Even in the presence of large amount of oxygen and functionable mitochondria, cancer cells follow anaerobic respiration to generate the ATPs to meet it's energy demand. It sounds like they are wasting the energy comparing to the ATPs generated using aerobic respiration. But why the cancer cells are following this?
There are several possible reasons for this phenomenon which I am mentioning here,
1. It will generate large amount of ATPs within short time. Which will be comparatively same to the quantity of ATPs from aerobic respiration.
2. It does not require cell organelle like mitochondria. Irrespective of the organelle presence, anaerobic respiration occurs and generates energy.
3. It will generate ATPs irrespective of the available oxygen in the cell environment. So it can survive even the place where the blood vessels does not deliver oxygen.
4. Just like during exercise how the muscle cells perform the energy generation through anaerobic respiration in short time. Cancer cells do the same to divide rapidly. Further it create an acidic environment by accumulating pyruvate. This low pH suppress the body immune system to perform it's function effectively.
5. The important point what I consider is, bypassing the TCA cycle will reduce the feedback inhibition of glycolysis by TCA cycle intermediates such as citrate, etc. Even ATPs are allosteric inhibitors to glycolysis by inhibiting the Phospofructokinase-1 enzyme. But creating high energy demand through anerobic respiration, this can be neglected in the cancer cells.
Understanding the cancer biology is always ends in some phenomenon. I added several points about what I think about the reason behind the Warburg effect of cancer cells. I am interested to hear more phenomenon cancer cells do.
Add the ideas and facts about the Warburg effect of cancer cells to make this discussion more interesting.
Warburg effect or aerobic glycolysis cannot be viewed from an energetic point of view. It requires a multimodal approach.
Lets start with a contrafactual analysis. What would happen if a malignant cell would not use aerobic glycolysis.
Proliferation reduces oxygen availability because angiogenesis is quite ineffective to compensate for the increased need of oxygen.
In second place, the production of reactive oxygen species would induce a very dangerous oxidative stress. Warburg effect prevents both.
The main purpose of the Warburg effect is not to provide energy to the cell but to create building blocks for synthesis of amino acids, purine and pyrimidine precursors, and antioxidative molecules.
The energy imbalance is compensated by two mechanisms:
1) Increase of the glycolytic flux with a glucose uptake that increases 10-17 folds.
2) The oxidative metabolism may be downregulated but it is not eliminated.
Furthermore, during Warburg effect, almost 50% of glucose can be metabolized through the OXPHOS pathway.
Tumor cells need to keep the Krebs cycle working.
Therefore, the idea that malignant cells use the glycolytic pathway exclusively without OXPHOS is a well established mistake since the Warburg days.
Hi Balaji B,
I believe all cells switch to purely glycolytic means for energy production during cellular division, to decrease mutations during DNA replication. Normally all cells (not just cancer cells) increase their internal pH to a value of about 7.5-7.65 from 7.2 when a cell is about to divide. This decreases spontaneous mutational events like spontaneous base deaminations, which are favored under more acidic conditions. The switch to glycolysis seems to be tied into this, as the mitochondrion is the major source of ROS and these too cause DNA damage. I believe this is why our stem cells are housed mainly in the bone marrow which is essentially an hypoxic environment, as this protects their DNA from ROS etc. Normal terminally differentiated tissue cells are essentially non-dividing and therefore don't need to protect their DNA from damage to the same extent.
Just a few thoughts, and good luck with your research.
Phil
El efecto Warburg es un fenómeno metabólico observado en muchas células cancerosas en el cual aumenta la dependencia de la glucólisis aeróbica, que es la vía metabólica que convierte la glucosa en lactato incluso en presencia de oxígeno suficiente para realizar la respiración celular. Aunque la glucólisis aeróbica es menos eficiente en términos de producción de energía en comparación con la respiración celular completa, las células cancerosas muestran una mayor preferencia por este mecanismo metabólico. A continuación, se describen algunas formas en las que el efecto Warburg beneficia a las células cancerosas:
Si bien el efecto Warburg es un rasgo metabólico comúnmente observado en células cancerosas, es importante tener en cuenta que no todos los tumores presentan este fenómeno de manera uniforme. La plasticidad metabólica de las células cancerosas les permite adaptarse a diferentes condiciones metabólicas y aprovechar diferentes rutas metabólicas según las necesidades del entorno tumora
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