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Questions and Answers
What is the primary role of the Citric Acid Cycle in cellular metabolism?
What is the primary role of the Citric Acid Cycle in cellular metabolism?
Why does the Citric Acid Cycle not occur anaerobically, even though oxygen is not directly involved in the cycle's reactions?
Why does the Citric Acid Cycle not occur anaerobically, even though oxygen is not directly involved in the cycle's reactions?
Which of the following fuel types can be oxidized by the Citric Acid Cycle after conversion to Acetyl-CoA?
Which of the following fuel types can be oxidized by the Citric Acid Cycle after conversion to Acetyl-CoA?
What primarily controls the rate or activity of the Citric Acid Cycle?
What primarily controls the rate or activity of the Citric Acid Cycle?
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Which enzyme of the TCA cycle is the major control enzyme?
Which enzyme of the TCA cycle is the major control enzyme?
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What inhibits isocitrate dehydrogenase?
What inhibits isocitrate dehydrogenase?
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α-Ketoglutarate dehydrogenase requires which of the following?
α-Ketoglutarate dehydrogenase requires which of the following?
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Approximately what percentage of available energy is lost as heat during catabolism?
Approximately what percentage of available energy is lost as heat during catabolism?
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Which enzyme catalyzes the substrate-level phosphorylation of GDP to GTP within the citric acid cycle?
Which enzyme catalyzes the substrate-level phosphorylation of GDP to GTP within the citric acid cycle?
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Besides its role in the citric acid cycle, succinate dehydrogenase also functions as what?
Besides its role in the citric acid cycle, succinate dehydrogenase also functions as what?
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What two substrates are condensed by citrate synthase to form citrate?
What two substrates are condensed by citrate synthase to form citrate?
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Which of the following is the primary source of electrons that feed into the electron transport chain?
Which of the following is the primary source of electrons that feed into the electron transport chain?
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What accepts electrons directly from NADH in the electron transport chain?
What accepts electrons directly from NADH in the electron transport chain?
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What is the final electron acceptor in the electron transport chain?
What is the final electron acceptor in the electron transport chain?
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Which of the following is the correct order of electron carriers in the electron transport chain?
Which of the following is the correct order of electron carriers in the electron transport chain?
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What is the approximate free energy change ($\Delta G$) when FADH2 is oxidized in the electron transport chain?
What is the approximate free energy change ($\Delta G$) when FADH2 is oxidized in the electron transport chain?
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What is the primary role of the proton gradient generated by the electron transport chain (ETC)?
What is the primary role of the proton gradient generated by the electron transport chain (ETC)?
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Which complexes within the electron transport chain directly contribute to the translocation of protons across the inner mitochondrial membrane?
Which complexes within the electron transport chain directly contribute to the translocation of protons across the inner mitochondrial membrane?
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How many ATP molecules are typically generated by F1F0 ATP synthase when an FADH2 molecule is oxidized in the electron transport chain?
How many ATP molecules are typically generated by F1F0 ATP synthase when an FADH2 molecule is oxidized in the electron transport chain?
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What is the primary mechanism by which cyanide inhibits cellular respiration and oxidative phosphorylation?
What is the primary mechanism by which cyanide inhibits cellular respiration and oxidative phosphorylation?
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Inhibition of the electron transport chain leads to several metabolic changes. Which of the following is a direct consequence of this inhibition?
Inhibition of the electron transport chain leads to several metabolic changes. Which of the following is a direct consequence of this inhibition?
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Carbon monoxide (CO) poisoning shares some similarities with cyanide poisoning in its effects on cellular respiration, but also has distinct characteristics. Which of the following is a unique feature of carbon monoxide's mechanism of toxicity?
Carbon monoxide (CO) poisoning shares some similarities with cyanide poisoning in its effects on cellular respiration, but also has distinct characteristics. Which of the following is a unique feature of carbon monoxide's mechanism of toxicity?
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What is the effect of opening proton channels in the mitochondrial inner membrane?
What is the effect of opening proton channels in the mitochondrial inner membrane?
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Which of the following is the correct order of the molecules and complexes involved in the proton gradient creation?
Which of the following is the correct order of the molecules and complexes involved in the proton gradient creation?
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What is the primary effect of uncouplers on ATP synthesis and oxygen consumption?
What is the primary effect of uncouplers on ATP synthesis and oxygen consumption?
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How does brown adipose tissue contribute to thermogenesis in newborns?
How does brown adipose tissue contribute to thermogenesis in newborns?
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Which of the following is NOT a described effect of bacterial toxins acting as indirect uncouplers?
Which of the following is NOT a described effect of bacterial toxins acting as indirect uncouplers?
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What is the function of the NADH shuttle system related to glycolysis?
What is the function of the NADH shuttle system related to glycolysis?
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What is the consequence of pore-forming toxins on mitochondrial function?
What is the consequence of pore-forming toxins on mitochondrial function?
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Why are bacterial toxins described in the content as indirect uncouplers of the respiratory chain?
Why are bacterial toxins described in the content as indirect uncouplers of the respiratory chain?
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Which of the following is a physiological response in adults when exposed to cold temperatures, which is different from the response in babies?
Which of the following is a physiological response in adults when exposed to cold temperatures, which is different from the response in babies?
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Which of the following is true regarding the location of NADH production?
Which of the following is true regarding the location of NADH production?
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Flashcards
Citric Acid Cycle
Citric Acid Cycle
A key metabolic pathway for energy extraction from food molecules, also known as Krebs cycle or TCA cycle.
Primary Role of Citric Acid Cycle
Primary Role of Citric Acid Cycle
To oxidize acetyl-CoA to carbon dioxide, generating energy carriers.
Energy Carriers
Energy Carriers
Molecules like NADH, FADH2, and GTP produced in the cycle, used to fuel ATP production.
Isocitrate Dehydrogenase
Isocitrate Dehydrogenase
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α-Ketoglutarate Dehydrogenase
α-Ketoglutarate Dehydrogenase
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Anaerobic Conditions
Anaerobic Conditions
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Control of the Cycle
Control of the Cycle
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Efficiency of Energy Use
Efficiency of Energy Use
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Proton Gradient
Proton Gradient
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Electrochemical Gradient
Electrochemical Gradient
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NADH and FADH2
NADH and FADH2
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F1-F0-ATP Synthase
F1-F0-ATP Synthase
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Oxidative Phosphorylation
Oxidative Phosphorylation
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Cyanide
Cyanide
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Carbon Monoxide
Carbon Monoxide
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ATP Yield from NADH and FADH2
ATP Yield from NADH and FADH2
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3-Succinyl-CoA synthetase
3-Succinyl-CoA synthetase
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Succinate dehydrogenase
Succinate dehydrogenase
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Citrate synthase
Citrate synthase
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Sources of NADH
Sources of NADH
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Function of O2 in ETC
Function of O2 in ETC
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Complex I of ETC
Complex I of ETC
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Coenzyme Q
Coenzyme Q
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Cytochromes
Cytochromes
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Uncouplers
Uncouplers
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Effects of Uncouplers
Effects of Uncouplers
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Brown adipose tissue
Brown adipose tissue
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2,4-DNP
2,4-DNP
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Bacterial Toxins
Bacterial Toxins
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NADH shuttle system
NADH shuttle system
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Streptococcus pneumoniae toxin
Streptococcus pneumoniae toxin
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Proton Motive Force
Proton Motive Force
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Study Notes
Citric Acid Cycle - Objectives
- The cycle's primary role is in cellular metabolism.
- This lecture introduces how the cycle functions as a key step in extracting energy from food molecules.
- Students will gain a comprehensive understanding of the significant steps, including the participating molecules and enzymes.
- The lecture will explore the reactions within the cycle, identifying how it regenerates a crucial intermediate for further fuel breakdown.
- Students will learn how the cycle produces energy carriers (NADH and FADH2), which fuel ATP production.
- The connection between the Citric Acid Cycle and the Electron Transport Chain, highlighting their roles in cellular respiration, will be explored.
Citric Acid Cycle (Krebs Cycle / TCA cycle)
- The citric acid cycle, also known as the Krebs cycle or the tricarboxylic acid cycle (TCA), occurs within the mitochondria.
- While oxygen isn't directly required in the cycle, it can't proceed anaerobically due to NADH and FADH2 accumulation if oxygen isn't present for the electron transport chain.
- Its primary function is the oxidation of acetyl-CoA to carbon dioxide.
- The energy released from this process is stored as NADH, FADH2, and GTP.
- Oxidation of glucose yields about 40% useable energy for ATP synthesis. The remaining 60% is lost as heat.
Key Points of TCA Cycle
- Isocitrate dehydrogenase is a major control enzyme. It's inhibited by NADH and ATP, activated by ADP.
- α-Ketoglutarate dehydrogenase is similar to pyruvate dehydrogenase. Requires thiamine, lipoic acid, CoA, FAD, and NAD. Deficiency in thiamine slows acetyl-CoA oxidation in the citric acid cycle.
Enzymes of the Citric Acid Cycle
- Citrate synthase: Condenses acetyl group and oxaloacetate to form citrate.
- Aconitase: Catalyzes citrate to isocitrate.
- Isocitrate dehydrogenase: Oxidizes isocitrate to α-ketoglutarate, releasing CO2 and producing NADH.
- α-Ketoglutarate dehydrogenase: Oxidizes α-ketoglutarate to succinyl-CoA, releasing CO2 and producing NADH.
- Succinyl-CoA synthetase: Converts succinyl-CoA to succinate, generating GTP (or ATP).
- Succinate dehydrogenase: Oxidizes succinate to fumarate, producing FADH2.
- Fumarase: Converts fumarate to malate.
- Malate dehydrogenase: Oxidizes malate to oxaloacetate, producing NADH.
Electron Transport Chain (ETC) Reactions
- NADH + O2 → NAD+ + H2O ΔG = -56 kcal/mol
- FADH2 + O2 → FAD + H2O ΔG = -42 kcal/mol
Proton Gradient
- The ETC generates electricity that powers proton pumps.
- Protons are moved from the matrix to the intermembrane space, creating a proton gradient (similar to pumping Na+ across a membrane).
- The three major complexes (I, III, and IV) translocate protons as electricity passes through them. The gradient is maintained across the mitochondrial inner membrane.
Oxidative Phosphorylation
- Proton flow into the mitochondria through the F0 component powers the F1 component (ATP synthase).
- Phosphorylates ADP using Pi to produce ATP.
- NADH oxidation typically yields 3 ATP molecules.
- FADH2 oxidation usually yields 2 ATP molecules.
Inhibitors of the Electron Transport Chain (ETC)
- Cyanide: Irreversibly binds to cytochrome a/a3, preventing electron transfer to oxygen, causing tissue hypoxia.
- Carbon monoxide: Binds to cytochrome a/a3, though less tightly than cyanide. Also binds to hemoglobin, displacing oxygen.
- Other inhibitors: Metformin, phenformin, rotenone, malonate, antimycin A, doxorubicin, oligomycin, GBNOXIN.
Uncouplers
- Uncouplers disrupt the proton gradient, leading to:
- Decreased ATP synthesis
- Increased oxygen consumption
- Increased NADH oxidation
- Important uncouplers include 2,4-dinitrophenol (2,4-DNP), aspirin, and other salicylates.
- Brown adipose tissue contains the protein UCP (thermogenin) enabling energy loss as heat to regulate temperature in newborns.
Bacterial Toxins as Uncouplers
- Some bacterial toxins (e.g., pneumolysin, staphylococcal α-toxin, listeriolysin O) create pores in membranes.
- This leads to proton leakage, decreasing ATP production efficiency — similar to uncouplers.
Fate of NADH
- Most NADH is generated inside mitochondria by the citric acid cycle.
- Glycolysis-derived NADH is in the cytosol.
- Mitochondrial inner membrane lacks direct NADH transport.
- Shuttle systems (e.g., glycerol-phosphate or malate-aspartate) carry reducing equivalents of cytosolic NADH into mitochondria.
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Description
Test your knowledge on the Citric Acid Cycle, a crucial metabolic pathway in cellular respiration. This quiz covers its function, regulation, and the enzymes involved in the process. Ideal for students studying biochemistry or related fields.