Reading-TCA, ETC & Oxidative Phosphorylation

6,9

What regulates the activity of the PDH complex

PDH kinase which phosphorylates and inactivates the complex

How does the [ATP]/[ADP] ratio affect isocitrate dehydrogenase activity in the TCA cycle

A high [ATP]/[ADP] ratio inhibits the enzyme

How does [NADH] affect isocitrate dehydrogenase and α-ketoglutarate dehydrogenase

It inhibits both enzymes as a product feedback regulator

How does succinyl CoA regulate α-ketoglutarate dehydrogenase

It inhibits the enzyme through product feedback

What is the effect of Ca²⁺ on PDH complex and α-ketoglutarate dehydrogenase

It activates both enzymes to increase TCA cycle flux

Why does the liver produce citrate in the well-fed state

To lower blood glucose by diverting excess acetyl-CoA into citrate for anabolic processes

How does citrate production help prevent hyperglycemia

By providing a sink for acetyl-CoA that promotes fatty acid and cholesterol synthesis instead of further glucose oxidation

What are the two competing fates of citrate in the cell

Oxidation in the TCA cycle or export to the cytosol for biosynthesis

What happens to citrate in the cytosol

It is used for fatty acid and cholesterol synthesis

How does elevated cytosolic citrate regulate glycolysis

It allosterically inhibits PFK-1 to slow down glycolysis

What links the TCA cycle and the Electron Transport Chain

The TCA cycle produces NADH and FADH2 which donate electrons to the ETC

What does the Electron Transport Chain establish across the inner mitochondrial membrane

A proton (H⁺) concentration gradient creating a chemical potential

What reaction does ATP synthase catalyze in oxidative phosphorylation

The formation of ATP from ADP and inorganic phosphate (Pi)

At which complex in the ETC is oxygen reduced to water

Complex IV

Which molecules transfer electrons within the ETC

Coenzyme Q10 (CoQ10) and cytochromes

Where are protons pumped during electron transport

Into the intermembrane space of the mitochondrion

What is the principal product of mitochondrial metabolism (TCA + ETC + OxPhos)

Thermal energy (heat)

Why must the body produce and reject heat

To maintain a low entropy

How does the entropy of the external environment change during mitochondrial metabolism

It increases as heat is released to the environment

What is the proton motive force

The electrochemical gradient of H⁺ across the inner mitochondrial membrane that drives ATP synthesis

What does the P/O ratio represent

The number of ATP molecules synthesized per atom of oxygen reduced

How many ATP are produced from one NADH via oxidative phosphorylation

Approximately 2.5 ATP

How many ATP are produced from one FADH₂ via oxidative phosphorylation

Approximately 1.5 ATP

What is the role of uncoupling proteins like UCP1

They dissipate the proton gradient as heat rather than using it to produce ATP

What is the effect of cyanide or carbon monoxide on the ETC

They inhibit Complex IV

What happens when oligomycin inhibits ATP synthase

Proton flow is blocked

What occurs to the ETC activity when ATP synthesis is blocked

Electron transport slows or stops due to the buildup of the proton gradient

How is reactive oxygen species (ROS) formation linked to the ETC

Leakage of electrons from complexes I and III can reduce O₂ to form superoxide

Why does FADH₂ contribute fewer protons to the gradient than NADH

FADH₂ donates electrons at Complex II which does not pump protons across the inner mitochondrial membrane

Why does electron flow occur in a specific direction through the ETC

Each successive complex has a higher standard reduction potential

What is the function of cytochrome c in the ETC

It is a mobile electron carrier that transfers electrons from Complex III to Complex IV

Why is oxygen essential to mitochondrial respiration

It acts as the final electron acceptor forming water at Complex IV

How is ADP availability a regulator of oxidative phosphorylation

Low [ADP] limits ATP synthase activity

Why does mitochondrial membrane integrity matter for ATP synthesis

The proton gradient must be maintained across an intact inner mitochondrial membrane for ATP synthase to function

How does the glycerol phosphate shuttle influence ATP yield

It transfers cytosolic NADH electrons to FAD in mitochondria

How is thermogenesis achieved in brown adipose tissue

UCP1 (thermogenin) uncouples oxidative phosphorylation by dissipating the proton gradient as heat

What role does cardiolipin play in the ETC

It stabilizes the structure of ETC complexes in the inner mitochondrial membrane

How is mitochondrial respiration linked to apoptosis

Cytochrome c release from mitochondria into the cytosol activates caspases that drive programmed cell death

How does the proton motive force drive ATP synthesis

The electrochemical gradient (Δp) of protons across the inner mitochondrial membrane powers ATP synthase to convert ADP and Pi into ATP

Why does ATP synthase require rotational catalysis to function

Conformational changes in the F₁ subunit induced by rotor rotation allow sequential binding of ADP + Pi

What happens to ETC function during hypoxia or ischemia

Lack of oxygen halts electron flow at Complex IV

How do mutations in ETC proteins contribute to disease

Mutations impair electron flow or proton pumping

How does mitochondrial uncoupling affect metabolic rate

It increases substrate oxidation and oxygen consumption without producing ATP

Why is Coenzyme Q (ubiquinone) considered a redox-active lipid

It can reversibly accept and donate electrons and protons

What is the significance of "respiratory control" in mitochondria

Electron flow and oxygen consumption are tightly coupled to ADP availability

How do reactive oxygen species (ROS) arise from the ETC

Electrons can leak at Complexes I and III

Why is Complex II the only ETC complex not involved in proton pumping

Its structure and position in the inner membrane are suited for electron entry from FADH₂ but not for translocating protons

How does NADH from cytosolic glycolysis enter mitochondrial respiration

Through the malate-aspartate or glycerol-3-phosphate shuttle systems which transfer reducing equivalents into the matrix

How does Complex IV of the ETC contribute to maintaining the proton gradient

It reduces O₂ to H₂O while simultaneously pumping protons into the intermembrane space

Why does the presence of an uncoupling protein in brown adipose tissue benefit newborns

It allows proton re-entry without ATP synthesis

How is the ETC affected by cyanide or carbon monoxide poisoning

These agents bind to Complex IV

How does FADH₂ oxidation at Complex II compare to NADH oxidation at Complex I in terms of ATP yield

FADH₂ enters downstream of Complex I and contributes fewer protons to the gradient

Why is the inner mitochondrial membrane impermeable to protons

It ensures the electrochemical gradient is maintained for ATP synthase function

How does ischemia-reperfusion injury involve the ETC

Sudden reoxygenation causes rapid electron flow and ROS generation

Why is cardiolipin essential for optimal ETC function

This unique phospholipid stabilizes ETC complexes and supports supercomplex formation in the inner membrane

How does mitochondrial calcium uptake influence ETC activity

Ca²⁺ activates dehydrogenases in the TCA cycle

What role does Complex III play in the Q cycle

It facilitates electron transfer from ubiquinol to cytochrome c and contributes to proton pumping via a bifurcated pathway

How does mitochondrial membrane potential influence metabolite transport

A strong potential drives electrogenic transport systems for ATP/ADP exchange and phosphate import

What is the primary thermodynamic driving force of ATP synthesis during oxidative phosphorylation

The proton-motive force generated by the electrochemical H⁺ gradient across the inner mitochondrial membrane

How does ATP synthase convert mechanical energy into chemical energy

Proton flow through the F₀ subunit causes conformational rotation in the F₁ subunit to catalyze ATP formation

What happens when ADP levels are low in the mitochondrion

The rate of electron flow through the ETC slows due to backpressure from the proton gradient

Why is the inner mitochondrial membrane folded into cristae

To increase surface area and enhance capacity for oxidative phosphorylation

How does the adenine nucleotide translocase support oxidative phosphorylation

It exchanges ATP out and ADP in across the inner membrane to fuel continuous ATP production

What would happen if the mitochondrial membrane became permeable to protons

The proton gradient would collapse

How is oxidative phosphorylation regulated by cellular energy demand

High [ATP]/[ADP] ratios inhibit the ETC

How do reactive oxygen species (ROS) arise from the ETC

Electrons leak from Complex I or III to oxygen

How do cells mitigate the oxidative stress caused by ETC-generated ROS

Enzymes like superoxide dismutase

Why is the ETC considered the major site of oxygen consumption in aerobic cells

Because Complex IV requires oxygen as the terminal electron acceptor to form water