acids. It has a relatively short N-terminal as compared to its human and yeast counterparts. Objective: Our study focusses to understand certain structural characteristics of Ehis-AsnRS using biophysical tools to decipher the thermodynamics of unfolding and its binding properties. Methods: Ehis-AsnRS was cloned and expressed in E. coli BL21DE3 cells. Protein purification was performed using Ni-NTA affinity chromatography, following which the protein was used for biophysical studies. Various techniques such as steady-state fluorescence, quenching, circular dichroism, differential scanning fluorimetry, isothermal calorimetry and fluorescence lifetime studies were employed for the conformational characterization of Ehis-AsnRS. Protein concentration for far-UV and near-UV circular dichroism experiments was 8 µM and 20 µM respectively, while 4 µM protein was used for the rest of the experiments. Results: The present study revealed that Ehis-AsnRS undergoes unfolding when subjected to increasing concentration of GdnHCl and the process is reversible. With increasing temperature, it retains its structural compactness up to 45ºC before it unfolds. Steady-state fluorescence, circular dichroism and hydrophobic dye binding experiments cumulatively suggest that Ehis-AsnRS undergoes a two-state transition during unfolding. Shifting of the transition mid-point with increasing protein concentration further illustrate that dissociation and unfolding processes are coupled indicating the absence of any detectable folded monomer. Conclusion: This article indicates that GdnHCl induced denaturation of Ehis-AsnRS is a two – state process and does not involve any intermediate; unfolding occurs directly from native dimer to unfolded monomer. The solvent exposure of the tryptophan residues is biphasic, indicating selective quenching. Ehis-AsnRS also exhibits a structural as well as functional stability over a wide range of pH.

scholarly journals Portable near Infrared Spectroscopy as a Tool for Fresh Tomato Quality Control Analysis in the Field

2021 ◽  
Vol 11 (7) ◽  
pp. 3209
Author(s):  
Karla R. Borba ◽  
Didem P. Aykas ◽  
Maria I. Milani ◽  
Luiz A. Colnago ◽  
Marcos D. Ferreira ◽  
...  
Keyword(s):  
Citric Acid ◽  
Near Infrared ◽  
Prediction Models ◽  
Quality Attributes ◽  
Internal Quality ◽  
Control Analysis ◽  
Tomato Quality ◽  
Wide Range ◽  
Different Types ◽  
Fresh Tomato

Portable spectrometers are promising tools that can be an alternative way, for various purposes, of analyzing food quality, such as monitoring in a few seconds the internal quality during fruit ripening in the field. A portable/handheld (palm-sized) near-infrared (NIR) spectrometer (Neospectra, Si-ware) with spectral range of 1295–2611 nm, equipped with a micro-electro-mechanical system (MEMs), was used to develop prediction models to evaluate tomato quality attributes non-destructively. Soluble solid content (SSC), fructose, glucose, titratable acidity (TA), ascorbic, and citric acid contents of different types of fresh tomatoes were analyzed with standard methods, and those values were correlated to spectral data by partial least squares regression (PLSR). Fresh tomato samples were obtained in 2018 and 2019 crops in commercial production, and four fruit types were evaluated: Roma, round, grape, and cherry tomatoes. The large variation in tomato types and having the fruits from distinct years resulted in a wide range in quality parameters enabling robust PLSR models. Results showed accurate prediction and good correlation (Rpred) for SSC = 0.87, glucose = 0.83, fructose = 0.87, ascorbic acid = 0.81, and citric acid = 0.86. Our results support the assertion that a handheld NIR spectrometer has a high potential to simultaneously determine several quality attributes of different types of tomatoes in a practical and fast way.

scholarly journals Identification of DC Thermal Steady-State Differential Inductance of Ferrite Power Inductors

Energies ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3854
Author(s):  
Salvatore Musumeci ◽  
Luigi Solimene ◽  
Carlo Stefano Ragusa
Keyword(s):  
Steady State ◽  
Input Voltage ◽  
Switching Frequency ◽  
Ohmic Losses ◽  
Steady State Temperature ◽  
Wide Range ◽  
Average Current ◽  
Power Inductors ◽  
Saturable Inductor ◽  
Thermal Steady State

In this paper, we propose a method for the identification of the differential inductance of saturable ferrite inductors adopted in DC–DC converters, considering the influence of the operating temperature. The inductor temperature rise is caused mainly by its losses, neglecting the heating contribution by the other components forming the converter layout. When the ohmic losses caused by the average current represent the principal portion of the inductor power losses, the steady-state temperature of the component can be related to the average current value. Under this assumption, usual for saturable inductors in DC–DC converters, the presented experimental setup and characterization method allow identifying a DC thermal steady-state differential inductance profile of a ferrite inductor. The curve is obtained from experimental measurements of the inductor voltage and current waveforms, at different average current values, that lead the component to operate from the linear region of the magnetization curve up to the saturation. The obtained inductance profile can be adopted to simulate the current waveform of a saturable inductor in a DC–DC converter, providing accurate results under a wide range of switching frequency, input voltage, duty cycle, and output current values.

SET-VALUED PERFORMANCE APPROXIMATIONS FOR THE QUEUE GIVEN PARTIAL INFORMATION

2020 ◽  
pp. 1-23
Author(s):  
Yan Chen ◽  
Ward Whitt
Keyword(s):  
Steady State ◽  
Decay Rate ◽  
Waiting Time ◽  
Partial Information ◽  
Upper And Lower Bounds ◽  
Interarrival Time ◽  
Limited Information ◽  
Wide Range ◽  
The Mean ◽  
Third Moment

In order to understand queueing performance given only partial information about the model, we propose determining intervals of likely values of performance measures given that limited information. We illustrate this approach for the mean steady-state waiting time in the $GI/GI/K$ queue. We start by specifying the first two moments of the interarrival-time and service-time distributions, and then consider additional information about these underlying distributions, in particular, a third moment and a Laplace transform value. As a theoretical basis, we apply extremal models yielding tight upper and lower bounds on the asymptotic decay rate of the steady-state waiting-time tail probability. We illustrate by constructing the theoretically justified intervals of values for the decay rate and the associated heuristically determined interval of values for the mean waiting times. Without extra information, the extremal models involve two-point distributions, which yield a wide range for the mean. Adding constraints on the third moment and a transform value produces three-point extremal distributions, which significantly reduce the range, producing practical levels of accuracy.

scholarly journals Modelling the atmosphere of lava planet K2-141b: implications for low- and high-resolution spectroscopy

2020 ◽  
Vol 499 (4) ◽  
pp. 4605-4612
Author(s):  
T Giang Nguyen ◽  
Nicolas B Cowan ◽  
Agnibha Banerjee ◽  
John E Moores
Keyword(s):  
Steady State ◽  
Ocean Circulation ◽  
Scale Height ◽  
High Resolution Spectroscopy ◽  
Return Flow ◽  
High Dispersion ◽  
Magma Ocean ◽  
Steady State Flow ◽  
Wide Range ◽  
Very High

ABSTRACT Transit searches have uncovered Earth-size planets orbiting so close to their host star that their surface should be molten, so-called lava planets. We present idealized simulations of the atmosphere of lava planet K2-141b and calculate the return flow of material via circulation in the magma ocean. We then compare how pure Na, SiO, or SiO2 atmospheres would impact future observations. The more volatile Na atmosphere is thickest followed by SiO and SiO2, as expected. Despite its low vapour pressure, we find that a SiO2 atmosphere is easier to observe via transit spectroscopy due to its greater scale height near the day–night terminator and the planetary radial velocity and acceleration are very high, facilitating high dispersion spectroscopy. The special geometry that arises from very small orbits allows for a wide range of limb observations for K2-141b. After determining the magma ocean depth, we infer that the ocean circulation required for SiO steady-state flow is only 10−4 m s−1, while the equivalent return flow for Na is several orders of magnitude greater. This suggests that a steady-state Na atmosphere cannot be sustained and that the surface will evolve over time.

scholarly journals Rate Equation Modelling of Nonlinear Dynamics in Directly Modulated Multiple Quantum Well Laser Diodes

VLSI Design ◽  
1998 ◽  
Vol 8 (1-4) ◽  
pp. 355-360 ◽  
Author(s):  
Stephen Bennett ◽  
Christopher M. Snowden ◽  
Stavros Iezekiel
Keyword(s):  
Nonlinear Dynamics ◽  
Quantum Well ◽  
Multiple Quantum Well ◽  
Period Doubling ◽  
Rate Equations ◽  
Multiple Quantum ◽  
Quantum Well Laser ◽  
Wide Range ◽  
Multiple Quantum Well Laser ◽  
Good Agreement

A theoretical (using rate equations) and experimental study of the nonlinear dynamics of a distributed feedback multiple quantum well laser diode is presented. The analysis is performed under direct modulation. Period doubling and period tripling are identified in both the measurements and simulations. Period doubling is found over a wide range of modulation frequencies in the laser. Computational results using rate equations show good agreement with the experimental results.

scholarly journals Foslevodopa/Foscarbidopa Is Well Tolerated and Maintains Stable Levodopa and Carbidopa Exposure Following Subcutaneous Infusion

2021 ◽  
pp. 1-8
Author(s):  
Matthew Rosebraugh ◽  
Wei Liu ◽  
Melina Neenan ◽  
Maurizio F. Facheris
Keyword(s):  
Steady State ◽  
Phase 1 ◽  
The United States ◽  
Therapeutic Window ◽  
Fixed Dose ◽  
Advanced Parkinson’S Disease ◽  
Subcutaneous Infusion ◽  
Study Results ◽  
Wide Range ◽  
Favorable Safety

Background: Foslevodopa/foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson’s disease (aPD). Objective: The current work characterizes the levodopa (LD) and carbidopa (CD) pharmacokinetics (PK) following SC infusions of foslevodopa/foscarbidopa delivered at four different infusion rates in PD patients. Methods: This was a Phase 1, single ascending dose, single-blind study conducted in 28 adult male and female subjects at seven sites in the United States. Foslevodopa/foscarbidopa was administered via abdominal SC infusion in PD patients over 72 hours. Patients were stratified in 4 groups and received a fixed dose of foslevodopa/foscarbidopa based on their oral daily LD intake. Serial plasma PK samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. Results: LD exposure quickly reached steady state and remained stable with minimal fluctuations. Foslevodopa/foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups. Conclusion: Foslevodopa/foscarbidopa was able to provide stable LD and CD exposures in PD patients over 72 hours via SC route of delivery with very low fluctuation in LD concentration level across a wide range of clinically relevant exposures. Foslevodopa/foscarbidopa had a favorable safety profile. The low PK fluctuation following foslevodopa/foscarbidopa infusion is expected to maintain LD exposure to treat aPD patients within a narrow therapeutic window.

Peroxidase: a multifunctional enzyme in grapevines

2003 ◽  
Vol 30 (6) ◽  
pp. 577 ◽  
Author(s):  
Alfonso Ros Barceló ◽  
Federico Pomar ◽  
Matías López-Serrano ◽  
Maria Angeles Pedreño
Keyword(s):  
Cell Wall ◽  
Metabolic Regulation ◽  
Trichoderma Viride ◽  
Visible Spectrum ◽  
H2o2 Production ◽  
Class Iii ◽  
Absorption Bands ◽  
Peroxidase Isoenzyme ◽  
Wide Range ◽  
Uv C

Peroxidases are heme-containing enzymes that catalyse the one-electron oxidation of several substrates at the expense of H2O2. They are probably encoded by a large multigene family in grapevines, and therefore show a high degree of polymorphism. Grapevine peroxidases are glycoproteins of high thermal stability, whose molecular weight usually ranges from 35 to 45 kDa. Their visible spectrum shows absorption bands characteristic of high-spin class III peroxidases. Grapevine peroxidases are capable of accepting a wide range of natural compounds as substrates, such as the cell wall protein extensin, plant growth regulators such as IAA, and phenolics such as benzoic acids, stilbenes, flavonols, cinnamyl alcohols and anthocyanins. They are located in cell walls and vacuoles. These locations are in accordance with their key role in determining the final cell wall architecture, especially regarding lignin deposition and extensin insolubilization, and the turnover of vacuolar phenolic metabolites, a task that also forms part of the molecular program of disease resistance. Although peroxidase is a constitutive enzyme in grapevines, its levels are strongly modulated during plant cell development and in response to both biotic and abiotic environmental factors. To gain an insight into the metabolic regulation of peroxidase, several authors have studied how grapevine peroxidase and H2O2 levels change in response to a changing environment. Nevertheless, the results obtained are not always easy to interpret. Despite such difficulties, the response of the peroxidase–H2O2 system to both UV-C radiation and Trichoderma viride elicitors is worthy of study. Both UV-C and T. viride elicitors induce specific changes in peroxidase isoenzyme / H2O2 levels, which result in specific changes in grapevine physiology and metabolism. In the case of T. viride-elicited grapevine cells, they show a particular mechanism for H2O2 production, in which NADPH oxidase-like activities are apparently not involved. However, they offer a unique system whereby the metabolic regulation of peroxidase by H2O2, with all its cross-talks and downstream signals, may be elegantly dissected.

Study of Temperature Effect on Servovalve-Controlled Fuel Metering Unit

2015 ◽  
Vol 137 (6) ◽  
Author(s):  
Bin Wang ◽  
Haocen Zhao ◽  
Ling Yu ◽  
Zhifeng Ye
Keyword(s):  
Steady State ◽  
Temperature Variation ◽  
Dynamic Characteristics ◽  
Numerical Study ◽  
Step Response ◽  
Fuel Temperature ◽  
Wide Range ◽  
Fuel Rate ◽  
Testing Condition ◽  
The Given

It is usual that fuel system of an aero-engine operates within a wide range of temperatures. As a result, this can have effect on both the characteristics and precision of fuel metering unit (FMU), even on the performance and safety of the whole engine. This paper provides theoretical analysis of the effect that fluctuation of fuel temperature has on the controllability of FMU and clarifies the drawbacks of the pure mathematical models considering fuel temperature variation for FMU. Taking the electrohydraulic servovalve-controlled FMU as the numerical study, simulation in AMESim is carried out by thermal hydraulic model under the temperatures ranged from −10 to 60 °C to confirm the effectiveness and precision of the model on the basis of steady-state and dynamic characteristics of FMU. Meanwhile, the FMU testing workbench with temperature adjustment device employing the fuel cooler and heater is established to conduct an experiment of the fuel temperature characteristics. Results show that the experiment matches well with the simulation with a relative error no more than 5% and that 0–50 °C fuel temperature variation produces up to 5.2% decrease in fuel rate. In addition, step response increases with the fuel temperature. Fuel temperature has no virtual impact on the steady-state and dynamic characteristics of FMU under the testing condition in this paper, implying that FMU can operate normally in the given temperature range.

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