Biochemistry: Pyruvate Oxidation and TCA Cycle

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Questions and Answers

What is the function of the pyruvate dehydrogenase complex (PDHc) in cellular metabolism?

To synthesize GTP from acetic acid

To convert acetyl-CoA to pyruvate

To generate NAD+ from NADH

To oxidize pyruvate to acetyl-CoA and CO2 (correct)

Which components are vital for the regulation of the TCA cycle?

NADH levels only

ATP levels and enzyme concentration

Acetyl-CoA concentration exclusively

Substrate availability and allosteric effectors (correct)

How does the respiratory chain utilize reducing equivalents during cellular respiration?

By storing them as fat

Through direct conversion into ATP without a proton gradient

By converting them back into glucose

By oxidizing NADH and FADH2 and acting as a proton pump (correct)

Which enzyme catalyzes a reaction in the TCA cycle that produces reducing equivalents?

Malate dehydrogenase Signup and view all the answers

What role do mobile electron carriers such as coenzyme Q and cytochrome c play in the respiratory chain?

They transfer electrons between the protein complexes Signup and view all the answers

What is a potential consequence of a deficiency in the pyruvate dehydrogenase complex?

Accumulation of lactic acid due to anaerobic metabolism Signup and view all the answers

Which theory explains the process of ATP synthesis in oxidative phosphorylation?

The chemiosmotic theory Signup and view all the answers

Which factor does not influence the activity of the TCA cycle enzymes?

Dietary intake of carbohydrates Signup and view all the answers

What is the primary action of inhibitors on the respiratory chain?

They inhibit the process of oxidative phosphorylation. Signup and view all the answers

Which complex does cyanide inhibit in the electron transport chain?

Complex IV Signup and view all the answers

How does the binding affinity of carbon monoxide compare to that of oxygen with hemoglobin?

Carbon monoxide binds more effectively than oxygen. Signup and view all the answers

What effect do barbiturates have on the respiratory chain?

They act as inhibitors of respiration. Signup and view all the answers

In which compartment of the cell does oxidative phosphorylation primarily occur?

Mitochondria Signup and view all the answers

Which statement accurately describes the function of the mitochondrial respiratory chain?

It facilitates the transfer of electrons to produce ATP. Signup and view all the answers

What is the main consequence of inhibiting Complex IV?

Decreased oxygen utilization. Signup and view all the answers

What role do inhibitors of the respiratory chain play in cellular metabolism?

They decrease ATP generation. Signup and view all the answers

What is the main purpose of the citric acid cycle?

To harvest high-energy electrons from carbon fuels Signup and view all the answers

Which intermediate is formed from acetyl-CoA during the citric acid cycle?

Citrate Signup and view all the answers

What is the significance of the oxidation of malate to oxaloacetate in the cycle?

It is a reversible reaction Signup and view all the answers

Which product is formed during the oxidative decarboxylation of α-ketoglutarate?

Succinyl-CoA Signup and view all the answers

What is the Gibbs free energy change (ΔG°ˊ) for the formation of citrate from oxaloacetate?

−32.2 kJ/mol Signup and view all the answers

Which vitamin is NOT mentioned as a cofactor in the oxidative decarboxylation process?

Pyridoxine Signup and view all the answers

Why is the reaction from malate to oxaloacetate driven forward in intact cells?

Oxaloacetate is continually removed by another reaction Signup and view all the answers

Which of the following is NOT an intermediate of the TCA cycle?

Acetyl-CoA Signup and view all the answers

What type of reaction is the conversion of citrate to isocitrate?

Rearrangement Signup and view all the answers

What is the main role of anaplerotic reactions in the TCA cycle?

To replenish intermediates that are depleted Signup and view all the answers

Which statement correctly describes the electron transport chain?

It reduces oxygen to form water Signup and view all the answers

How many protons are required to drive the synthesis of one ATP according to the chemiosmotic hypothesis?

4 protons Signup and view all the answers

What is the function of cytochrome c in the electron transport chain?

Carries one electron between complexes Signup and view all the answers

Why does FADH2 produce less ATP compared to NADH in the electron transport chain?

It enters the chain at a later stage Signup and view all the answers

What is the primary control mechanism for the activity of the electron transport chain?

Concentration of ADP and ATP Signup and view all the answers

Which compound serves as a mobile electron carrier in the electron transport chain?

Ubiquinone Signup and view all the answers

Which process involves the coupling of electron transport to ATP synthesis?

Chemiosmosis Signup and view all the answers

What is produced as a byproduct of glucose oxidation in cellular respiration?

Carbon dioxide and water Signup and view all the answers

What type of metabolic pathway does the TCA cycle represent?

Amphibolic Signup and view all the answers

Which molecule is primarily responsible for carrying reducing equivalents in the respiratory chain?

NADH Signup and view all the answers

What happens to electron carriers in the electron transport chain after they donate their electrons?

They are recycled back to their original state Signup and view all the answers

What role does ATP synthase play in cellular respiration?

It synthesizes ATP using a proton gradient Signup and view all the answers

Where does oxidative phosphorylation primarily occur within the cell?

Inner mitochondrial membrane Signup and view all the answers

What is the final electron acceptor in the electron transport chain?

Oxygen Signup and view all the answers

What is the role of the glycerophosphate shuttle in cellular metabolism?

It transfers reducing equivalents from cytosol to the mitochondrial matrix. Signup and view all the answers

What is the primary effect of 2,4-DNP in the body?

It disrupts the proton gradient across the mitochondrial membrane. Signup and view all the answers

Which shuttle utilizes the cytosolic and mitochondrial isoforms of malate dehydrogenase?

Malate shuttle Signup and view all the answers

Superoxide dismutase plays a crucial role in the detoxification of which type of reactive species?

Superoxide Signup and view all the answers

Which metabolic pathway is primarily affected by the inhibition of ATP synthase?

Oxidative phosphorylation Signup and view all the answers

What is a significant consequence of generating heat in brown adipose tissue?

Thermogenesis without ATP generation Signup and view all the answers

Which enzyme is responsible for transaminating glutamate to form aspartate?

Aspartate aminotransferase Signup and view all the answers

How many molecules of ATP are produced when glucose is fully oxidized?

32 ATP per molecule of glucose Signup and view all the answers

The malate shuttle is primarily utilized for transporting which type of equivalents?

Reducing equivalents Signup and view all the answers

What mechanism allows 2,4-DNP to promote weight loss?

By uncoupling oxidative phosphorylation Signup and view all the answers

Study Notes

Pyruvate Oxidation

Pyruvate is oxidized to acetyl-CoA and CO2 inside the mitochondria
Pyruvate dehydrogenase complex (PDHc) is responsible for this process
PDHc contains three enzymes: E1, E2, and E3
Four water-soluble vitamins are crucial for pyruvate oxidation: thiamin, riboflavin, niacin, and pantothenic acid
Lipoate is also involved in the process
PDH is regulated by allosteric effectors and covalent modification
Deficiencies or dysregulation of PDHc can have clinical significance

TCA Cycle

Acetyl-CoA is oxidized in the TCA cycle to generate CO2, reducing equivalents (NADH & FADH2), and GTP
The cycle consists of eight enzymatic steps:
- Citrate synthase catalyzes the formation of citrate from oxaloacetate and acetyl-CoA
- Aconitase converts citrate to isocitrate
- Isocitrate dehydrogenase oxidizes isocitrate while forming NADH and CO2
- Alpha-ketoglutarate dehydrogenase complex (α-KGDH) is similar to PDHc and catalyzes the formation of succinyl-CoA, NADH, and CO2
- Succinyl-CoA synthetase converts succinyl-CoA to succinate, producing GTP
- Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate, producing FADH2
- Fumarase converts fumarate to malate
- Malate dehydrogenase produces oxaloacetate from malate, generating NADH
The cycle is highly exergonic and thermodynamically favorable
The TCA cycle is regulated by substrate availability and allosteric effectors
Dysregulation of TCA cycle enzymes, such as SDH, can have clinical significance

Oxidative Phosphorylation and ETC

Four protein complexes (I, II, III, IV) and mobile electron carriers (Q & cytochrome c) are involved in the ETC
The respiratory chain oxidizes reducing equivalents (NADH and FADH2), acting as a proton pump
The chemiosmotic theory explains ATP synthesis through proton gradient generation across the inner mitochondrial membrane
Inhibitors can block specific steps in the ETC or oxidative phosphorylation, including rotenone, cyanide, antimycin A, and oligomycin
The glycerol phosphate shuttle and malate-aspartate shuttle transfer reducing equivalents from the cytoplasm to the mitochondria
Superoxide dismutase protects the ETC from oxidative damage

Electron Transport Chain

The ETC (respiratory chain) involves the sequential transfer of electrons from NADH or FADH2 to oxygen
Complex I (NADH-Q oxidoreductase) receives electrons from NADH and transfers them to Q
Complex II (succinate-Q reductase) receives electrons from FADH2 and transfers them to Q
Complex III (Q-cytochrome c oxidoreductase) accepts electrons from Q and passes them to cytochrome c
Complex IV (cytochrome c oxidase) receives electrons from cytochrome c and transfers them to oxygen, producing water

Oxidative Phosphorylation

The proton gradient generated by the ETC drives ATP synthesis
ATP synthase uses the gradient to phosphorylate ADP to ATP
The ETC and oxidative phosphorylation generate ATP efficiently from glucose oxidation
FADH2 produces less ATP than NADH due to its entry point in the ETC

Amphibolic Nature of TCA

The TCA cycle is amphibolic, meaning it plays roles in both energy production and biosynthetic pathways, including gluconeogenesis, amino acid synthesis, and fatty acid synthesis
Anaplerotic reactions replenish TCA cycle intermediates, ensuring its continuous operation### ATP Synthase
Inhibits oxidation and phosphorylation by blocking proton flow through ATP synthase.

Glycerol 3-phosphate Shuttle

Transfers reducing equivalents from cytosol to mitochondrial matrix
Utilizes cytosolic and mitochondrial isoforms of Glycerol-3-P DH.

Malate Shuttle

Transfers reducing equivalents from cytosol to mitochondrial matrix.
Utilizes cytosolic and mitochondrial isoforms of Malate DH.
The same enzyme but different locations.

Glutamate-Oxaloacetate Transaminase

Also known as Aspartate aminotransferase.
Transports reducing equivalents from cytosol to mitochondrial matrix.

Brown Adipose Tissue

Rich in mitochondria to generate heat (thermogenesis).
2,4-Dinitrophenol (2,4-DNP) increases uncoupling in brown adipose tissue.
Increases mitochondrial permeability and reduces ATP synthesis, leading to increased heat production.

Superoxide Dismutase

Neutralizes superoxide radicals (O2-)
Superoxide radicals are reactive oxygen species.

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Description

Explore the intricacies of pyruvate oxidation and the TCA cycle in this quiz. Focus on the key processes, enzymes involved, and the importance of specific vitamins in energy metabolism. Test your understanding of metabolic pathways and their regulation.