● Amino acids, sugars, and lipids feed into the TCA cycle

● The TCA products are as follows:

○ Carbon dioxide
○ NADH
○ FADH2
○ ATP

The Electron Transport Chain

● The goal of the electron transport chain is to use NADH and FADH2 to concentrate H+
protons in the intermembrane space
● Electrochemical potential is generated across this membrane in the mitochondria- Inner
mitochondrial membrane
● Electron transport across the inner mitochondrial membrane creates a proton gradient
which is used to fuel ATP synthesis
● The energy provided by the oxidation of NADH into NAD+
○ Instead of ATP, the ETC uses electrons from NADH or FADH2
○ The hydride ion is removed from NADH (to regenerate NAD+) and is converted
into a proton and two electrons (H-→ H+ + 2e -)
● The ETC converts NADH reduction into a gradient of protons
○ The electrons start with very high energy and gradually lose it as they pass along
the chain.
○ Electrons pass sequentially from one complex to another until they are finally
transferred to oxygen
● The ETC requires the close association of the electron carriers with protein
molecules.The electron carriers are prosthetic groups
○ Prosthetic groups are large non-protein molecules embedded in the protein
○ Complicated chemical structures not possible with amino acids
 ○ Flavin mononucleotide (comes from Vitamin B2)
● Example: Heme is the prosthetic group in hemoglobin and is necessary for oxygen
binding
● Complex I receives 2 electrons from NADH and passes them to CoQ. The energy is
used to pump 4 H+
● Coenzyme Q (CoQ) is a lipid-like carrier (aka ubiquinone)
● Coenzyme Q is also known as Succinate dehydrogenase
● Complex II receives 2 electrons from succinate passing them directly to FADH2 and then
into CoQ. Does not pump H+.
● Complex III receives 2 electrons from CoQ and passes them to Cytochrome C. The
energy is used to pump 4 H+
● Cytochrome c is a small protein that serves as carrier of electrons
○ CytC moves Electrons from complex 3 to 4
○ CytC is a small protein with a Heme cofactor
○ Heme is the electron carrier
● Complex IV receives 2 electrons from Cytochrome C and passes them to Oxygen, which
is reduced to water. The energy is used to pump 2 H+
● Electrons move in a single direction because Redox centers (electron carriers) are
organized from low to high affinity
● The redox centers and the H+ pumps are separated in complex I (Electron transport and
Tandem Proton pumping)
● Structural changes in Complex I direct H+ to move through translocation half-channels
○ Half-channels are formed by conserved polar residues and polar cavities
containing water molecules
● Structural changes in Complex I direct H+ to move through translocation half-channels
● The ETC forms supramolecular assemblies or supercomplexes- meaning that the
complexes are clustered together
● Finally, the H+ flow back powering the synthesis of ATP
○ The power source for the ATP synthase is a difference in the concentration of H+
on opposite sides of the inner mitochondrial membrane.
○ Protons flow down their concentration gradient into the matrix through the
membrane protein ATP synthase, causing it to spin
○ ATP synthesis takes place in the ATP synthase complex of the Electron transport
chain, which is found in the inner mitochondrial membrane. It is fuelled by the
proton gradient created by oxidation of high energy molecules such as NADH
and FADH2.