TITLE

A kinetic-metabolic model based on cell energetic state: study of CHO cell behavior under Na-butyrate stimulation

AUTHOR(S)
Ghorbaniaghdam, Atefeh; Henry, Olivier; Jolicoeur, Mario
PUB. DATE
April 2013
SOURCE
Bioprocess & Biosystems Engineering;Apr2013, Vol. 36 Issue 4, p469
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
A kinetic-metabolic model approach describing and simulating Chinese hamster ovary (CHO) cell behavior is presented. The model includes glycolysis, pentose phosphate pathway, TCA cycle, respiratory chain, redox state and energetic metabolism. Growth kinetic is defined as a function of the major precursors for the synthesis of cell building blocks. Michaelis-Menten type kinetic is used for metabolic intermediates as well as for regulatory functions from energy shuttles (ATP/ADP) and cofactors (NAD/H and NADP/H). Model structure and parameters were first calibrated using results from bioreactor cultures of CHO cells expressing recombinant t-PA. It is shown that the model can simulate experimental data for all available experimental data, such as extracellular glucose, glutamine, lactate and ammonium concentration time profiles, as well as cell energetic state. A sensitivity analysis allowed identifying the most sensitive parameters. The model was then shown to be readily adaptable for studying the effect of sodium butyrate on CHO cells metabolism, where it was applied to the cases with sodium butyrate addition either at mid-exponential growth phase (48 h) or at the early plateau phase (74 h). In both cases, a global optimization routine was used for the simultaneous estimation of the most sensitive parameters, while the insensitive parameters were considered as constants. Finally, confidence intervals for the estimated parameters were calculated. Results presented here further substantiate our previous findings that butyrate treatment at mid-exponential phase may cause a shift in cellular metabolism toward a sustained and increased efficiency of glucose utilization channeled through the TCA cycle.
ACCESSION #
86051709

 

Related Articles

  • Neopterin inhibits ATP-induced calcium release in alveolar epithelial cells in vitro. Hoffmann, Georg; Gollnick, Frank; Meyer, Rainer // Mediators of Inflammation;Jun2002, Vol. 11 Issue 3, p181 

    Background: Serum neopterin concentrations rise during activation of the cellular immune system. It is suggested that neopterin interacts with cellular redox mechanisms. This induces oxidative stress, which inhibits intracellular Ca[sup 2+] transients in various cell types. In type II alveolar...

  • H±nmdash;ATPases in Oxidative and Photosynthetic Phosphorylation. McCarty, Richard E. // BioScience;Jan1985, Vol. 35 Issue 1, p27 

    The H[sup +]-ATPases of mitochondria, chloroplasts, and bacteria are complex enzymes that couple the synthesis and hydrolysis of adenosine 5'-triphosphate to transmembrane fluxes of protons. In both structure and chemical mechanism, this class of enzymes differs markedly from the...

  • Redox, haem and CO in enzymatic catalysis and regulation. Ragsdale, Stephen W.; Li Yi; Bender, G�nes; Gupta, Nirupama; Yan Kung; Lifen Yan; Stich, Troy A.; Doukov, Tzanko; Leichert, Lars; Jenkins, Paul M.; Bianchetti, Christopher M.; George, Simon J.; Cramer, Stephen P.; Britt, R. David; Jakob, Ursula; Martens, Jeffrey R.; Phillips Jr, George N.; Drennan, Catherine L. // Biochemical Society Symposia;Jun2012, Vol. 40 Issue 3, p501 

    The present paper describes general principles of redox catalysis and redox regulation in two diverse systems. The first is microbial metabolism of CO by the Wood--Ljungdahl pathway, which involves the conversion of CO or H2/CO2 into acetyl-CoA, which then serves as a source of ATP and cell...

  • Antioxidant activities of dithiol alpha-lipoic acid. Islam, M. T. // Bangladesh Journal of Medical Science;Jun2009, Vol. 8 Issue 3, p6 

    Alpha-lipoic acid, a dithiol compound derived from octanoic acid, which acts as a coenzyme for several redox reactions in almost all the tissue of the body. It retains its protective functions in both oxidized and reduced forms. Alpha-lipoic acid reduces oxidative stress by redox generation of...

  • Advanced Glycation Endproducts Induce Changes in Glucose Consumption, Lactate Production, and ATP Levels in SH-SY5Y Neuroblastoma Cells by a Redox-Sensitive Mechanism. Susana Garcia de Arriba // Journal of Cerebral Blood Flow & Metabolism;Nov2003, Vol. 23 Issue 11, p1307 

    SUMMARY: Advanced glycation endproducts (AGEs) accumulate on long-lived proteins, including β-amyloid plaques in Alzheimer's disease, and are suggested to contribute to neuronal dysfunction and cell death. We have investigated the effects of a model AGE upon glucose metabolism and energy...

  • Exercise-mediated alteration of protein redox states in plasma: a possible stimulant for hormetic response. Poon, H. F.; Shreve, N. A.; Veicsteinas, A.; Calabrese, V.; Esposito, F.; Butterfield, D. A. // Sport Sciences for Health;Dec2007, Vol. 2 Issue 2, p76 

    Physical exercise increases the metabolic rate and production of reactive oxygen species subsequent to elevated oxidative phosphorylation required to meet the higher ATP demand. This increased free radical generation could alter the redox state of proteins. In order to gain insight into the...

  • Avian UCP: The Killjoy in the Evolution of the Mitochondrial Uncoupling Proteins. Emre, Yalin; Hurtaud, Corinne; Ricquier, Daniel; Bouillaud, Frederic; Hughes, Joseph; Criscuolo, François // Journal of Molecular Evolution;Oct2007, Vol. 65 Issue 4, p392 

    The understanding of mitochondrial functioning is of prime importance since it combines the production of energy as adenosine triphosphate (ATP) with an efficient chain of redox reactions, but also with the unavoidable production of reactive oxygen species (ROS) involved in aging. Mitochondrial...

  • Genetic inactivation of mitochondria-targeted redox enzyme p66ShcA preserves neuronal viability and mitochondrial integrity in response to oxidative challenges. Su, Kimmy; Bourdette, Dennis; Forte, Michael // Frontiers in Physiology;Jun2012, Vol. 3, p1 

    Mitochondria are essential to neuronal viability and function due to their roles in ATP production, intracellular calcium regulation, and activation of apoptotic pathways. Accordingly, mitochondrial dysfunction has been indicated in a wide variety of neurodegenerative diseases, including...

  • Coenzyme Q10: The essential nutrient. Saini, Rajiv // Journal of Pharmacy & Bioallied Sciences;Jul-Sep2011, Vol. 3 Issue 3, p466 

    The article focuses on the importance of the function of the ubiquinone Coenzyme Q-10 (CoQ-10) as an energy transfer molecule in organs with high rates of metabolism including, the heart and the kidney. It notes the role of CoQ-10 in the electron-transport chain during the series of redox...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics