A computer program for fitting data to the Michaelis-Menten equation

Hanson, Kenneth R.; Ling, Robert F.; Havir, Evelyn A.

doi:10.1016/0006-291x(67)90586-4

Cited by 141 publications

(42 citation statements)

References 5 publications

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“…Precipitated proteins were cleared by centrifugation, and the inorganic phosphate was determined as described in Fiske and Subbarow (9). Data were analyzed using the Michaelis-Menten equation yielding V max and Km (16,51).…”

Section: Actin-activated Myosin Atpase Activitymentioning

confidence: 99%

Discrete effects of A57G-myosin essential light chain mutation associated with familial hypertrophic cardiomyopathy

Kazmierczak

Paulino

Huang

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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(alanine-to-glycine) mutation in the myosin ventricular essential light chain (ELC) were assessed in vitro and in vivo using previously generated transgenic (Tg) mice expressing A57G-ELC mutant vs. wild-type (WT) of human cardiac ELC and in recombinant A57G-or WT-protein-exchanged porcine cardiac muscle strips. Compared with the Tg-WT, there was a significant increase in the Ca 2ϩ sensitivity of force (⌬pCa50 Х 0.1) and an ϳ1.3-fold decrease in maximal force per cross section of muscle observed in the mutant preparations. In addition, a significant increase in passive tension in response to stretch was monitored in Tg-A57G vs. Tg-WT strips indicating a mutation-induced myocardial stiffness. Consistently, the hearts of Tg-A57G mice demonstrated a high level of fibrosis and hypertrophy manifested by increased heart weight-to-body weight ratios and a decreased number of nuclei indicating an increase in the two-dimensional size of Tg-A57G vs. Tg-WT myocytes. Echocardiography examination showed a phenotype of eccentric hypertrophy in Tg-A57G mice, enhanced left ventricular (LV) cavity dimension without changes in LV posterior/anterior wall thickness. Invasive hemodynamics data revealed significantly increased end-systolic elastance, defined by the slope of the pressure-volume relationship, indicating a mutation-induced increase in cardiac contractility. Our results suggest that the A57G allele causes disease by means of a discrete modulation of myofilament function, increased Ca 2ϩ sensitivity, and decreased maximal tension followed by compensatory hypertrophy and enhanced contractility. These and other contributing factors such as increased myocardial stiffness and fibrosis most likely activate cardiomyopathic signaling pathways leading to pathologic cardiac remodeling. myosin essential light chain; hypertrophic cardiomyopathy; Ca 2ϩ sensitivity of contraction; echocardiography; pressure-volume loops THE BEATING OF THE HEART DEPENDS on ATP-controlled synchronous interactions between two major contractile proteins; myosin and actin (15). The myosin cross bridges are the molecular motors of the heart, which bind and hydrolyze Mg-ATP and cyclically attach and dissociate from actin-tropomyosin (Tm)-troponin (Tn) thin filaments in a Ca 2ϩ -dependent manner. The cycle of Ca 2ϩ fluxes regulate the coupling between excitation and contraction and permit the highly synchronized action of cardiac sarcomeres causing the heart to contract (systole) or relax (diastole) (20). The two key components of the myosin cross bridge include the motor domain, consisting of the ATP and actin binding sites, and the neck domain also called the lever arm, which is structurally supported by two types of myosin light chains, the essential (ELC) and the regulatory (RLC) light chains (44). Attached to their respective IQ motifs on the myosin heavy chain (MHC), both light chains inherently participate in all biochemical steps of the acto-myosin cycle and execution of the power stroke (52). As components of the neck region of myosin, both ELC and RL...

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Section: Actin-activated Myosin Atpase Activitymentioning

confidence: 99%

Discrete effects of A57G-myosin essential light chain mutation associated with familial hypertrophic cardiomyopathy

Kazmierczak

Paulino

Huang

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…The latter method gives convergence rapidly if the primary estimates are sufficiently accurate. It is convenient to write the computer programs so that a print-out of the vector of residuals and the residual sum of squares (6) (6) in addition to the parameter values and their standard errors.…”

Section: Regression Proceduresmentioning

confidence: 99%

“…In simulation studies a model is built to describe the system investigated, whereas in the optimization approach a set of numerical values are determined to give the best fit of a predetermined model to experimental data. The present paper is an attempt to develop and summarize criteria for selection of one of several rival models using the optimization techniques widely applied in steady state kinetics (Johansen and Lumry [2] ; Berman et al [3] ; Bliss and James [4] ; Dammkoehler [5] ; Hanson et al [6] ; Kowalik and Morrison [7] ; Cleland [8,9] ; Reich et al [10]). The selection of the best model is generally performed by rejection of all models, which are considered inappropriate by statistical or physico-chemical criteria.…”

Section: Introductionmentioning

confidence: 99%

A procedure based on statistical criteria for discrimination between steady state kinetic models

Bartfai

Mannervik

1972

FEBS Letters

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“…Illumination obviously caused a change to linearity. The steady state velocity values were used to estimate Km and Vmax values (12).…”

mentioning

confidence: 99%

Changing Kinetic Properties of Fructose-1,6-bisphosphatase from Pea Chloroplasts during Photosynthetic Induction

Marques

Anderson²

1985

Plant Physiol.

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ABSTRACrAfter dark-light transitions, there is a delay in photosynthetic CO2 fixation by isolated pea chloroplasts in the range of some minutes. In order to assess the physiological significance of light modulation of enzyme activity in the control of induction, we made estimates of the kinetic parameters of fructose-1,6-bisphosphatase immediately upon release from pea chloroplasts in the dark and after illumination for various time periods. The Michaelis constant for fructose-1,6-bisphosphate decreased and maximal velocities increased during -induction. It seems likely that light activation of this enzyme is one of the factors contributing to the overcoming of the lag period in photosynthetic CO2 fixation.When isolated chloroplasts are exposed to dark-light transitions, there is a delay in photosynthetic CO2 fixation in the range of minutes. The length of the induction period depends on the incubation medium and on the condition of the chloroplasts (6,7,9,16,20). The question arises whether induction is mainly related to the concentration of stromal intermediates, to the activation of enzymes, or to both (5-7, 16, 17, 20, 21, 23). FruP2ase2 is thought to be one of the controlling enzymes of the reductive pentose phosphate pathway. The regulation of the enzyme activity in vivo has been suggested to be due to lightinduced changes in stromal Mg2+ concentration and pH (14), and to activation (presumably reductive covalent modification) mediated by light (1, 4). In experiments with purified spinach Fru-P2ase, it has been shown that DTT treatment does not change the maximal velocity of the enzyme, but does change the substrate dependence from sigmoidal to Michaelis Menten (5), so that the apparent affinity of the enzyme for both Fru-1,6-P2 and Mg2e is markedly increased. It therefore seemed of interest to determine the effect of light treatment on the kinetic parameters of the enzyme in intact chloroplasts.To assess the physiological significance of light modulation of Fru-P2ase during induction, we measured the kinetic parameters of the enzyme immediately after release from chloroplasts in the dark, at the end of the lag period, and twice during the maximal rate of C02-dependent 02 evolution. The results indicate that the light-effected properties of Fru-P2ase probably affect the increase of the C02-dependent 02 evolution rate during photosynthetic induction in vivo.

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A computer program for fitting data to the Michaelis-Menten equation

Cited by 141 publications

References 5 publications

Discrete effects of A57G-myosin essential light chain mutation associated with familial hypertrophic cardiomyopathy

Discrete effects of A57G-myosin essential light chain mutation associated with familial hypertrophic cardiomyopathy

A procedure based on statistical criteria for discrimination between steady state kinetic models

Changing Kinetic Properties of Fructose-1,6-bisphosphatase from Pea Chloroplasts during Photosynthetic Induction

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