Oxidative Phosphorylation Final Study

The proton motive force

is the electrochemical gradient generated by the movement of protons across the inner mitochondrial membrane during electron transport, driving ATP synthesis.

Structure of PMF

F_o domain: proton channel α-subunit and c-ring rotor

F₁ domain: α3​β3​hexer and rotating γ stalk

Binding Mechanism

1. Proton translocation through the a/c sub-channels causes the c-ring and attached γ subunit to rotate.

2. γ stalk rotates moving hexamer and forcing the 3β subunits into 3 conformations

• O(open): ATP release

• L(loose): ADP + Pi

• T(tight): ATP made

One full rotation makes 3 ATP

• 3 H+ passing through and one H+ consumed by translocate

Uncouplers

are compounds that disrupt the proton motive force, allowing protons to flow back into the mitochondrial matrix without generating ATP, resulting in heat production.

How do uncouplers affect heat production?

Uncouplers increase heat production by allowing protons to re-enter the mitochondrial matrix without passing through ATP synthase, thereby dissipating the proton motive force as heat instead of being converted into ATP.

How do uncouplers affect ATP production?

ATP yield drops to near zero

How do uncouplers affect Oxygen consumption?

They increase consumption bc the ETC must speed up due to the degredation of the PMF

Thermogenin

A mitochondrial uncoupling protein that facilitates the conversion of energy from the proton gradient into heat instead of ATP, playing a key role in non-shivering thermogenesis.

Mitochondrial Shuttles examples

include the malate-aspartate shuttle and the glycerol-3-phosphate shuttle, which transport reducing equivalents into the mitochondria for oxidative phosphorylation.

malate-aspartate shuttle

Predominant Tissues: Liver, Heart, Kidneys.

Yield: Delivers electrons directly to Complex I, yielding ∼2.5 ATP per cytosolic NADH

glycerol-3-phosphate shuttle

Predominant Tissues: Skeletal Muscle, Brain

Yield: Bypasses Complex I and enters at the level of CoQ, yielding ∼1.5 ATP per cytosolic NADH.

How do the mitochondrial shuttle systems entry points affect ATP yield

The entry points of mitochondrial shuttle systems significantly affect ATP yield by determining whether electrons are delivered to Complex I or at CoQ. This results in a yield of approximately 2.5 ATP per cytosolic NADH for the malate-aspartate shuttle and about 1.5 ATP for the glycerol-3-phosphate shuttle.