scholarly journals Analysis of Hill slopes predicted by the four-ligand exponential model for a regulatory enzyme

1986 ◽  
Vol 234 (3) ◽  
pp. 717-726 ◽  
Author(s):  
S Ainsworth

The four-ligand exponential model for a regulatory enzyme is described as it is applied to kinetic studies of yeast pyruvate kinase in which the concentrations of four ligands are systematically varied. The Hill slopes predicted by this model are calculated for the two situations in which the fourth ligand is either a substrate or an effector. It is shown that the individual terms that make up the expression for the Hill slope assist the interpretation of the observed behaviour in terms of the constants employed by the model.

1973 ◽  
Vol 131 (2) ◽  
pp. 287-301 ◽  
Author(s):  
M. G. Irving ◽  
J. F. Williams

Two kinetically distinct forms of pyruvate kinase (EC 2.7.1.40) were isolated from rabbit liver by using differential ammonium sulphate fractionation. The L or liver form, which is allosterically activated by fructose 1,6-diphosphate, was partially purified by DEAE-cellulose chromatography to give a maximum specific activity of 20 units/mg. The L form was allosterically activated by K+ and optimum activity was recorded with 30mm-K+, 4mm-MgADP-, with a MgADP-/ADP2- ratio of 50:1, but inhibition occurred with K+ concentrations in excess of 60mm. No inhibition occurred with either ATP or GTP when excess of Mg2+ was added to counteract chelation by these ligands. Alanine (2.5mm) caused 50% inhibition at low concentrations of phosphoenolpyruvate (0.15mm). The homotropic effector, phosphoenolpyruvate, exhibited a complex allosteric pattern (nH+2.5), and negative co-operative interactions were observed in the presence of low concentrations of this substrate. The degree of this co-operative interaction was pH-dependent, with the Hill coefficient increasing from 1.1 to 3.2 as the pH was raised from 6.5 to 8.0. Fructose 1,6-diphosphate interfered with the activation by univalent ions, markedly decreased the apparent Km for phosphoenolpyruvate from 1.2mm to 0.2mm, and transformed the phosphoenolpyruvate saturation curve into a hyperbola. Concentrations of fructose 1,6-diphosphate in excess of 0.5mm inhibited this stimulated reaction. The M or muscle-type form of the enzyme was not activated by fructose 1,6-diphosphate and gave a maximum specific activity of 0.3 unit/mg. A Michaelis–Menten response was obtained when phosphoenolpyruvate was the variable substrate (Km+0.125mm), and this form was inhibited by ATP, as well as alanine, even in the presence of excess of Mg2+.


2021 ◽  
pp. 136943322110339
Author(s):  
Jian Guo ◽  
Changliang Xiao ◽  
Jiantao Li

A hill with a lattice transmission tower presents complex wind field characteristics. The commonly used computational fluid dynamics (CFD) simulations are difficult to analyze the wind resistance and dynamic responses of the transmission tower due to structural complexity. In this study, wind tunnel tests and numerical simulations are conducted to analyze the wind field of the hill and the dynamic responses of the transmission tower built on it. The hill models with different slopes are investigated by wind tunnel tests to measure the wind field characteristics, such as mean speed and turbulence intensity. The study shows that the existence of a transmission tower reduces the wind speed on the leeward slope significantly but has little effect on the windward slope. To study the dynamic behavior of the transmission tower, a hybrid analysis procedure is used by introducing the measured experimental wind information to the finite element tower model established using ANSYS. The effects of hill slope on the maximum displacement response of the tower are studied. The results show that the maximum value of the response is the largest when the hill slope is 25° compared to those when hill slope is 15° and 35°. The results extend the knowledge concerning wind tunnel tests on hills of different terrain and provide a comprehensive understanding of the interactive effects between the hill and existing transmission tower regarding to the wind field characteristics and structural dynamic responses.


1982 ◽  
Vol 14 (9) ◽  
pp. 1175-1193 ◽  
Author(s):  
R Herz

The question of the extent to which the concrete physical environment allows, causes, or even forces certain forms of behaviour to occur has been excluded from social sciences literature for a long time. More recent studies from environmental psychology show that the built environment, filtered by subjective perceptions, very probably influences the experience and actions of individuals. Town planning and transport planning is orientated towards the needs, demands, or simply the observed behaviour of social groups, segments of the population, and target groups of individuals. However, at this level the evidence about whether a spatiospecific determinant should be added to the sociodemographic, sociocultural, or socioeconomic determinants is very inconclusive. This paper investigates the influence of certain types of area on behaviour, and uses about 70000 weekday records at the level of differentiated groups of people. Everyday behaviour of the groups is quantified by their time budgets and daily programmes with broad groupings of out-of-house activities as well as various indicators of transport mobility. This study shows that with given characteristics of the individual and his household a series of behavioural parameters does not vary in space and thus these parameters can be used as input for behaviourally orientated transport demand models and transferred from one planning area to another.


2007 ◽  
Vol 362 (1486) ◽  
pp. 1841-1845 ◽  
Author(s):  
Tristan Rocheleau ◽  
Steen Rasmussen ◽  
Peter E Nielsen ◽  
Martin N Jacobi ◽  
Hans Ziock

Template-directed replication is known to obey a parabolic growth law due to product inhibition (Sievers & Von Kiedrowski 1994 Nature 369 , 221; Lee et al . 1996 Nature 382 , 525; Varga & Szathmáry 1997 Bull. Math. Biol . 59 , 1145). We investigate a template-directed replication with a coupled template catalysed lipid aggregate production as a model of a minimal protocell and show analytically that the autocatalytic template–container feedback ensures balanced exponential replication kinetics; both the genes and the container grow exponentially with the same exponent. The parabolic gene replication does not limit the protocellular growth, and a detailed stoichiometric control of the individual protocell components is not necessary to ensure a balanced gene–container growth as conjectured by various authors (Gánti 2004 Chemoton theory ). Our analysis also suggests that the exponential growth of most modern biological systems emerges from the inherent spatial quality of the container replication process as we show analytically how the internal gene and metabolic kinetics determine the cell population's generation time and not the growth law (Burdett & Kirkwood 1983 J. Theor. Biol . 103 , 11–20; Novak et al . 1998 Biophys. Chem . 72 , 185–200; Tyson et al . 2003 Curr. Opin. Cell Biol . 15 , 221–231). Previous extensive replication reaction kinetic studies have mainly focused on template replication and have not included a coupling to metabolic container dynamics (Stadler et al . 2000 Bull. Math. Biol . 62 , 1061–1086; Stadler & Stadler 2003 Adv. Comp. Syst . 6 , 47). The reported results extend these investigations. Finally, the coordinated exponential gene–container growth law stemming from catalysis is an encouraging circumstance for the many experimental groups currently engaged in assembling self-replicating minimal artificial cells (Szostak 2001 et al . Nature 409 , 387–390; Pohorille & Deamer 2002 Trends Biotech . 20 123–128; Rasmussen et al . 2004 Science 303 , 963–965; Szathmáry 2005 Nature 433 , 469–470; Luisi et al . 2006 Naturwissenschaften 93 , 1–13). 1


1996 ◽  
Vol 318 (3) ◽  
pp. 997-1006 ◽  
Author(s):  
Derek HERBERT ◽  
Lindsey J PRICE ◽  
Claude ALBAN ◽  
Laure DEHAYE ◽  
Dominique JOB ◽  
...  

The steady-state kinetics of two multifunctional isoforms of acetyl-CoA carboxylase (ACCase) from maize leaves (a major isoform, ACCase1 and a minor isoform, ACCase2) have been investigated with respect to reaction mechanism, inhibition by two graminicides of the aryloxyphenoxypropionate class (quizalofop and fluazifop) and some cellular metabolites. Substrate interaction and product inhibition patterns indicated that ADP and Pi products from the first partial reaction were not released before acetyl-CoA bound to the enzymes. Product inhibition patterns did not match exactly those predicted for an ordered Ter Ter or a random Ter Ter mechanism, but were close to those postulated for an ordered mechanism. ACCase2 was about 1/2000 as sensitive as ACCase1 to quizalofop but only about 1/150 as sensitive to fluazifop. Fitting inhibition data to the Hill equation indicated that binding of quizalofop or fluazifop to ACCase1 was non-cooperative, as shown by the Hill constant (napp) values of 0.86 and 1.16 for quizalofop and fluazifop respectively. Apparent inhibition constant values (K´ from the Hill equation) for ACCase1 were 0.054 µM for quizalofop and 21.8 µM for fluazifop. On the other hand, binding of quizalofop or fluazifop to ACCase2 exhibited positive co-operativity, as shown by the napp values of 1.85 and 1.59 for quizalofop and fluazifop respectively. K´ values for ACCase2 were 1.7 mM for quizalofop and 140 mM for fluazifop. Kinetic parameters for the co-operative binding of quizalofop to maize ACCase2 were close to those of another multifunctional ACCase of limited sensitivity to graminicide, ACC220 from pea. Inhibition of ACCase1 by quizalofop was mixed-type with respect to acetyl-CoA or ATP, but the concentration of acetyl-CoA had the greater effect on the level of inhibition. Neither ACCase1 nor ACCase2 was appreciably sensitive to CoA esters of palmitic acid (16:0) or oleic acid (18:1). Approximate IC50 values were 10 µM (ACCase2) and 50 µM (ACCase1) for both CoA esters. Citrate concentrations up to 1 mM had no effect on ACCase1 activity. Above this concentration, citrate was inhibitory. ACCase2 activity was slightly stimulated by citrate over a broad concentration range (0.25–10 mM). The significance of possible effects of acyl-CoAs or citrate in vivo is discussed.


2022 ◽  
Author(s):  
Sahila Beegum ◽  
P J Jainet ◽  
Dawn Emil ◽  
K P Sudheer ◽  
Saurav Das

Abstract Soil pore water pressure analysis is crucial for understanding landslide initiation and prediction. However, field-scale transient pore water pressure measurements are complex. This study investigates the integrated application of simulation models (HYDRUS-2D/3D and GeoStudio–Slope/W) to analyze pore water pressure-induced landslides. The proposed methodology is illustrated and validated using a case study (landslide in India, 2018). Model simulated pore water pressure was correlated with the stability of hillslope, and simulation results were found to be co-aligned with the actual landslide that occurred in 2018. Simulations were carried out for natural and modified hill slope geometry in the study area. The volume of water in the hill slope, temporal and spatial evolution of pore water pressure, and factor of safety were analysed. Results indicated higher stability in natural hillslope (factor of safety of 1.243) compared to modified hill slope (factor of safety of 0.946) despite a higher pore water pressure in the natural hillslope. The study demonstrates the integrated applicability of the physics-based models in analyzing the stability of hill slopes under varying pore water pressure and hill slope geometry and its accuracy in predicting future landslides.


1981 ◽  
Vol 240 (3) ◽  
pp. E279-E285
Author(s):  
S. B. Smith ◽  
R. A. Freedland

Isolated liver parenchymal cells from rats fed a 65% sucrose diet for 14 days were incubated in the presence and absence of 10(-6) M glucagon. The pyruvate kinase obtained from homogenates of the glucagon-treated cells displayed and increased Ks 0.5 for phosphoenolpyruvate (P-enolpyruvate), as well as an increased Ka 0.5 for 6-phosphogluconate (6-P-gluconate), compared to pyruvate kinase from untreated cells. Additionally, glucagon treatment decreased the maximal stimulation of pyruvate kinase by 6-P-gluconate by approximately two-thirds and decreased the Hill coefficient value of pyruvate kinase for 6-P-gluconate from 1.76 to 1.56. 6-Aminonicotinamide, an inhibitor of 6-P-gluconate dehydrogenase, increased 6-P-gluconate levels in isolated liver parenchymal cells three- to sevenfold, depending on the substrates present. The flux of P-enolpyruvate through pyruvate kinase was increased from 18 to 40% in these preparations and was highly correlated with the increase in 6-P-gluconate levels. The results suggest that 6-P-gluconate could regulate pyruvate kinase activity in the intact liver parenchymal cell. Furthermore, the activator would be of greatest importance in the lipogenic animal.


2015 ◽  
Vol 145 (6) ◽  
pp. 555-563 ◽  
Author(s):  
Silvia Ravera ◽  
Matthias Quick ◽  
Juan P. Nicola ◽  
Nancy Carrasco ◽  
L. Mario Amzel

Prokaryotic and eukaryotic Na+-driven transporters couple the movement of one or more Na+ ions down their electrochemical gradient to the active transport of a variety of solutes. When more than one Na+ is involved, Na+-binding data are usually analyzed using the Hill equation with a non-integer exponent n. The results of this analysis are an overall Kd-like constant equal to the concentration of ligand that produces half saturation and n, a measure of cooperativity. This information is usually insufficient to provide the basis for mechanistic models. In the case of transport using two Na+ ions, an n < 2 indicates that molecules with only one of the two sites occupied are present at low saturation. Here, we propose a new way of analyzing Na+-binding data for the case of two Na+ ions that, by taking into account binding to individual sites, provides far more information than can be obtained by using the Hill equation with a non-integer coefficient: it yields pairs of possible values for the Na+ affinities of the individual sites that can only vary within narrowly bounded ranges. To illustrate the advantages of the method, we present experimental scintillation proximity assay (SPA) data on binding of Na+ to the Na+/I− symporter (NIS). SPA is a method widely used to study the binding of Na+ to Na+-driven transporters. NIS is the key plasma membrane protein that mediates active I− transport in the thyroid gland, the first step in the biosynthesis of the thyroid hormones, of which iodine is an essential constituent. NIS activity is electrogenic, with a 2:1 Na+/I− transport stoichiometry. The formalism proposed here is general and can be used to analyze data on other proteins with two binding sites for the same substrate.


Author(s):  
Benjamin C. Fortune ◽  
Lachlan R. McKenzie ◽  
Logan T. Chatfield ◽  
Christopher G. Pretty

Abstract This paper presents a method to estimate the individual component values of a bipolar electrode-skin interface, with future intent of applying compensatory electrode-skin impedance balancing prior recording bio-signals with electromyography. The electrode-skin interface was stimulated by a step input and the output behaviour was characterised using a single exponential model per electrode. The method was applied to simulated circuitry, passive component circuitry and a human subject. The accuracy of the method was determined using the known values that comprised the simulated and passive component circuitry. Nine of ten simulated data sets resulted in accurate estimations, with a maximum error of 0.763% and a mean error of 0.076% per component. The method also produced successful estimates for nine of the ten physical circuitry data sets, with a maximum error of 10.2% and a mean error of 3.49% per component. The method was unsuccessful in estimating the individual electrode-skin impedance components for the human subject: this was due to the system failing to reach steady state during the stimulation period. The authors suspect a DC offset caused by the half-cell potentials associated with the electrode-skin interface were the cause of the unexpected behaviour.


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