Podcast
Questions and Answers
What is the primary purpose of regulating metabolic pathways?
What is the primary purpose of regulating metabolic pathways?
Which statement best describes feedback inhibition in metabolic pathways?
Which statement best describes feedback inhibition in metabolic pathways?
What does the Control Coefficient (C_EJ) measure in metabolic pathways?
What does the Control Coefficient (C_EJ) measure in metabolic pathways?
What does a high Control Coefficient (C_EJ) indicate about enzyme activity changes?
What does a high Control Coefficient (C_EJ) indicate about enzyme activity changes?
Signup and view all the answers
What does the Elasticity Coefficient (ε) measure in metabolic regulation?
What does the Elasticity Coefficient (ε) measure in metabolic regulation?
Signup and view all the answers
What is the primary factor for the control of ethanol production in yeast?
What is the primary factor for the control of ethanol production in yeast?
Signup and view all the answers
How does feedback inhibition function in metabolic pathways?
How does feedback inhibition function in metabolic pathways?
Signup and view all the answers
What does the Summation Theorem state about the Control Coefficient in a metabolic pathway?
What does the Summation Theorem state about the Control Coefficient in a metabolic pathway?
Signup and view all the answers
In what environmental conditions does Rubisco present a high control coefficient?
In what environmental conditions does Rubisco present a high control coefficient?
Signup and view all the answers
Which enzyme is identified as a critical control point in cancer cells during glycolysis?
Which enzyme is identified as a critical control point in cancer cells during glycolysis?
Signup and view all the answers
What happens to the enzyme activity during aerobic glycolysis in cancer cells?
What happens to the enzyme activity during aerobic glycolysis in cancer cells?
Signup and view all the answers
What characterizes the Connectivity Theorem in metabolic pathways?
What characterizes the Connectivity Theorem in metabolic pathways?
Signup and view all the answers
Why are high Control Coefficient enzymes considered ideal drug targets in diseases?
Why are high Control Coefficient enzymes considered ideal drug targets in diseases?
Signup and view all the answers
Study Notes
Metabolic Pathway Regulation
- Metabolic pathways are regulated to maintain homeostasis (steady state of metabolites).
- Pathway regulation adapts to:
- Increased glycolysis during action.
- Decreased glycolysis after action.
- Feedback Inhibition: End products inhibit upstream steps (e.g., ATP inhibits phosphofructokinase in glycolysis).
Feedback Inhibition
- End products of a pathway inhibit enzymes earlier in the pathway, like ATP inhibiting phosphofructokinase in glycolysis.
Flux Control Analysis (FCA)
- Flux refers to the rate of metabolite flow through a pathway.
- Control Coefficient (CEJ):
- Measures the effect of an enzyme's activity change (ΔVE) on the overall pathway flux (J).
- CEJ = [(ΔJ/J)]/[(ΔVE/VE)] – a fractional value, without units.
- High CEJ indicates that small enzyme activity changes have large flux effects.
- Summation Theorem: The total CEJ for all enzymes in a pathway equals 1.
- High CEJ enzymes are key bottlenecks and ideal drug targets in diseases (e.g., GAPDH in cancer).
Connectivity and Elasticity
- Elasticity Coefficient (ε): Measures local sensitivity of an enzyme to substrate/product concentration changes.
- Connectivity Theorem: In vivo changes in one enzyme's activity ripple across the pathway, affecting others.
Examples of FCA in Action
- Ethanol Production in Yeast: Control resides in glucose uptake (CJperm = 1.21). Changing other enzymes (e.g., hexokinase, PFK) has minimal impact on ethanol production.
- Photosynthesis and Rubisco: Rubisco's control depends on environmental conditions: High light/CO2: Rubisco's CEJ is high as it becomes a bottleneck; Low light/CO2: Control shifts to other steps.
- Glycolysis in Cancer (Warburg Effect): Cancer cells prioritize aerobic glycolysis. GAPDH: CEJ increases significantly in cancer cells, making it a critical control point. Targeting GAPDH with inhibitors (e.g., Koningic Acid) disrupts glycolysis in cancer cells but minimally affects healthy cells (low GAPDH CEJ).
Key Takeaways
- Regulation ensures metabolic responsiveness but does not always equate to control.
- FCA demonstrates the distribution of control among pathway enzymes and its dependence on conditions.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Test your understanding of metabolic pathway regulation, including feedback inhibition and flux control analysis. Explore how enzymes and metabolites interact to maintain homeostasis in the body, and understand key concepts like the control coefficient and the Summation Theorem.
