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Pathway

Fatty acid β-oxidation

Homo sapiens · Mitochondrial matrix · 5 reactions

Mitochondrial beta-oxidation repeatedly oxidizes, hydrates, oxidizes again, and cleaves fatty acyl-CoA. Each complete turn shortens the chain by two carbons and yields acetyl-CoA, NADH, and electrons that reach ubiquinone.

REACTOME IDENTIFIERR-HSA-77289View source record ↗

Pathway scope

NETWORK MAP

One representative turn is shown; complete palmitate breakdown requires seven turns and is not summed here.

Overview

EXPLORE BY LEVEL

Fatty acid β-oxidation is a set of connected chemical steps in human cells. Mitochondrial beta-oxidation repeatedly oxidizes, hydrates, oxidizes again, and cleaves fatty acyl-CoA. Each complete turn shortens the chain by two carbons and yields acetyl-CoA, , and electrons that reach ubiquinone.

WHY THE FLOW CHANGES

Regulation

Compare fed and fasting

Fatty-acid entry into mitochondria is a major control point.

Can slow downMalonyl-CoA

Malonyl-CoA inhibits CPT1, limiting long-chain fatty-acid entry into mitochondria.

Can speed upLow insulin and increased fatty-acid supply

During fasting, adipose lipolysis supplies fatty acids to tissues; pathway use still depends on tissue and demand.

Context mattersEnergy demand and carnitine transport

Mitochondrial uptake and downstream respiratory capacity also shape oxidation rate.

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. Mitochondrial entry

    Long-chain fatty acids are activated and transferred through the carnitine shuttle before the spiral.

    1. Step 1Irreversible

  2. Four-step beta-oxidation spiral

    Each turn contains two oxidations, a hydration, and thiolysis; the shortened acyl-CoA repeats the sequence.

    1. Step 2Irreversible · FAD → FADH2
    2. Step 3Irreversible · H2O → —
    3. Step 4Irreversible · NAD+ → NADH + H+
    4. Step 5Irreversible · CoA → —

Reaction steps

1Carnitine-dependent import (summary)Palmitoyl-CoA → Palmitoyl-CoAIrreversible

The carnitine shuttle transfers long-chain acyl groups into the mitochondrial matrix.

REACTION · PER TURNyields
Enzyme
EC 2.3.1.21 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per palmitoyl-coa
Once
Stage
Mitochondrial entry
MECHANISM & CONTEXT

The shuttle is summarized as transport because acyl-carnitine and the individual translocase steps are outside this four-reaction chemical spiral.

Evidence for this step: Mitochondrial fatty acid beta-oxidation (R-HSA-77289)

2First oxidationPalmitoyl-CoA → trans-2-Enoyl-CoAIrreversible

Acyl-CoA dehydrogenase forms a trans double bond between alpha and beta carbons.

REACTION · PER TURN + yields +
Enzyme
EC 1.3.8.9 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per palmitoyl-coa
Once
Stage
Four-step beta-oxidation spiral
MECHANISM & CONTEXT

Electrons pass from enzyme-bound FAD through electron-transfer flavoprotein toward ubiquinone. This representative turn begins with palmitoyl-CoA; subsequent turns use progressively shorter acyl-CoA substrates.

Evidence for this step: Mitochondrial fatty acid beta-oxidation (R-HSA-77289)

3Hydrationtrans-2-Enoyl-CoA → L-3-Hydroxyacyl-CoAIrreversible

Enoyl-CoA hydratase adds water to form L-3-hydroxyacyl-CoA.

REACTION · PER TURN + yields
Enzyme
EC 4.2.1.17 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per palmitoyl-coa
Once
Stage
Four-step beta-oxidation spiral
MECHANISM & CONTEXT

The reaction sets the stereochemistry for the next oxidation.

Evidence for this step: Mitochondrial fatty acid beta-oxidation (R-HSA-77289)

4Second oxidationL-3-Hydroxyacyl-CoA → 3-Ketoacyl-CoAIrreversible

The hydroxyacyl intermediate is oxidized to 3-ketoacyl-CoA, producing NADH.

REACTION · PER TURN + yields + +
Enzyme
EC 1.1.1.211 ↗
Cofactors
NAD+ is consumed as a co-substrate (see reaction).
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per palmitoyl-coa
Once
Stage
Four-step beta-oxidation spiral
MECHANISM & CONTEXT

Long-chain substrates are handled by the mitochondrial trifunctional protein; shorter chains use other dehydrogenases.

Evidence for this step: Mitochondrial fatty acid beta-oxidation (R-HSA-77289)

5Thiolytic cleavage3-Ketoacyl-CoA → Acetyl-CoA + Shortened fatty acyl-CoAIrreversible

Thiolase releases one acetyl-CoA and a fatty acyl-CoA shortened by two carbons.

REACTION · PER TURN + yields +
Enzyme
EC 2.3.1.16 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per palmitoyl-coa
Once
Stage
Four-step beta-oxidation spiral
MECHANISM & CONTEXT

The shortened chain re-enters the spiral. Unsaturated and odd-chain fatty acids require additional enzymes and have different endpoints.

Evidence for this step: Mitochondrial fatty acid beta-oxidation (R-HSA-77289)

Research sources, claims, and curation

Mitochondrial fatty acid beta-oxidation (R-HSA-77289)

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

Claims

Mitochondrial beta-oxidation repeatedly oxidizes, hydrates, oxidizes again, and cleaves fatty acyl-CoA. Each complete turn shortens the chain by two carbons and yields acetyl-CoA, NADH, and electrons that reach ubiquinone.

Curation notes

  • This page models one representative turn of the four recurring chemical steps in mitochondrial beta-oxidation.
  • The palmitoyl-CoA input is already activated. Fatty-acid activation costs ATP before beta-oxidation and is not included in the spiral.
  • Peroxisomal oxidation of very-long-chain fatty acids and auxiliary routes for unsaturated or odd-chain fatty acids are outside this initial map.