Lecture 7 — ETC & Oxidative Phosphorylation

What is oxidative phosphorylation?

ATP production driven by the proton gradient generated by the electron transport chain (ETC).

Where does the ETC occur?

At the inner mitochondrial membrane.

What is chemiosmosis?

Using a proton gradient across a membrane to drive ATP synthesis.

What is the difference between ETC and oxidative phosphorylation?

The ETC transfers electrons and builds a proton gradient; ATP synthase uses that gradient to produce ATP. Together they form oxidative phosphorylation.

Which ETC complexes pump protons?

Complexes I, III, and IV.

Which ETC complex does not pump protons?

Complex II.

What enters Complex I?

Electrons from NADH.

What is Complex I also called?

NADH–Q reductase.

How many protons does Complex I pump per two electrons?

4 H+ from matrix to intermembrane space.

Where does Complex I send electrons?

To coenzyme Q (CoQ).

What is CoQ also called?

Ubiquinone, CoQ10, or Q10.

What is the reduced form of CoQ?

Ubiquinol (QH2).

What is the reduction reaction for CoQ?

Q + 2 e− + 2 H+ → QH2.

What is Complex II associated with in the TCA cycle?

Succinate dehydrogenase.

What does Complex II do?

Transfers electrons from FADH2 to CoQ without pumping protons.

Why does FADH2 generate less ATP than NADH?

Its electrons enter at Complex II and bypass proton-pumping Complex I.

What is Complex III called?

Cytochrome c reductase.

What does Complex III do?

Transfers electrons from QH2 to cytochrome c and contributes 4 H+ to the gradient per two electrons.

What does cytochrome c carry?

Electrons from Complex III to Complex IV.

What is Complex IV called?

Cytochrome c oxidase.

What is the final electron acceptor of the ETC?

Oxygen (O2).

What happens to oxygen at Complex IV?

It accepts electrons and H+ to form water.

How many protons does Complex IV pump per two electrons?

2 H+.

What is the electron path from NADH?

NADH → Complex I → CoQ → Complex III → cytochrome c → Complex IV → O2.

What is the electron path from FADH2?

FADH2 → Complex II → CoQ → Complex III → cytochrome c → Complex IV → O2.

What is Complex V?

ATP synthase.

Which direction do protons flow through ATP synthase?

From the intermembrane space back into the matrix.

How does ATP synthase make ATP?

Proton flow drives rotation and conformational changes that catalyze ADP + Pi → ATP.

What is the F0 region of ATP synthase?

The membrane-embedded proton-conducting and rotor region.

What is the F1 region of ATP synthase?

The matrix-facing catalytic headpiece with three alpha-beta pairs.

What do the c subunits do?

Form the rotating proton-driven rotor.

What does the gamma subunit do?

Acts as a rotating shaft connecting the F0 rotor to the F1 catalytic head.

What happens with a 120-degree gamma rotation?

The gamma shaft interacts with a new alpha-beta catalytic pair, changing its ATP-binding or release state.

Where is ATP released by ATP synthase?

Into the mitochondrial matrix.

Why can't cytosolic NADH simply enter the ETC?

NADH itself is not transported across the inner mitochondrial membrane; its electrons are shuttled.

What are the two major cytosolic NADH shuttles?

Glycerol 3-phosphate shuttle and malate-aspartate shuttle.

Which shuttle is faster but less efficient?

Glycerol 3-phosphate shuttle.

How much ATP does the glycerol 3-phosphate shuttle yield per cytosolic NADH?

About 1.5 ATP.

Which shuttle is slower but more efficient?

Malate-aspartate shuttle.

How much ATP does the malate-aspartate shuttle yield per cytosolic NADH?

About 2.5 ATP.

How many protons are pumped per NADH electron pair across Complexes I III IV?

10 H+ total: 4 + 4 + 2.

How many protons are pumped per FADH2 electron pair across Complexes II III IV?

6 H+ total: 0 + 4 + 2.

What reactive oxygen species are discussed as ETC byproducts?

Superoxide and hydrogen peroxide.

What is the consequence of excessive reactive oxygen species?

Oxidative damage associated with inflammation and chronic disease.

What does rotenone inhibit?

Electron transfer from Complex I to CoQ.

What do Amytal and Demerol inhibit according to the lecture?

Electron transfer from Complex I to CoQ.

What do cyanide and carbon monoxide disrupt?

Terminal electron transfer involving cytochrome oxidase, preventing normal oxygen reduction.

What does metformin do to Complex I according to the lecture?

Decreases Complex I activity, NADH oxidation, proton pumping, oxygen consumption, and ATP synthesis.

What does oligomycin inhibit?

ATP synthase, reducing or preventing proton-driven ATP formation.

What happens to ATP synthesis if the proton gradient collapses?

ATP synthase loses its driving force and ATP synthesis falls.

Why is the inner mitochondrial membrane important?

It separates the matrix from the intermembrane space so an electrochemical proton gradient can form.

What does the TCA cycle supply to the ETC?

Reduced electron carriers NADH and FADH2.

What is the main take-home message of this lecture?

Electron transfer builds a proton gradient and ATP synthase converts its energy into ATP.