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一种利用酶动力学和配体结合数据测量S形曲线的新方法。

A new approach to the measurement of sigmoid curves with enzyme kinetic and ligand binding data.

作者信息

Bardsley W G, Wright A J

出版信息

J Mol Biol. 1983 Mar 25;165(1):163-82. doi: 10.1016/s0022-2836(83)80248-4.

DOI:10.1016/s0022-2836(83)80248-4
PMID:6842604
Abstract
  1. It is shown that the extent of sigmoidicity in kinetic or binding curves can always be characterized by two parameters, omega and delta, even when substrate inhibition or other causes of deviations from hyperbolic character are present. 2. The parameter omega is defined in such a way as to measure the fraction of the vertical span of the curve that is sigmoid. 3. The parameter delta is defined in such a way as to measure the S-shaped character in the sigmoid region. 4. It is shown that limits exist to the maximum values of omega and delta for degree n : n and so any individual v(S) or y(x) curve can be described as being barely sigmoid or very sigmoid by a comparison of measured omega and delta values with the limiting values. 5. Monte Carlo simulations of 12 kinetic mechanisms and 6 binding models were performed and the probability density functions and cumulative distribution functions for omega and delta were calculated. 6. An empirical study was performed on the delta values required before experimentalists can recognize a set of data points with error as being sigmoid. 7. The probability with which representative kinetic mechanisms or binding schemes give rise to complex curve shape features has been estimated before. Here using the parameters omega and delta, we calculate the conditional probabilities that sigmoid curves can occur in physiological ranges of substrate or ligand concentration and be sufficiently exaggerated to be recognized as S-shaped. 8. It is shown that some mechanisms, e.g. the random bi bi one, are very unlikely to give strongly sigmoid curves. Such exaggerated curves were found to be more typical of simple sequential kinetic schemes and binding models. 9. It is shown that omega and delta values measured experimentally can sometimes be used in model discrimination and fixing the minimum degree of rate equations. 10. A very powerful result is that in saturation functions of order n the maximum height of the curve that can be sigmoid is (n - 1)/n, and a possible evolutionary significance for this is suggested.
摘要
  1. 结果表明,即使存在底物抑制或其他导致偏离双曲线特征的因素,动力学或结合曲线的S形程度总能由两个参数ω和δ来表征。2. 参数ω的定义方式是测量曲线垂直跨度中呈S形的部分所占比例。3. 参数δ的定义方式是测量S形区域的S形特征。4. 结果表明,对于n级反应,ω和δ的最大值存在极限,因此通过将测量得到的ω和δ值与极限值进行比较,任何一条单独的v(S)或y(x)曲线都可被描述为几乎呈S形或非常呈S形。5. 对12种动力学机制和6种结合模型进行了蒙特卡罗模拟,并计算了ω和δ的概率密度函数及累积分布函数。6. 针对实验人员能够将一组带有误差的数据点识别为呈S形之前所需的δ值进行了实证研究。7. 之前已经估计了代表性动力学机制或结合模式产生复杂曲线形状特征的概率。在此,利用参数ω和δ,我们计算了S形曲线在底物或配体浓度的生理范围内出现并充分夸张到可被识别为S形的条件概率。8. 结果表明,某些机制,如随机双底物双产物机制,极不可能产生强烈的S形曲线。发现这种夸张的曲线在简单的顺序动力学机制和结合模型中更为典型。9. 结果表明,实验测量得到的ω和δ值有时可用于模型判别和确定速率方程的最低级数。10. 一个非常有力的结果是,在n级饱和函数中,呈S形的曲线的最大高度为(n - 1)/n,并提出了对此可能的进化意义。

相似文献

1
A new approach to the measurement of sigmoid curves with enzyme kinetic and ligand binding data.一种利用酶动力学和配体结合数据测量S形曲线的新方法。
J Mol Biol. 1983 Mar 25;165(1):163-82. doi: 10.1016/s0022-2836(83)80248-4.
2
Use of the F test for determining the degree of enzyme-kinetic and ligand-binding data. A Monte Carlo simulation study.使用F检验确定酶动力学和配体结合数据的程度。一项蒙特卡罗模拟研究。
Biochem J. 1983 Apr 1;211(1):23-34. doi: 10.1042/bj2110023.
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Deviations from Michaelis-Menten kinetics. The possibility of complicated curves for simple kinetic schemes and the computer fitting of experimental data for acetylcholinesterase, acid phosphatase, adenosine deaminase, arylsulphatase, benzylamine oxidase, chymotrypsin, fumarase, galactose dehydrogenase, beta-galactosidase, lactate dehydrogenase, peroxidase and xanthine oxidase.与米氏动力学的偏差。简单动力学机制出现复杂曲线的可能性以及对乙酰胆碱酯酶、酸性磷酸酶、腺苷脱氨酶、芳基硫酸酯酶、苄胺氧化酶、胰凝乳蛋白酶、延胡索酸酶、半乳糖脱氢酶、β-半乳糖苷酶、乳酸脱氢酶、过氧化物酶和黄嘌呤氧化酶的实验数据进行计算机拟合。
Biochem J. 1980 Jun 1;187(3):739-65. doi: 10.1042/bj1870739.
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Inhibition of enzyme-catalysed reactions by excess substrate. A theoretical and Monte Carlo study of turning points in v(S) graphs.过量底物对酶催化反应的抑制作用。v(S)图中转折点的理论与蒙特卡罗研究。
J Mol Biol. 1983 Sep 15;169(2):597-617. doi: 10.1016/s0022-2836(83)80066-7.
5
Curves of ligand binding. The use of hyperbolic functions for expressing titration curves.配体结合曲线。使用双曲线函数来表达滴定曲线。
Biochem J. 1974 Mar;137(3):443-7. doi: 10.1042/bj1370443.
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The probability that complex enzyme kinetic curves can be caused by activators of inhibitors.由激活剂或抑制剂引起复杂酶动力学曲线的可能性。
Biochem J. 1981 Jun 1;195(3):589-601. doi: 10.1042/bj1950589.
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Deviations from Michaelis-Menten kinetics. Computation of the probabilities of obtaining complex curves from simple kinetic schemes.偏离米氏动力学。从简单动力学机制计算获得复杂曲线的概率。
Biochem J. 1981 Jan 1;193(1):339-52. doi: 10.1042/bj1930339.
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Rates of reactions catalysed by a dimeric enzyme. Effects of the reaction scheme and the kinetic parameters on co-operativity.二聚体酶催化的反应速率。反应机制和动力学参数对协同性的影响。
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Applications of Monte Carlo Simulation in Modelling of Biochemical Processes蒙特卡罗模拟在生化过程建模中的应用
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[Specific ligand induced dimerization of allosteric enzymes].[特定配体诱导变构酶的二聚化]
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