Chance1960_Glycolysis_Respiration

This model is described inthe article:
Metabolic control mechanisms. 5. A solution for the equations representing interaction between glycolysis and respiration in ascites tumor cells.

Britton Chance, David Garfinkel, Joseph Higgins and Benno Hess, J Biol Chem.
1960 35:2426-2439. PubmedID: 13692276

Abstract:
The other papers of this series present experimental
evidence for possible relationships between the kinetics of oxygen,
glucose, adenosine diphosphate, adenosine triphosphate, and
phosphate and those of the cytochromes and pyridine nucleotides
of the ascites tumor cell. From these general experiments we
are able to formulate, under the law of mass action, a minimum
hypothesis under which the four metabolic regulations previously
described can be observed. In brief, the system can be represented by the known enzyme systems, a relatively higher ADP affinity in respiration than in glycolysis, the mitochondrial membrane, a segregation of ATP into two compartments, and an ATP-utilizing system that is responsive to small decreases of the intracellular ADP level. The chemical equations for the pathway from glucose to oxygen are solved by a digital computer method so that the responses of the chemical equations and of the living cell can be accurately compared.
For reasons already described, we greatly prefer a com-
puter representation based upon a physical or chemical law
representing the action of the system to a model simulating the
operation of the chemical system but not based upon funda-
mental laws for the reactions involved; such a representation
would not adequately represent the kinetics of the system, as in
an electric circuit network or in some types of hydraulic ana-
logues.
The model gives solutions of the reaction kinetics for three types of metabolism: 0 - 64s, metabolism of endogenous substrate
64s - 119s, metabolism of added glucose, illustrating the activated and inhibited aspects of glucose metabolism
119s - 153s, relief of glucose and oxygen inhibition by the addition of an uncoupling agent

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

本模型源自以下论文：
代谢控制机制 第五篇：腹水肿瘤细胞糖酵解与呼吸作用相互作用方程的求解方法
Britton Chance、David Garfinkel、Joseph Higgins与Benno Hess，《生物化学杂志》（Journal of Biological Chemistry），1960年，35卷：2426-2439。PubMed ID：13692276

摘要：
本系列其余论文已通过实验证实，腹水肿瘤细胞内氧气、葡萄糖、二磷酸腺苷（adenosine diphosphate, ADP）、三磷酸腺苷（adenosine triphosphate, ATP）与磷酸盐的动力学变化，同细胞色素和吡啶核苷酸的动力学变化之间存在潜在关联。基于上述一般性实验结果，我们可依据质量作用定律构建最简假说，该假说可复现此前报道的四类代谢调控现象。简言之，该代谢系统可通过以下要素表征：已知的酶促系统、呼吸作用相较于糖酵解对二磷酸腺苷（ADP）具有更高的结合亲和力、线粒体膜、三磷酸腺苷（ATP）的双隔间分隔机制，以及可响应细胞内ADP水平小幅下降的ATP消耗系统。
本研究采用数字计算机方法求解了葡萄糖到氧气的代谢通路对应的化学方程，从而可精准对比理论化学模型与活体细胞的动力学响应。

如前文所述，相较于仅模拟化学系统运行却未基于反应基本定律的模型（如电路网络或部分液压类比模型），我们更倾向于采用基于描述系统行为的物理或化学定律构建的计算机模型——此类模型无法充分复现该系统的动力学特性。

本模型针对三类代谢场景求解了反应动力学方程：
- 0~64秒：内源性底物代谢
- 64~119秒：外源性葡萄糖代谢，该阶段可展示葡萄糖代谢的激活与抑制特征
- 119~153秒：通过添加解偶联剂解除葡萄糖与氧气的抑制效应

本模型源自生物模型数据库（BioModels Database，http://www.ebi.ac.uk/biomodels/），版权归2005-2011年BioModels.net团队所有。更多信息请参阅使用条款。
引用生物模型数据库时，请采用如下著录方式：Li C、Donizelli M、Rodriguez N、Dharuri H、Endler L、Chelliah V、Li L、He E、Henry A、Stefan MI、Snoep JL、Hucka M、Le Novère N、Laibe C（2010）《生物模型数据库：面向已发表定量动力学模型的增强型经人工审定与注释资源》，BMC系统生物学，4卷：92页。