TCA Cycle & Oxidative Phosphorylation Flashcards
Where does the link reaction take place?
Mitochondria
What is the link reaction?
Pyruvate + CoA + NAD+ –> acetyl CoA + carbon dioxide + NADH + H+
What kind of reaction is the link reaction?
Oxidative decarboxylation
What is the order of compounds in the TCA cycle?
Oxaloacetate | (+ acetyl CoA) Citrate | Isocitrate | a-ketoglutarate | Succinyl CoA | Succinate | Fumarate | Malate
How many carbons does oxaloacetate have?
4
How many carbons does citrate have?
6
How many carbons does acetyl CoA have?
2
How many carbons does pyruvate have?
3
How many carbons does isocitrate have?
6
How many carbons does a-ketoglutarate have?
5
How many carbons does succinyl CoA have?
4
How many carbons does succinate have?
4
How many carbons does fumarate have?
4
How many carbons does malate have?
4
At which stages is carbon dioxide released in the TCA cycle?
- Isocitrate to a-ketoglutarate
4. a-ketoglutarate to succinyl CoA
What is the structure of oxalic acid?
HOOC–COOH
What is the structure of malonic acid?
HOOC–CH2–COOH
What is the structure of succinic acid?
HOOC–CH2–CH2–COOH
What is the structure of glutaric acid?
HOOC–CH2–CH2–CH2–COOH
What enzyme catalyses the formation of oxaloacetate to citrate?
Citrate synthase
What enzyme catalyses the formation of citrate to isocitrate?
Aconitase
What enzyme catalyses the formation of isocitrate to a-ketoglutarate?
Isocitrate dehydrogenase
What enzyme catalyses the formation of a-ketoglutarate to succinyl CoA?
a-ketoglutarate dehydrogenase
What enzyme catalyses the formation of succinyl CoA to succinate?
Succinyl CoA synthase/synthetase
What enzyme catalyses the formation of succinate to fumarate?
Succinate dehydrogenase
What enzyme catalyses the formation of fumarate to malate?
Fumarase
What enzyme catalyses the formation of malate to oxaloacetate?
Malate dehydrogenase
In which reactions is NAD+ reduced?
- Isocitrate to a-ketoglutarate
- a-ketoglutarate to succinyl CoA
- Malate to oxaloacetate
In what reaction is FAD reduced (TCA)?
- Succinate to fumarate
In what reaction is GTP produced (TCA)?
- Succinyl CoA to succinate
What is oxidative phosphorylation?
Reoxidation of NADH and FADH2 via the electron transport chain
Synthesis of ATP directly from ADP and Pi
How many reduced NAD+ are formed in one TCA cycle?
3
How many reduced FAD are formed in one TCA cycle?
1
How many GTP are formed in one TCA cycle?
1
How many ATP are formed per reoxidised NADH?
2.5
How many ATP are formed per reoxidised FADH2?
1.5
Which enzymes catalyse irreversible stages of the TCA cycle?
- Citrate synthase
- Isocitrate dehydrogenase
- a-ketoglutarate dehydrogenase
What is another function of oxaloacetate?
Transamination to aspartate/aspartic acid
To form other amino acids, purines and pyrimidines
What is another function of a-ketoglutarate?
Transamination to glutamate/glutamic acid
To form other amino acids and purines
What is another function of succinyl CoA?
Used to form haem
How is pyruvate converted back to glucose?
Pyruvate to oxaloacetate by pyruvate carboxylase
Oxaloacetate to phosphoenol pyruvate by PEP carboxylase
What is another name for the electron transport chain?
Cytochrome chain
Where is the electron transport chain found?
Embedded in inner mitochondrial membrane
What components of the electron transport chain accept a pair of hydrogen atoms?
Flavin cofactors
Coenzyme Q
What components of the electron transport chain accept an electron?
Iron-sulphur proteins
Cytochrome proteins
Why can iron-sulphur proteins carry electrons?
Fe ion has variable oxidation states (Fe2+ Fe3+)
Why can cytochrome proteins carry electrons?
Contain a haem ring with an Fe ion which has variable oxidation states
What is an oxido-reduction (redox) potential?
Describes the ability of a carrier to donate its electron to another carrier
In which direction do electrons flow between carriers?
More negative to more positive redox potentials
Highest to lowest energy carriers
What is the highest energy electron carrier?
NAD+
What is the lowest energy electron carrier?
Oxygen
What is the order of the components of the electron transport chain for NADH?
Complex I (NADH dehydrogenase complex)
CoQ (ubiquinone)
Complex III (cytochrome C reductase complex)
Cytochrome C
Complex IV (cytochrome C oxidase complex)
What another name for complex I?
NADH dehydrogenase complex
What is another name for complex III?
Cytochrome C reductase complex
What is another name for complex IV?
Cytochrome C oxidase complex
Where is CoQ found?
Embedded in inner mitochondrial membrane (long hydrophobic R group)
What is another name for CoQ?
Ubiquinone
Which components of the electron transport chain are mobile?
CoQ/ubiquinone
Cytochrome C
What electron carriers are present in complex I?
Flavin mononucleotide
Iron-sulphur protein
What electron carriers are present in complex III?
Cyt b
Iron-sulphur protein
Cyt c1
What electron carriers are present in complex IV?
Cyt a
Cyt a3
What happens at the complexes in the electron transport chain?
Electrons are passed step-wise between carriers
Energy released by transfer is used to actively pump protons from the mitochondrial matrix to the intermembrane space (not in complex II)
Oxygen reduced to water at complex IV
What is the pH in the intermembrane space?
7.2
What is the pH in the matrix?
7.9
How is the pH gradient created across the inner mitochondrial membrane?
Active transport of protons out of the matrix by complexes in the electron transport chain
What causes the voltage gradient across the inner mitochondrial membrane?
Charge difference/moving ions out of the matrix
How do you calculate the electrochemical gradient across the inner mitochondrial membrane?
ΔV + ΔpH
What is another term for electrochemical gradient?
Proton-motive force
What energy transduction occurs when protons move through ATP-synthase?
Kinetic to mechanical (rotation/conformational change)
Why is the electron transport chain for FADH2 different to that of NADH?
FADH2’s reducing ability/power is too weak to pass electrons to complex I so passes electrons to complex II instead
What is the order of the components of the electron transport chain for FADH2?
Complex II
CoQ
Complex III (cytochrome C reductase complex)
Cytochrome C
Complex IV (cytochrome C oxidase complex)
Which complex does not have the ability to move protons across the inner mitochondrial membrane?
Complex II
Why is less ATP formed in the reoxidation of FADH2?
Complex II cannot pump protons across membrane
So smaller pH gradient
So smaller electrochemical gradient
So less protons moving through ATP-synthase
What increases oxygen uptake for oxidative phosphorylation?
Increased ADP concentration
What decreases oxygen uptake for oxidative phosphorylation?
Increased ATP concentration
What can inhibit oxidative phosphorylation?
Carbon dioxide and carbon monoxide inhibit the cytochrome proteins by binding to haem group
Rotenone inhibits CoQ
What does an uncoupler do?
Acts as a ‘back-door’ alternative to ATP-synthase for protons to move back into the matrix
What is the effect of an uncoupler?
Energy from movement of protons across membrane not used to generate ATP but instead lost as heat
Give an example of a good/beneficial uncoupler
Thermogenin protein in brown adipose tissue helps keep babies warm
Give an example of a bad uncoupler
Dinitrophenol/DNP in weight loss pills
How much ATP is generated from the complete oxidation of one glucose molecule?
30 or 32ATP
Why can the amount of ATP generated by the complete oxidation of a glucose molecule vary?
NADH generated in glycolysis can be moved into mitochondria for oxidative phosphorylation by two different pathways