[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Fatty acid β-oxidation [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Fatty acid β-oxidation When fasting, mitochondria cut fatty acids two carbons at a time: they give acetyl-CoA, NADH and FADH₂ and far more energy than glucose. Updated 2026-11-01 ## Interactive map **Balance:** FADH₂ +7 NADH +7 ## Key facts - Takes place in the mitochondrial matrix; long-chain fatty acids enter through the carnitine shuttle (CPT-I is the regulated step). - Each turn: oxidation (FAD) → hydration → oxidation (NAD⁺) → thiolysis; 1 acetyl-CoA leaves. - Palmitate (16 C): 7 turns → 8 acetyl-CoA, 7 FADH₂ and 7 NADH; about 106 net ATP (108 minus 2 for activation). - Malonyl-CoA inhibits CPT-I: fat synthesis and oxidation do not run together. - Medium-chain fatty acids (MCT) enter without carnitine; very-long-chain ones start in the peroxisome. ## In detail - Activation: on the outer membrane acyl-CoA synthetase forms acyl-CoA (ATP → AMP + PPi). - CPT-I (outer membrane) swaps CoA for carnitine: acylcarnitine. This is the step malonyl-CoA blocks. - Carnitine-acylcarnitine translocase (CACT) exchanges acylcarnitine inwards for free carnitine outwards. - CPT-II (inner face of the inner membrane) puts CoA back: acyl-CoA in the matrix and free carnitine. - In the matrix the four reactions repeat until the whole chain is split into acetyl-CoA. - Unsaturated: need an isomerase (and a 2,4-dienoyl-CoA reductase using NADPH). Odd-chain: the last turn leaves propionyl-CoA. **Also called** Mitochondrial beta-oxidation, Lynen spiral ## Regulation - Glucagon and adrenaline activate hormone-sensitive lipase and raise the free fatty acids reaching liver and muscle. - Insulin slows lipolysis and, through ACC and malonyl-CoA, closes entry at CPT-I. - Fasting and PPARα raise β-oxidation enzymes; high NADH or acetyl-CoA slows it. ## The steps, one by one - **Entry · Long-chain acyl-CoA synthetase (ACSL)** irreversible [Palmitate](https://durgical.com/en/biochemistry/molecules/palmitate/) + coenzyme A + [ATP](https://durgical.com/en/biochemistry/molecules/atp/) → Acyl-CoA + AMP + pyrophosphate Activates the fatty acid in the cytosol by linking it to CoA; spends two high-energy bonds (ATP → AMP). It then enters through the carnitine shuttle. **If it fails:** Entry into the mitochondrion (CPT-I, translocase, CPT-II) is where carnitine and CPT-II deficiencies fail. - **Step 1 · [Acyl-CoA dehydrogenase (VLCAD, MCAD, SCAD by chain length)](https://durgical.com/en/biochemistry/enzymes/medium-chain-acyl-coa-dehydrogenase/)** irreversible Acyl-CoA + [FAD](https://durgical.com/en/biochemistry/molecules/fad/) → trans-Δ²-Enoyl-CoA + fadh2 First oxidation: makes a trans double bond between C2 and C3; the electrons go to FAD and then, through ETF, to ubiquinone. **If it fails:** MCAD deficiency is the most common β-oxidation defect: hypoketotic hypoglycaemia on fasting. Hypoglycin blocks this same enzyme. [Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency →](https://durgical.com/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/) - **Step 2 · Enoyl-CoA hydratase** trans-Δ²-Enoyl-CoA + H₂O ⇌ L-3-Hydroxyacyl-CoA Adds water across the double bond and forms L-3-hydroxyacyl-CoA. **If it fails:** For long chains this activity and the next two are carried out by the mitochondrial trifunctional protein (HADHA/HADHB). - **Step 3 · 3-Hydroxyacyl-CoA dehydrogenase (HADH; LCHAD for long chains)** L-3-Hydroxyacyl-CoA + [NAD⁺](https://durgical.com/en/biochemistry/molecules/nad/) ⇌ 3-Ketoacyl-CoA + NADH Second oxidation: the alcohol becomes a keto group and NADH is formed. **If it fails:** LCHAD deficiency: hypoglycaemia, cardiomyopathy and retinopathy; the mother of an affected fetus can develop acute fatty liver of pregnancy or HELLP syndrome. - **Step 4 · β-Ketothiolase (3-ketoacyl-CoA thiolase)** 3-Ketoacyl-CoA + coenzyme A ⇌ Acyl-CoA + [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) A new CoA cuts off the last two carbons: one acetyl-CoA leaves and an acyl-CoA 2 C shorter starts again. **If it fails:** The acetyl-CoA goes to the Krebs cycle or, in the fasting liver, to ketone bodies. ## Clinical notes - β-Oxidation defects (MCAD, VLCAD, LCHAD, CPT-II, carnitine) cause hypoketotic hypoglycaemia during fasting or fever. - The tandem mass spectrometry acylcarnitine profile in newborn screening detects many of them. - Ackee hypoglycin inhibits acyl-CoA dehydrogenases: severe hypoglycaemia (Jamaican vomiting sickness). - At rest the heart gets most of its ATP from β-oxidation. ## Pathways - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Ketogenesis (ketone body synthesis)](https://durgical.com/en/biochemistry/pathways/ketogenesis/) - [Fatty acid synthesis (lipogenesis)](https://durgical.com/en/biochemistry/pathways/fatty-acid-synthesis/) ## Related conditions - [Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency](https://durgical.com/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/) - [Primary carnitine deficiency](https://durgical.com/en/conditions/primary-carnitine-deficiency/) - [Carnitine palmitoyltransferase II (CPT-II) deficiency](https://durgical.com/en/conditions/carnitine-palmitoyltransferase-ii-deficiency/) - [Jamaican vomiting sickness (ackee poisoning)](https://durgical.com/en/conditions/jamaican-vomiting-sickness/) - [Diabetic ketoacidosis](https://durgical.com/en/conditions/diabetic-ketoacidosis/) ## Related - [Carnitine palmitoyltransferase I (CPT-I)](https://durgical.com/en/biochemistry/enzymes/carnitine-palmitoyltransferase-i/) - [Medium-chain acyl-CoA dehydrogenase (MCAD)](https://durgical.com/en/biochemistry/enzymes/medium-chain-acyl-coa-dehydrogenase/) - [Carnitine (L-carnitine)](https://durgical.com/en/biochemistry/molecules/carnitine/) - [Palmitate (palmitic acid)](https://durgical.com/en/biochemistry/molecules/palmitate/) - [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) - [Carnitine shuttle](https://durgical.com/en/biochemistry/topics/carnitine-shuttle/) - [Malonyl-CoA](https://durgical.com/en/biochemistry/molecules/malonyl-coa/) - [Hormone-sensitive lipase (HSL)](https://durgical.com/en/biochemistry/enzymes/hormone-sensitive-lipase/) - [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/) - [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Ketogenesis (ketone body synthesis)](https://durgical.com/en/biochemistry/pathways/ketogenesis/) - [Odd-chain fatty acids and propionate metabolism](https://durgical.com/en/biochemistry/topics/odd-chain-fatty-acids-and-propionate-metabolism/) - [Peroxisomal oxidation (β- and α-oxidation)](https://durgical.com/en/biochemistry/topics/peroxisomal-oxidation/) ## Test yourself Think of the answer, then tap the question to see it. ## What does each turn of β-oxidation yield? 1 FADH₂, 1 NADH and 1 acetyl-CoA, and the acyl-CoA becomes 2 carbons shorter. ## How many turns does palmitate need and how many acetyl-CoA does it give? 7 turns and 8 acetyl-CoA, because the last turn splits a 4-C piece in two. ## Which molecule blocks fatty acid entry into the mitochondrion? Malonyl-CoA, which inhibits carnitine palmitoyltransferase I (CPT-I). ## Why do β-oxidation defects cause hypoglycaemia with low ketones? Without acetyl-CoA from fat the liver makes no ketones and lacks energy for gluconeogenesis, while tissues burn more glucose. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/fatty-acid-oxidation/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Mitochondrial Fatty Acid Beta-Oxidation](https://reactome.org/PathwayBrowser/#/R-HSA-77289) (Reactome, 2026); [mitochondrial fatty acid beta-oxidation of saturated fatty acids](https://reactome.org/PathwayBrowser/#/R-HSA-77286) (Reactome, 2026); [Carnitine shuttle](https://reactome.org/PathwayBrowser/#/R-HSA-200425) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). 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