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Al-Husari2013 - pH and lactate in tumor

ABSTRACT: The paper describes a model of pH control in tumor. Created by COPASI 4.26 (Build 213) This model is described in the article: Regulation of tumour intracellular pH: A mathematical model examining the interplay between H and lactate Maymona Al-Husari, Steven D. Webb Journal of Theoretical Biology 322 (2013) 58–71 Abstract: Non-invasive measurements of pH have shown that both tumour and normal cells have intracellular pH (pHi) that lies on the alkaline side of neutrality (7.1–7.2). However, extracellular pH (pHe) is reported to be more acidic in some tumours compared to normal tissues. Many cellular processes and therapeutic agents are known to be tightly pH dependent which makes the study of intracellular pH regulation of paramount importance. We develop a mathematical model that examines the role of various membrane-based ion transporters in tumour pH regulation, in particular, with a focus on the interplay between lactate and H ions and whether the lactate/H symporter activity is sufficient to give rise to the observed reversed pH gradient that is seen is some tumours. Using linear stability analysis and H ions. We extend this analysis using perturbation techniques to specifically examine a rapid change in H-ion concentrations relative to variations in lactate. We then perform a parameter sensitivity analysis to explore solution robustness to parameter variations. An important result from our study is that a reversed pH gradient is possible in our system but for unrealistic parameter estimates—pointing to the possible involvement of other mechanisms in cellular pH gradient reversal, for example acidic vesicles, lysosomes, golgi and endosomes. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Jinghao Men

PROVIDER: BIOMD0000000805 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000805?filename=Al-Husari2013-biopax2.owl	Owl
	BIOMD0000000805?filename=Al-Husari2013-biopax3.owl	Owl
	BIOMD0000000805?filename=Al-Husari2013-matlab.m	Other
	BIOMD0000000805?filename=Al-Husari2013-octave.m	Other
	BIOMD0000000805?filename=Al-Husari2013.cps	Other

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Regulation of tumour intracellular pH: a mathematical model examining the interplay between H+ and lactate.

Al-Husari Maymona M Webb Steven D SD

Journal of theoretical biology 20130120

Non-invasive measurements of pH have shown that both tumour and normal cells have intracellular pH (pHi) that lies on the alkaline side of neutrality (7.1-7.2). However, extracellular pH (pHe) is reported to be more acidic in some tumours compared to normal tissues. Many cellular processes and therapeutic agents are known to be tightly pH dependent which makes the study of intracellular pH regulation of paramount importance. We develop a mathematical model that examines the role of various membr ...[more]

PMID: 23340437

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