Determining and understanding the control of glycolysis in fast‐growth tumor cells

Marín‐Hernández, Álvaro; Rodrı́guez-Enrı́quez, Sara; Vital-González, Paola A.; Flores-Rodríguez, Fanny L.; Macı́as-Silva, Marina; Sosa-Garrocho, Marcela; Moreno‐Sánchez, Rafael

doi:10.1111/j.1742-4658.2006.05214.x

Cited by 174 publications

(69 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This has been shown experimentally many times [73][74][75][76][77][78][79][80][81][82] as well as being consistent with theory. This cannot be easily disputed.…”

Section: The Phosphofructokinase Paradoxsupporting

confidence: 86%

Control and regulation of pathways via negative feedback

Sauro¹

2017

J. R. Soc. Interface.

View full text Add to dashboard Cite

The biochemical networks found in living organisms include a huge variety of control mechanisms at multiple levels of organization. While the mechanistic and molecular details of many of these control mechanisms are understood, their exact role in driving cellular behaviour is not. For example, yeast glycolysis has been studied for almost 80 years but it is only recently that we have come to understand the systemic role of the multitude of feedback and feed-forward controls that exist in this pathway. In this article, control theory is discussed as an approach to dissect the control logic of complex pathways. One of the key issues is distinguishing between the terms control and regulation and how these concepts are applied to regulated enzymes such as phosphofructokinase. In doing so, one of the paradoxes in metabolic regulation can be resolved where enzymes such as phosphofructokinase have little control but, nevertheless, possess significant regulatory influence.

show abstract

“…This has been shown experimentally many times [73][74][75][76][77][78][79][80][81][82] as well as being consistent with theory. This cannot be easily disputed.…”

Section: The Phosphofructokinase Paradoxsupporting

confidence: 86%

Control and regulation of pathways via negative feedback

Sauro¹

2017

J. R. Soc. Interface.

View full text Add to dashboard Cite

show abstract

“…This metabolite can exhibit a cytosolic concentration between 7 and 25 mM (7,44). We thus tested whether the F16bP-mediated inhibition could also take place in isolated mammalian mitochondria.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Oxidative Phosphorylation Is Regulated by Fructose 1,6-Bisphosphate

Díaz-Ruiz

Avéret

Araiza

et al. 2008

Journal of Biological Chemistry

142

109

View full text Add to dashboard Cite

In numerous cell types, tumoral cells, proliferating cells, bacteria, and yeast, respiration is inhibited when high concentrations of glucose are added to the culture medium. This phenomenon has been named the "Crabtree effect." We used yeast to investigate (i) the short term event(s) associated with the Crabtree effect and (ii) a putative role of hexose phosphates in the inhibition of respiration. Indeed, yeast divide into "Crabtree-positive," where the Crabtree effect occurs, and "Crabtree-negative," where it does not. In mitochondria isolated from these two categories of yeast, we found that low, physiological concentrations of glucose 6-phosphate and fructose 6-phosphate slightly (20%) stimulated the respiratory flux and that this effect was strongly antagonized by fructose 1,6-bisphosphate (F16bP). On the other hand, F16bP by itself was able to inhibit mitochondrial respiration only in mitochondria isolated from a Crabtree-positive strain. Using permeabilized spheroplasts from Crabtree-positive yeast, we have shown that the sole effect observed at physiological concentrations of hexose phosphates is an inhibition of oxidative phosphorylation by F16bP. This F16bP-mediated inhibition was also observed in isolated rat liver mitochondria, extending this process to mammalian cells. From these results and taking into account that F16bP is able to accumulate in the cell cytoplasm, we propose that F16bP regulates oxidative phosphorylation and thus participates in the establishment of the Crabtree effect.

show abstract

“…The rate of glucose transport by GLUT-1 is altered in situations in which the metabolic rate needs to be adjusted, such as in cell division (mitosis and meiosis), differentiation, transformation, and nutrient starvation. Increased GLUT-1 expression correlates with poor survival and poor therapeutic outcomes in cancer [37]. However, the first and rate-limiting enzyme in glycolysis is hexokinase (HK), highly expressed in many tumors, and is responsible for ensuring the necessary energy supply to malignant tumors.…”

Section: Hypoxia Reprogramming Carbohydrate Metabolismmentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

show abstract

Determining and understanding the control of glycolysis in fast‐growth tumor cells

Cited by 174 publications

References 59 publications

Control and regulation of pathways via negative feedback

Control and regulation of pathways via negative feedback

Mitochondrial Oxidative Phosphorylation Is Regulated by Fructose 1,6-Bisphosphate

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Contact Info

Product

Resources

About