Please answer as soon as possible!! * Can you please check if the answer below has correct information/is answered correctly:  The Warburg effect is a phenomenon observed in cancer cells where they show an increased rate of glycolysis even under aerobic conditions. The normal cellular energy production pathway involves glycolysis in the cytoplasm, which is then followed by oxidative phosphorylation in the mitochondria. But in cancer cells that are undergoing the Warburg effect even in the presence of oxygen, there is a shift toward reliance on glycolysis for energy production.   Key Changes in Carbohydrate Pathways: High Glucose Transporter Expression: Cancer cells can be seen with an increased expression of glucose transporters, which facilitate the uptake of glucose from the extracellular environment. High Hexokinase, Expression: Hexokinase is an enzyme that phosphorylates glucose, which traps it inside the cell. Cancer cells often overexpress hexokinase so, it’s promoting the entry of glucose into glycolysis.   High PKM2 Expression: PKM2 is an isoform of pyruvate kinase that is a key enzyme in glycolysis. PKM2 expression is upregulated in cancer cells giving influence to the glycolytic flux.   High PDK Levels: PDK inhibits pyruvate dehydrogenase and redirects pyruvate away from entering the mitochondria for oxidative phosphorylation which results in further favoring glycolysis.   High Expression of Specific Transcription Factors: Transcription factors such as MYC, HIF-1α, NF-κB, and OCT1 are upregulated a promotion to the Warburg effect by influencing the expression of genes involved in glycolysis. B. Pyruvate kinase is a critical enzyme in glycolysis that catalyzes the conversion of phosphoenolpyruvate to pyruvate which produces ATP. In the Warburg effect, the M2 isoform of PKM2 is often overexpressed in cancer cells.   Role of PKM2 in the Warburg Effect:   - PKM2 Expression: Cancer cells show increased expression of PKM2, which has lower enzymatic activity compared to other isoforms. This reduced activity contributes to the accumulation of glycolytic intermediates, supporting anabolic pathways for cell proliferation. - Promotion of Anabolic Metabolism: The less active PKM2 diverts glycolytic intermediates toward biosynthetic pathways, promoting the synthesis of macromolecules needed for cell growth and proliferation.   - Adaptation to Energy Demands: While the Warburg effect seems less efficient in terms of ATP production, the altered PKM2 activity allows cancer cells to balance ATP production with the production of biomass required for rapid cell division.   Role of MYC/HIF in Signal Transduction and Effects on Pyruvate:   Increase in Activity of MYC/HIF:   - MYC and HIF Activation: MYC and HIF (Hypoxia-Inducible Factor) are transcription factors that play crucial roles in cell survival, proliferation, and metabolism. They are often upregulated in cancer cells.   - Maximized Transcription: The Activated MYC and HIF stimulate the transcription of genes involved in glycolysis, including those encoding glucose transporters, hexokinase, and pyruvate kinase.   - Enhanced Glycolytic Flux: The increased expression of glycolytic enzymes, including PKM2, under the influence of MYC and HIF, promotes a higher glycolytic flux in cancer cells.   - Shift in Pyruvate Fate: HIF also induces the expression of PDK, which inhibits pyruvate dehydrogenase. This event leads to converting pyruvate to lactate in the cytoplasm instead of entering the mitochondria for oxidative phosphorylation.   -Adaptation to Hypoxic Conditions: HIF activation by hypoxia promotes glycolysis, allowing cells to adapt to low oxygen conditions by utilizing an alternative pathway for energy production.  This is the question: Describe the Warburg effect with respect to all carbohydrate pathways involved. Explain how the changes in the expression of PMK2 contributes to the Warburg Effect.  Describe how an increase in activity of MYC/HIF might occur and how that effects the outcome of Pyruvate.

Human Physiology: From Cells to Systems (MindTap Course List)
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ISBN:9781285866932
Author:Lauralee Sherwood
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Chapter2: Cell Physiology
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Problem 10RE: Using the answer code on the right, indicate which form of energy production is being described: 1....
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*Please answer as soon as possible!! * Can you please check if the answer below has correct information/is answered correctly: 

  1. The Warburg effect is a phenomenon observed in cancer cells where they show an increased rate of glycolysis even under aerobic conditions. The normal cellular energy production pathway involves glycolysis in the cytoplasm, which is then followed by oxidative phosphorylation in the mitochondria. But in cancer cells that are undergoing the Warburg effect even in the presence of oxygen, there is a shift toward reliance on glycolysis for energy production.

 

  • Key Changes in Carbohydrate Pathways:
  1. High Glucose Transporter Expression: Cancer cells can be seen with an increased expression of glucose transporters, which facilitate the uptake of glucose from the extracellular environment.
  2. High Hexokinase, Expression: Hexokinase is an enzyme that phosphorylates glucose, which traps it inside the cell. Cancer cells often overexpress hexokinase so, it’s promoting the entry of glucose into glycolysis.

 

  1. High PKM2 Expression: PKM2 is an isoform of pyruvate kinase that is a key enzyme in glycolysis. PKM2 expression is upregulated in cancer cells giving influence to the glycolytic flux.

 

  1. High PDK Levels: PDK inhibits pyruvate dehydrogenase and redirects pyruvate away from entering the mitochondria for oxidative phosphorylation which results in further favoring glycolysis.

 

  1. High Expression of Specific Transcription Factors: Transcription factors such as MYC, HIF-1α, NF-κB, and OCT1 are upregulated a promotion to the Warburg effect by influencing the expression of genes involved in glycolysis.



B.

Pyruvate kinase is a critical enzyme in glycolysis that catalyzes the conversion of phosphoenolpyruvate to pyruvate which produces ATP. In the Warburg effect, the M2 isoform of PKM2 is often overexpressed in cancer cells.

 

  • Role of PKM2 in the Warburg Effect:

 

- PKM2 Expression: Cancer cells show increased expression of PKM2, which has lower enzymatic activity compared to other isoforms. This reduced activity contributes to the accumulation of glycolytic intermediates, supporting anabolic pathways for cell proliferation.

- Promotion of Anabolic Metabolism: The less active PKM2 diverts glycolytic intermediates toward biosynthetic pathways, promoting the synthesis of macromolecules needed for cell growth and proliferation.

 

- Adaptation to Energy Demands: While the Warburg effect seems less efficient in terms of ATP production, the altered PKM2 activity allows cancer cells to balance ATP production with the production of biomass required for rapid cell division.

 

  1. Role of MYC/HIF in Signal Transduction and Effects on Pyruvate:

 

  • Increase in Activity of MYC/HIF:

 

- MYC and HIF Activation: MYC and HIF (Hypoxia-Inducible Factor) are transcription factors that play crucial roles in cell survival, proliferation, and metabolism. They are often upregulated in cancer cells.

 

- Maximized Transcription: The Activated MYC and HIF stimulate the transcription of genes involved in glycolysis, including those encoding glucose transporters, hexokinase, and pyruvate kinase.

 

- Enhanced Glycolytic Flux: The increased expression of glycolytic enzymes, including PKM2, under the influence of MYC and HIF, promotes a higher glycolytic flux in cancer cells.

 

- Shift in Pyruvate Fate: HIF also induces the expression of PDK, which inhibits pyruvate dehydrogenase. This event leads to converting pyruvate to lactate in the cytoplasm instead of entering the mitochondria for oxidative phosphorylation.

 

-Adaptation to Hypoxic Conditions: HIF activation by hypoxia promotes glycolysis, allowing cells to adapt to low oxygen conditions by utilizing an alternative pathway for energy production. 

This is the question: Describe the Warburg effect with respect to all carbohydrate pathways involved.

Explain how the changes in the expression of PMK2 contributes to the Warburg Effect. 

Describe how an increase in activity of MYC/HIF might occur and how that effects the outcome of Pyruvate.





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