[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Fatty acid synthesis (lipogenesis) [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Fatty acid synthesis (lipogenesis) With surplus sugar, the liver and fat tissue build fatty acids two carbons at a time, spending ATP and NADPH, up to palmitate. Updated 2026-11-01 ## Interactive map **Balance:** ATP -7 nadph -14 ## Key facts - Takes place in the cytosol; the rate-limiting step is acetyl-CoA carboxylase (biotin), which forms malonyl-CoA. - Acetyl-CoA leaves the mitochondrion as citrate (citrate shuttle): ATP-citrate lyase splits it again in the cytosol. - Each fatty acid synthase turn: condensation → reduction → dehydration → reduction; adds 2 C. - Palmitate (16 C): 8 acetyl-CoA, 7 ATP and 14 NADPH. - Malonyl-CoA also blocks CPT-I: while fat is being made it is not burned. ## In detail - Citrate shuttle: in the mitochondrion acetyl-CoA and oxaloacetate form citrate, which moves to the cytosol. - In the cytosol ATP-citrate lyase gives back acetyl-CoA and oxaloacetate (one ATP spent). - Oxaloacetate becomes malate and malic enzyme turns it into pyruvate, producing NADPH for synthesis. - ACC carboxylates acetyl-CoA to malonyl-CoA; malonyl/acetyl transacylase loads both onto the ACP of fatty acid synthase. - Seven turns of the cycle give palmitoyl-ACP and the thioesterase releases palmitate; elongation (ER) and desaturases do the rest. - Humans cannot place double bonds beyond carbon 9: linoleic (ω-6) and α-linolenic (ω-3) acids are essential. **Also called** De novo lipogenesis, Fatty acid synthase cycle ## Regulation - Insulin activates ACC (dephosphorylation) and raises ACC and FAS amounts (via SREBP-1c). - Glucagon, adrenaline and AMPK phosphorylate and switch off ACC. - Citrate activates ACC; palmitoyl-CoA inhibits it. ## The steps, one by one - **Entry · [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/)** irreversible [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) + CO₂ + [ATP](https://durgical.com/en/biochemistry/molecules/atp/) → [Malonyl-CoA](https://durgical.com/en/biochemistry/molecules/malonyl-coa/) + ADP + phosphate (Pi) Committed, rate-limiting step: carboxylates acetyl-CoA with bicarbonate to form malonyl-CoA, the two-carbon donor. **If it fails:** Biotin or biotinidase deficiency slows every carboxylase, ACC included. - **Step 1 · [Fatty acid synthase: β-ketoacyl synthase (KS)](https://durgical.com/en/biochemistry/enzymes/fatty-acid-synthase/)** irreversible Acyl-ACP + Malonyl-ACP → β-Ketoacyl-ACP + CO₂ Condensation: the growing acyl chain joins the malonyl loaded on the ACP and the CO₂ added by ACC leaves; the chain gains 2 C. **If it fails:** Losing CO₂ makes the condensation irreversible: that is why ATP is spent at ACC. - **Step 2 · [Fatty acid synthase: β-ketoacyl reductase (KR)](https://durgical.com/en/biochemistry/enzymes/fatty-acid-synthase/)** β-Ketoacyl-ACP + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) ⇌ β-Hydroxyacyl-ACP + NADP⁺ First reduction: NADPH turns the keto group into an alcohol (D-3-hydroxyacyl-ACP). **If it fails:** NADPH comes mainly from the pentose phosphate pathway and malic enzyme: without it synthesis stops. - **Step 3 · [Fatty acid synthase: dehydratase (DH)](https://durgical.com/en/biochemistry/enzymes/fatty-acid-synthase/)** β-Hydroxyacyl-ACP ⇌ trans-Δ²-Enoyl-ACP + H₂O Removes a water molecule and leaves a trans double bond between carbons 2 and 3 (enoyl-ACP). **If it fails:** It mirrors the β-oxidation hydratase, with the opposite isomer (D rather than L). - **Step 4 · [Fatty acid synthase: enoyl reductase (ER)](https://durgical.com/en/biochemistry/enzymes/fatty-acid-synthase/)** irreversible trans-Δ²-Enoyl-ACP + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) → Acyl-ACP + NADP⁺ Second reduction: another NADPH saturates the double bond; an acyl 2 C longer returns to condensation. **If it fails:** After seven turns the acyl has 16 C and moves to the thioesterase. - **Exit · [Fatty acid synthase: thioesterase (TE)](https://durgical.com/en/biochemistry/enzymes/fatty-acid-synthase/)** irreversible Acyl-ACP + H₂O → [Palmitate](https://durgical.com/en/biochemistry/molecules/palmitate/) At 16 carbons the thioesterase cuts the link to the ACP and releases palmitate. **If it fails:** FAS is overexpressed in many tumours, so thioesterase inhibitors are under study. ## Clinical notes - A diet high in refined carbohydrate raises liver lipogenesis and contributes to fatty liver. - Fatty acid synthase is increased in several cancers and is a research target. - Biotin deficiency lowers the activity of ACC and the other carboxylases. ## Pathways - [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) ## Related conditions - [Obesity](https://durgical.com/en/conditions/obesity/) - [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/) - [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) ## Related - [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/) - [Fatty acid synthase (FAS)](https://durgical.com/en/biochemistry/enzymes/fatty-acid-synthase/) - [Malonyl-CoA](https://durgical.com/en/biochemistry/molecules/malonyl-coa/) - [Palmitate (palmitic acid)](https://durgical.com/en/biochemistry/molecules/palmitate/) - [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) - [Citrate](https://durgical.com/en/biochemistry/molecules/citrate/) - [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/) - [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/) ## Test yourself Think of the answer, then tap the question to see it. ## What is the rate-limiting step of fatty acid synthesis and which vitamin does it need? Acetyl-CoA carboxylase, which forms malonyl-CoA; it uses biotin (B7). ## How does acetyl-CoA leave the mitochondrion to make fat? As citrate; in the cytosol ATP-citrate lyase splits it back into acetyl-CoA and oxaloacetate. ## How much NADPH is spent to make one palmitate? 14 NADPH: two for each of the seven turns (one per reduction). ## Why do synthesis and β-oxidation not run at the same time? Malonyl-CoA from synthesis inhibits CPT-I, so acyl-CoA cannot enter the mitochondrion. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/fatty-acid-synthesis/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Fatty acyl-CoA biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-75105) (Reactome, 2026); [Fatty acid metabolism](https://reactome.org/PathwayBrowser/#/R-HSA-8978868) (Reactome, 2026); [FASN: Fatty acid synthase (human)](https://www.uniprot.org/uniprotkb/P49327/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/pathways/fatty-acid-synthesis/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/fatty-acid-synthesis/