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Pathway

Fatty acid synthesis

Homo sapiens · Cytosol · 6 reactions

In the fed state, cytosolic acetyl-CoA is converted to malonyl-CoA. Fatty acid synthase uses an acetyl primer, repeated malonyl additions, and NADPH to build palmitate, which can then be elongated or desaturated.

REACTOME IDENTIFIERR-HSA-75105View source record ↗

Pathway scope

NETWORK MAP

The FASN cycle is grouped; this map does not sum seven elongation rounds or the ATP cost of making malonyl-CoA.

Overview

EXPLORE BY LEVEL

Fatty acid synthesis is a set of connected chemical steps in human cells. In the fed state, cytosolic acetyl-CoA is converted to malonyl-CoA. Fatty acid synthase uses an acetyl primer, repeated malonyl additions, and to build palmitate, which can then be elongated or desaturated.

WHY THE FLOW CHANGES

Regulation

Compare fed and fasting

Acetyl-CoA carboxylase links fuel abundance to fatty-acid building.

Can speed upCitrate

Citrate can allosterically activate acetyl-CoA carboxylase.

Can slow downAMPK phosphorylation and long-chain acyl-CoA

Energy stress and fatty-acid products restrain acetyl-CoA carboxylase.

Context mattersInsulin in fed tissues

Insulin favors lipogenic enzyme activity and expression, especially in liver and adipose tissue.

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. Cytosolic acetyl-CoA

    Citrate export and ATP-citrate lyase supply acetyl-CoA outside mitochondria.

    1. Step 1Irreversible · ATP → ADP + Pi

  2. Malonyl-CoA formation

    Acetyl-CoA carboxylase makes the activated two-carbon donor for synthesis.

    1. Step 2Irreversible · HCO3− + ATP → ADP + Pi

  3. Fatty acid synthase cycle

    Condensation, reduction, dehydration, and a second reduction extend the chain.

    1. Step 3Irreversible
    2. Step 4Irreversible · CoA → CO2
    3. Step 5Irreversible · NADPH → NADP+

  4. Palmitate release

    After seven elongation rounds, the thioesterase domain releases palmitate.

    1. Step 6Irreversible

Reaction steps

1Cytosolic acetyl-CoA supplyCitrate + Coenzyme A → Acetyl-CoA + OxaloacetateIrreversible

ATP-citrate lyase provides cytosolic acetyl-CoA from exported citrate.

REACTION · PER TURN + + yields + + +
Enzyme
EC 2.3.3.8 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per citrate
Once
Stage
Cytosolic acetyl-CoA
MECHANISM & CONTEXT

Acetyl-CoA itself cannot cross the inner mitochondrial membrane. Citrate carries acetyl units to the cytosol, where ATP-citrate lyase regenerates acetyl-CoA for lipid synthesis.

Evidence for this step: Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

2Malonyl-CoA formationAcetyl-CoA → Malonyl-CoAIrreversible

Acetyl-CoA carboxylase uses ATP and biotin to make malonyl-CoA.

REACTION · PER TURN + + yields + +
Enzyme
EC 6.4.1.2 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per citrate
Once
Stage
Malonyl-CoA formation
MECHANISM & CONTEXT

This committed step is regulated by phosphorylation, citrate, and long-chain acyl-CoA signals.

Evidence for this step: Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

3Acetyl primer loadingAcetyl-CoA → Growing fatty acyl-ACPIrreversible

The acetyl primer is loaded onto the acyl carrier protein of fatty acid synthase.

REACTION · PER TURNyields
Enzyme
EC 2.3.1.85 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per citrate
Once
Stage
Fatty acid synthase cycle
MECHANISM & CONTEXT

The map tracks the acetyl group on the carrier protein and omits the enzyme-bound phosphopantetheine arm. A growing acyl chain is carried through successive catalytic domains of the FASN dimer.

Evidence for this step: Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

4Malonyl condensationGrowing fatty acyl-ACP + Malonyl-CoA → 3-Ketoacyl-ACPIrreversible

Decarboxylative condensation adds two carbons from malonyl-CoA.

REACTION · PER TURN + + yields +
Enzyme
EC 2.3.1.85 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per citrate
Once
Stage
Fatty acid synthase cycle
MECHANISM & CONTEXT

Carbon dioxide released during condensation is the carbon previously added by acetyl-CoA carboxylase; this coupling helps drive chain elongation.

Evidence for this step: Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

5Reduction, dehydration, and second reduction3-Ketoacyl-ACP → Growing fatty acyl-ACPIrreversible

FASN reduces the keto group, removes water, and reduces the double bond to yield a saturated chain two carbons longer.

REACTION · PER TURN + yields +
Enzyme
EC 2.3.1.85 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per citrate
Once
Stage
Fatty acid synthase cycle
MECHANISM & CONTEXT

These three catalytic activities are grouped into one map step per elongation round. Seven such rounds follow primer loading to produce palmitate.

Evidence for this step: Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

6Palmitate releaseGrowing fatty acyl-ACP → PalmitateIrreversible

FASN thioesterase releases palmitate, its principal product.

REACTION · PER TURNyields
Enzyme
EC 2.3.1.85 ↗
Cofactors
No metal cofactor listed.
Reversibility
Irreversible under cellular conditions. This is a control point.
Runs per citrate
Once
Stage
Palmitate release
MECHANISM & CONTEXT

The free fatty acid can be activated to palmitoyl-CoA, elongated, or desaturated; those downstream reactions are not part of the FASN core cycle.

Evidence for this step: Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

Research sources, claims, and curation

Fatty acyl-CoA biosynthesis and palmitate synthesis (R-HSA-75105)

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

Claims

In the fed state, cytosolic acetyl-CoA is converted to malonyl-CoA. Fatty acid synthase uses an acetyl primer, repeated malonyl additions, and NADPH to build palmitate, which can then be elongated or desaturated.

Curation notes

  • The FASN condensation and reduction, dehydration, and second reduction are grouped; seven cycles are required to produce palmitate from one acetyl primer and seven malonyl units.
  • Citrate export supplies acetyl units to the cytosol, where ATP-citrate lyase forms acetyl-CoA for fatty-acid synthesis.
  • The high-level map is not a fully balanced palmitate-synthesis equation; the displayed cofactor use is per illustrated elongation round.