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Pathway

Oxidative phosphorylation

Homo sapiens · Inner mitochondrial membrane · 5 reactions

The respiratory chain transfers electrons from NADH and FAD-linked sources to oxygen. Complexes I, III, and IV pump protons; ATP synthase uses the proton-motive force to make ATP from ADP and phosphate.

REACTOME IDENTIFIERR-HSA-611105View source record ↗

Pathway scope

NETWORK MAP

Electron transport and proton coupling are shown schematically; exact proton and ATP stoichiometry depends on coupling and transport costs.

Overview

EXPLORE BY LEVEL

Oxidative is a set of connected chemical steps in human cells. The respiratory chain transfers electrons from and FAD-linked sources to oxygen. Complexes I, III, and IV pump protons; uses the proton-motive force to make ATP from ADP and phosphate.

WHY THE FLOW CHANGES

Regulation

Compare fed and fasting

ADP availability is a major signal for mitochondrial ATP production.

Can speed upADP and phosphate

When ATP is used, ADP and phosphate availability can increase ATP synthesis and electron transport.

Can slow downHigh ATP / low ADP

Low demand slows ATP synthase and, in turn, electron transport.

Context mattersOxygen

Oxygen accepts electrons at complex IV; limited oxygen constrains respiratory ATP production.

How to read this map

This is an instructional map of selected reactions, not a complete inventory of every reaction in the body. Some steps are grouped; transport, alternate routes, tissue differences, or full molecule balances may be summarized. The Research notes explain this map’s specific limits.

Explore the reaction map and enzyme steps

Pathway map

GENERATED FROM STRUCTURED REACTIONS

Select a molecule or enzyme to inspect it. Select a step number to open its full reaction detail.

  1. NADH entry

    Complex I oxidizes NADH and reduces ubiquinone while pumping protons.

    1. Step 1Irreversible
    2. Step 2Irreversible

  2. Electron transfer to oxygen

    Complex III and cytochrome c relay electrons to complex IV, where oxygen is reduced to water.

    1. Step 3Irreversible
    2. Step 4Irreversible · H+ → —

  3. ATP synthesis

    Proton return through ATP synthase drives phosphorylation of ADP.

    1. Step 5Irreversible · Pi + H+ → H2O

Reaction steps

1NADH oxidation at complex INADH + Ubiquinone → NAD+ + UbiquinolIrreversible

Complex I transfers electrons from NADH to ubiquinone and pumps protons.

REACTION · PER TURN + yields +
Enzyme
EC 7.1.1.2 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per nadh
Once
Stage
NADH entry
MECHANISM & CONTEXT

The electron-transfer reaction is coupled to proton translocation from the matrix to the intermembrane-space side of the membrane.

Evidence for this step: Respiratory electron transport (R-HSA-611105) · ATP formation by chemiosmotic coupling (R-HSA-163210)

2Succinate-linked electron entrySuccinate + Ubiquinone → Fumarate + UbiquinolIrreversible

Complex II transfers succinate-derived electrons to ubiquinone without pumping protons.

REACTION · PER TURN + yields +
Enzyme
EC 1.3.5.1 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per nadh
Once
Stage
NADH entry
MECHANISM & CONTEXT

This link illustrates the FAD-dependent entry point; complex II itself is also part of the TCA cycle.

Evidence for this step: Respiratory electron transport (R-HSA-611105) · ATP formation by chemiosmotic coupling (R-HSA-163210)

3Ubiquinol oxidation at complex IIIUbiquinol + Cytochrome c (oxidized) → Ubiquinone + Cytochrome c (reduced)Irreversible

Complex III passes electrons from ubiquinol to cytochrome c and contributes to proton translocation.

REACTION · PER TURN + yields +
Enzyme
EC 7.1.1.8 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per nadh
Once
Stage
Electron transfer to oxygen
MECHANISM & CONTEXT

The Q cycle moves electrons one at a time to cytochrome c while coupling redox chemistry to proton movement.

Evidence for this step: Respiratory electron transport (R-HSA-611105) · ATP formation by chemiosmotic coupling (R-HSA-163210)

4Oxygen reduction at complex IVCytochrome c (reduced) + Molecular oxygen → Cytochrome c (oxidized) + WaterIrreversible

Cytochrome c oxidase transfers four electrons to one oxygen molecule and forms two waters.

REACTION · PER TURN + + yields +
Enzyme
EC 7.1.1.9 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per nadh
Once
Stage
Electron transfer to oxygen
MECHANISM & CONTEXT

Oxygen is the terminal electron acceptor. Four reduced cytochrome c molecules supply the four electrons; the displayed proton count represents matrix protons consumed in water formation, while proton pumping is described separately.

Evidence for this step: Respiratory electron transport (R-HSA-611105) · ATP formation by chemiosmotic coupling (R-HSA-163210)

5ATP synthesis by chemiosmosisADP → ATPIrreversible

ATP synthase uses proton flow to drive ATP formation from ADP and phosphate.

REACTION · PER TURN + + yields +
Enzyme
EC 7.1.2.2 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per nadh
Once
Stage
ATP synthesis
MECHANISM & CONTEXT

The exact proton cost per ATP depends on the c-ring stoichiometry and the transport costs for phosphate and adenine nucleotides. The diagram is qualitative and does not calculate a P/O ratio.

Evidence for this step: Respiratory electron transport (R-HSA-611105) · ATP formation by chemiosmotic coupling (R-HSA-163210)

Research sources, claims, and curation

Respiratory electron transport (R-HSA-611105)

Reactome · Homo sapiens · Reviewed Reactome human pathway used for reaction sequence and context.

ATP formation by chemiosmotic coupling (R-HSA-163210)

Reactome · Homo sapiens · Related reviewed Reactome pathway used to cross-check this route.

Claims

The respiratory chain transfers electrons from NADH and FAD-linked sources to oxygen. Complexes I, III, and IV pump protons; ATP synthase uses the proton-motive force to make ATP from ADP and phosphate.

Curation notes

  • Electron carriers and proton movement are schematic; individual proton stoichiometries are not fully balanced here.
  • The P/O ratio is not shown because it depends on coupling and transport costs; common estimates are approximate rather than a fixed yield.
  • Reactome separates respiratory electron transport and chemiosmotic ATP formation into reviewed pathway records.