Oxidative Phosphorylation and Electron Transport Chain

The citric acid cycle's importance lies in its ability to produce energy from fats, proteins, and nucleic acids.

The primary focus is on generating energy through efficient processes.
Mitochondria are present in almost every cell in the body, except red blood cells, producing ATP.
ATP is required for various cellular functions, including signaling (covalent and allosteric modifications), transport, and muscle function.
ATP is also involved in pain reception.

The study of oxidative phosphorylation is essential for understanding energy metabolism, cellular homeostasis, and disease research.
The overview involves electron collection and movement from one complex to another.
Electron movement generates energy to pump protons out of the mitochondrial matrix, creating a gradient.
The proton gradient's energy is used by complex five (a mechanical machine) to generate ATP.
Eukaryotic and most prokaryotic cells contain these proteins and structures.

Understanding the scene of action (mitochondria) and energy changes in biological oxidations.
Review of basic chemistry concepts, especially oxidation-reduction reactions.

Amino acids, pyruvate, and fatty acids feed into Acetyl CoA, which enters the citric acid cycle.
The electron transport chain is the main focus.
Energy is produced at every step, releasing energy in reduced forms like NADH, FADH2, or directly as ATP.

The mitochondria's structure varies depending on the cell type (e.g., more cristae in muscle cells).
Shapes and sizes of mitochondria are variable.
The inner membrane is packed with proteins (70-76%), including electron transport chain complexes.
Outer membrane, inner membrane, matrix, intermembrane space, and cristae are key structural components.

Electrons are fed to complex one via NADH.
Electrons move to complex two via FADH2 (succinate dehydrogenase).
Coenzyme Q carries electrons between complexes; it is hydrophobic and embedded in the membrane.
Electron movement through complexes pumps out protons.
Cytochrome c, located outside the membrane, carries electrons to complex four.
Complex four pumps out protons and converts oxygen to H2O.
The proton gradient drives ATP production.

Reduction is gaining electrons; oxidation is losing electrons (OIL RIG).
A general form involves a reducing agent (A) losing electrons and another substance (B) gaining them.
Faraday's constant is used to calculate the standard free energy change ( $\Delta G$ ).
$\Delta G = -nF\Delta E_0$ where:
- $n$ is the number of electrons transferred.
- $F$ is Faraday's constant.
- $\Delta E_0$ is the difference in standard reduction potential.
Reaction spontaneity depends on electron availability.

Glycolysis and the citric acid cycle perform half the reaction, releasing CO2.
Glucose is oxidized with water to produce $6CO_2$ , 24 hydrogens, and 24 electrons.
The other half occurs in the mitochondria, where $6O<em>2$ combines with 24 hydrogens and 24 electrons to produce $12H</em>2O$ .
The electron transport chain and oxidative phosphorylation are involved.
Each hydrogen in a reduced cofactor equals two electrons.

Two NADH in glycolysis yield four electrons.
Pyruvate dehydrogenase complex produces four electrons.
The citric acid cycle generates 12 electrons from 6 NADH and 2 electrons from 1 FADH2.
Most electrons are generated in the citric acid cycle.
NADH and FADH2 want to lose electrons, driving oxidative phosphorylation.

Electrons flow from hydrogen (negative charge) to copper (positive charge) in a galvanic cell.
In biochemistry, FADH2 and NADH replace hydrogen gas.
Hydrogen gains an electron with a standard electrode potential of -0.421.
Biochemical standard reduction potential is measured at pH 7 (E0).
More reducing power is at the top, and more oxidizing power is at the bottom.
Oxygen + 2H + 2 electrons -> H2O (highly oxidative reaction).

Electrons move from NADH to oxygen through complexes, with incremental changes in electrode potential.
NADH has a -0.315 potential, while oxygen has a +0.815 potential.
Electron movement generates a current that pumps protons out.
Energy from electron movement pumps protons out at almost every step.

Complex one, two, three, four, and five are involved.
Complex one receives NADH, and complex two (succinate dehydrogenase) receives FADH2.
Complex two does not pump protons.
Complexes one, three, and four pump protons using coenzyme Q to move electrons.
Oxygen acts as the final electron acceptor, producing H2O.

Proteins are transferred using four main electron carriers:
- Flavoproteins (FMN or FAD)
- Iron-sulfur proteins (FeS)
- Coenzyme Q (ubiquinone)
- Cytochromes (containing hemes)
Metals facilitate oxidation-reduction reactions.
Electrons are kept at a distance from metal centers to prevent reactions and maintain usability.
Coenzyme Q is lipophilic and can transfer two electrons in one-electron steps.

Complex one (NADH-coenzyme Q reductase) pumps four protons.
It transports two electrons from NADH to CoQ, causing a conformational change.
Complex two (succinate-coenzyme Q reductase or succinate dehydrogenase) transfers two electrons from succinate through FAD and iron-sulfur clusters to CoQ but does not pump protons.
Coenzyme Q collects electrons from complex one, complex two, and other flavoproteins.
Complex three (coenzyme Q-cytochrome c oxidoreductase) transfers electrons from CoQH2 to cytochrome c, pumping four protons.
Complex four catalyzes the transfer of electrons from reduced cytochrome c to oxygen, pumping four protons and oxidizing oxygen to H2O.

Rotenone and amytal inhibit complex one.
Antimycin A and cyanide inhibit complex four.
These inhibitors disrupt the electron transport chain by preventing electron acceptance, halting ATP production.

Electron flow is from most negative to most positive.
The mitochondrial electron transport chain consists of four membrane-embedded proteins, two mobile electron carriers (coenzyme Q and cytochrome c), and three main chemical reactions:
- NADH to NAD+
- Succinate to fumarate
- Oxygen to water
Complex one accepts NADH, while complex two accepts FADH2.