Oxidative Phosphorylation
Oxidative phosphorylation is the process by which energy from fuel oxidation—specifically from
NADH and FADH2 generated during Glycolysis, beta-oxidation, and the TCA cycle—is
transduced into high-energy phosphate bonds of ATP. This process takes place via the electron
transport chain (ETC) system located in the inner mitochondrial membrane.
Why the energy from fuel oxidation is transduced into high-energy phosphate bonds of ATP?
Answer: It is the only way the body can "store" and "transport" the energy released during the
breakdown of nutrients like glucose. Without this transduction, the energy released from oxidation
would simply be lost as heat, which cannot be used to drive cellular work like muscle contraction
or active transport.
The Electron Transport Chain (ETC) is a system of protein complexes and carrier molecules
located in the inner mitochondrial membrane that facilitates the production of ATP. It works by
transferring electrons from energy-rich molecules to oxygen, using the released energy to create
a proton gradient that ultimately drives ATP synthesis.
Five complexes involved in oxidative phosphorylation:
Complex I (NADH-Q reductase):
Oxidizes NADH from glycolysis and the Krebs cycle to NAD+.
It pumps four protons (H+) into the intermembrane space to establish a proton gradient.
Proton gradient: Also called an electrochemical gradient or proton motive force) refers to
a difference in the concentration of hydrogen ions (H+) across the inner mitochondrial
membrane.
Complex II (Succinate dehydrogenase):
Oxidizes FADH2 to FAD.
It contains the FAD binding site and Fe-S centers but does not transport protons across
the membrane.
, Fe-S centers: Fe-S centers are small clusters of iron (Fe) and sulfur (S) atoms found within
the protein complexes of the electron transport chain. Their primary purpose is to act as
carrier for electrons.
i. Electron Carriers: They are specialized for transferring one electron at a time.
ii. Location in Complex II: Succinate dehydrogenase (Complex II) contains three Fe-
S centers located in its "B" subunit.
iii. Pathway: In Complex II, electrons from FADH2 are passed to these Fe-S centers,
which then pass them along to Ubiquinone (Coenzyme Q).
iv. Presence in Other Complexes: They are also found in Complex I (NADH-Q
reductase), where they help bridge the transfer of electrons from NADH to
Ubiquinone.
Complex III (Cytochrome c reductase): Accepts electrons from ubiquinone (Q) and pumps
more protons into the intermembrane space.
Complex IV (Cytochrome c oxidase): An oxygen-requiring step where O2 reacts to
produce H2O. It pumps additional protons into the intermembrane space.
Complex V (ATP Synthase): Uses the energy from the proton electrochemical gradient
(proton motive force) to phosphorylate ADP into ATP.
ATP Calculations
A breakdown of ATP yield per glucose molecule during complete oxidation:
Glycolysis: Produces a net of 2 ATP directly and 2 NADH.
Pyruvate to Acetyl CoA: Produces 2 NADH.
i. Pyruvate and Acetyl CoA are essential chemical intermediates that link the
breakdown of glucose in the cytoplasm to the production of energy inside the
mitochondria.
ii. Pyruvate is a three-carbon molecule that serves as the end product of glycolysis
(the first stage of cellular respiration).
iii. Acetyl CoA is a two-carbon molecule attached to a coenzyme. It is the "fuel" for
the Citric Acid Cycle (also known as the Krebs cycle or TCA cycle).
TCA Cycle: Produces 2 GTP (or ATP), 6 NADH, and 2 FADH2.
i. TCA Cycle (Tricarboxylic Acid Cycle):
Oxidative phosphorylation is the process by which energy from fuel oxidation—specifically from
NADH and FADH2 generated during Glycolysis, beta-oxidation, and the TCA cycle—is
transduced into high-energy phosphate bonds of ATP. This process takes place via the electron
transport chain (ETC) system located in the inner mitochondrial membrane.
Why the energy from fuel oxidation is transduced into high-energy phosphate bonds of ATP?
Answer: It is the only way the body can "store" and "transport" the energy released during the
breakdown of nutrients like glucose. Without this transduction, the energy released from oxidation
would simply be lost as heat, which cannot be used to drive cellular work like muscle contraction
or active transport.
The Electron Transport Chain (ETC) is a system of protein complexes and carrier molecules
located in the inner mitochondrial membrane that facilitates the production of ATP. It works by
transferring electrons from energy-rich molecules to oxygen, using the released energy to create
a proton gradient that ultimately drives ATP synthesis.
Five complexes involved in oxidative phosphorylation:
Complex I (NADH-Q reductase):
Oxidizes NADH from glycolysis and the Krebs cycle to NAD+.
It pumps four protons (H+) into the intermembrane space to establish a proton gradient.
Proton gradient: Also called an electrochemical gradient or proton motive force) refers to
a difference in the concentration of hydrogen ions (H+) across the inner mitochondrial
membrane.
Complex II (Succinate dehydrogenase):
Oxidizes FADH2 to FAD.
It contains the FAD binding site and Fe-S centers but does not transport protons across
the membrane.
, Fe-S centers: Fe-S centers are small clusters of iron (Fe) and sulfur (S) atoms found within
the protein complexes of the electron transport chain. Their primary purpose is to act as
carrier for electrons.
i. Electron Carriers: They are specialized for transferring one electron at a time.
ii. Location in Complex II: Succinate dehydrogenase (Complex II) contains three Fe-
S centers located in its "B" subunit.
iii. Pathway: In Complex II, electrons from FADH2 are passed to these Fe-S centers,
which then pass them along to Ubiquinone (Coenzyme Q).
iv. Presence in Other Complexes: They are also found in Complex I (NADH-Q
reductase), where they help bridge the transfer of electrons from NADH to
Ubiquinone.
Complex III (Cytochrome c reductase): Accepts electrons from ubiquinone (Q) and pumps
more protons into the intermembrane space.
Complex IV (Cytochrome c oxidase): An oxygen-requiring step where O2 reacts to
produce H2O. It pumps additional protons into the intermembrane space.
Complex V (ATP Synthase): Uses the energy from the proton electrochemical gradient
(proton motive force) to phosphorylate ADP into ATP.
ATP Calculations
A breakdown of ATP yield per glucose molecule during complete oxidation:
Glycolysis: Produces a net of 2 ATP directly and 2 NADH.
Pyruvate to Acetyl CoA: Produces 2 NADH.
i. Pyruvate and Acetyl CoA are essential chemical intermediates that link the
breakdown of glucose in the cytoplasm to the production of energy inside the
mitochondria.
ii. Pyruvate is a three-carbon molecule that serves as the end product of glycolysis
(the first stage of cellular respiration).
iii. Acetyl CoA is a two-carbon molecule attached to a coenzyme. It is the "fuel" for
the Citric Acid Cycle (also known as the Krebs cycle or TCA cycle).
TCA Cycle: Produces 2 GTP (or ATP), 6 NADH, and 2 FADH2.
i. TCA Cycle (Tricarboxylic Acid Cycle):
