2. The Electron Transport Chain

Oxidative Phosphorylation

The lecture begins with a recap: The Citric Acid Cycle is the main source of FADH2 and NADH. It’s fed by catabolism of carbs, fats, and proteins.

The final step of catabolism under aerobic conditions is oxidative phosphorylation (OP). During oxidative phosphorylation, NADH and FADH2 get oxidized into NAD+ and FAD. The corresponding release of electrons move through multiple transport steps before reducing the final electron acceptor, oxygen, to form H2O. This is coupled with ATP synthesis.

The Citric Acid Cycle takes places in the matrix of the mitochondrion (in the inner membrane). The FADH2 and NADH produced there cannot diffuse back out. Oxidative Phosphorylation also occurs here.


The mitochondrion is surrounded by a double membrane. The outer membrane is permeable to small molecules and ions. The inner membrane folds into cristae and is impermeable to ions and small molecules. Transporters are required to move these things across this inner membrane. It also includes proteins that help form the Electron Transport Chain (ETC), including the one enzyme responsible for the synthesis of ATP: ATP Synthase.

Chemiosmotic Theory

Credited to Peter Mitchell, 1961. Electrons are transfered through a series of carrier molecules. The electron flow moves “downhill” (exergonic) providing energy to power the uphill transport of protons across the IM from matrix to IMS. The free energy derived from the oxidation of fuel molecules (from the transfer of electrons through the ETC) is conserved as a transmembrane chemical potential called the Proton Motive Force (PMF): the gradient of protons across the membrane is an energy reservoir used to drive ATP synthesis.

ATP is produced when protons flow back into the matrix, down a concentration gradient (exergonic), through ATP Synthase. The ATP Synthase uses the energy harnessed by the proton flow to phosphorylate ADP to produce ATP.

Origin of OP: delivery of electronics to The Electron Transport Chain. The electrons come from the oxidation reaction occurring in a variety of catabolic pathways. These electrons are funneled into the  following Universal Electron Acceptors (UAE).

The Four Universal Electron Acceptors

1. Nicotinamide Adenine Dinucleotide (NAD+)

NAD+ is reduced to an NADH and a proton. Catalyzed by a type of hydrogenase

NAD+ (oxidized) <–> NADH + H+  (reduced)   or…

reduced substrate –(via NAD+ –> NADH + H+)–> oxidized substrate

Taken from the class lecture slide, all rights reserved harvardx, Edx

Example from the Citric Acid Cycle:
malate (C4H6O5) —(malate dehydrogenase)—> oxaloacetate (C4H4O5)

2. Nicotinamide Adenine Dinucleotide Phosphate (NADP+)

From the same family. It’s a phosphorylated version of NAD. Same mechanism as NAD: accepts one proton and two electrons.

NADP+ vs. NAD+:

* NADPH fuels electrons to anabolic reactions (biosynthesis)

* NADH funnels its electrons to the Electron Transport Chain, responsible for catabolic reactions and ATP synthesis.

3. Flavin Adenine Dinucleotide (FAD) derived from vitamin B12. FAD accepts one electron and one proton to form the the semi-reduced NADH, and then captures another electron form the fully reduced FADH2.


4. Flavin Mononucleotude (FMN)

Same two-step process as FAD : reduced substrate + FMN <—> FMNH+ + oxidized substrate

Three of these UAEs–NAD, FAD, and FMN–provide metabolic flexibility and deliver electron and protons to various points in the Electron Transport Chain.




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