Start with zero energy and consider energy inputs/outputs.
Glycolysis requires energy investment:
Production of the reactive molecule glyceraldehyde-3-phosphate.
Energy release phase produces ATP and NADH.
Change in free energy (ΔG) decreases during glycolysis, indicating energy is being extracted.
Pyruvate enters mitochondria:
Undergoes a redox reaction, generating NADH.
Free energy of the molecule decreases as electrons are removed.
Pyruvate is converted to acetyl CoA via the enzyme pyruvate dehydrogenase.
In this process, energy is transferred to NADH.
Acetyl CoA enters the citric acid cycle:
Combines with oxaloacetate to form citrate.
Series of redox reactions occur, resulting in the loss of carbon dioxide and the reduction of NAD to NADH.
Key steps:
Conversion of alpha-ketoglutarate to succinyl CoA generates NADH.
Further steps lead to the production of ATP and GTP equivalents, NADH, and FADH₂.
Overall output of the citric acid cycle per glucose:
6 ATP equivalents (including GTP), 10 NADH, 2 FADH₂.
Glycolysis occurs in the cytosol.
Pyruvate is transported into the mitochondrial matrix:
Pyruvate oxidation and citric acid cycle occur in the matrix.
Importance of mitochondrial membranes:
Compartments (outer membrane, inner membrane space, inner membrane) crucial for energy extraction.
Mitochondria often referred to with metaphors:
Control panel or motherboard of the cell, processing information and energy.
Key areas:
Inner membrane contains proteins for electron transport and ATP synthesis.
Matrix holds electron carriers and reactions of the citric acid cycle.
NADH and FADH₂ hold high-energy electrons:
Approximate yield of 32 ATP molecules from 12 NADHs and FADH₂s.
Metaphor: NADH/FADH₂ = full-size candy bar, ATP = bite-sized energy chunks.
Composed of large protein complexes (Complex I, II, III, IV).
Electrons enter at Complex I (NADH) and Complex II (FADH₂).
Electrons passed along complexes reduce them while generating electrical current.
Oxygen serves as the final electron acceptor, forming water from excess protons.
Complex I: Oxidizes NADH, reduces itself, passes electrons to ubiquinone (Q).
Ubiquinone (Q): Mobile carrier in the membrane, moves electrons to Complex III.
Complex III and IV: Continuation of electron transport; final reception by oxygen.
Movement of electrons releases energy, reducing their energy potential on each transfer.
As electrons move through the system, their energy is released progressively:
High-energy on NADH, lower at each complex until stabilizing in water.
Affinity for electrons decreases through the cycle, culminating in stable water, which has low potential energy.
Protons are left behind during electron transfer.
If protons are not transferred with electrons, they accumulate in the matrix, influencing processes.
Understanding the change in free energy (ΔG) as electrons are transferred.
Recognizing how NADH gets oxidized back to NAD+ for reuse in metabolic pathways.
Considering the energetic landscape of electron transitions between complexes.
Electrons move through the chain due to a difference in electronegativity, facilitating energy release as they shift from high to low energy states.
NADH and FADH₂ are the main electron donors with NADH entering at Complex I and FADH₂ at Complex II.
NADH enters at Complex I:
Complex I oxidizes NADH, passing electrons to ubiquinone (Q) and releasing protons into the intermembrane space.
FADH₂ enters at Complex II:
Electrons from FADH₂ are transferred to Q without contributing protons.
Q transports electrons to Complex III:
Complex III passes electrons to cytochrome c while pumping additional protons.
Finally, Complex IV receives electrons:
Electrons are transferred to oxygen, reducing it to water and allowing protons to flow back to the matrix.
Protons are pumped from the mitochondrial matrix into the intermembrane space during electron transport.
This creates a proton-motive force, driving protons back into the matrix through ATP synthase.
F0 Subunit: Embedded in the membrane, forms a channel for protons to pass through.
F1 Subunit: Projects into the matrix and is responsible for ATP synthesis.
As protons flow back into the matrix through the F0 channel, it causes rotation in F0, transferring this energy to the F1 unit for ATP synthesis.
The proton gradient establishes potential energy, allowing the return of protons to the matrix through ATP synthase, converting potential energy into kinetic energy.
Protons move back through ATP synthase from the intermembrane space into the mitochondrial matrix, driving ATP production.
The flow of protons induces the rotation of the F0 subunit, facilitating conformational changes in the F1 subunit that synthesize ATP from ADP and inorganic phosphate (Pi).
This rotational mechanism is how ATP is generated in a process known as chemiosmosis.