[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Classic bile acid synthesis pathway [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Classic bile acid synthesis pathway The liver turns cholesterol into bile acids, which help digest fat. It is also the main way the body gets rid of cholesterol. Updated 2026-11-01 ## Interactive map ## Key facts - Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting step; bile acids returning from the gut repress it (FXR–SHP and FGF19). - The primary bile acids are cholic acid (needs 12α-hydroxylation by CYP8B1) and chenodeoxycholic acid (made without it). - Conjugation with glycine or taurine (BAAT) lowers the pKa, so bile salts stay ionised and soluble in the intestine. - About 95% of bile acids are reabsorbed in the terminal ileum and return to the liver (enterohepatic circulation). - Gut bacteria deconjugate and 7α-dehydroxylate them to the secondary bile acids, deoxycholic and lithocholic acid. ## Regulation - Bile acids activate FXR in hepatocytes (SHP) and in the ileum (FGF19), and both signals repress CYP7A1. - Insulin, the fed state and a daily rhythm change CYP7A1 activity. - Bile acid sequestrants interrupt the return to the liver, so CYP7A1 rises and the liver uses more cholesterol, lowering LDL. ## The steps, one by one - **Step 1 · [Cholesterol 7α-hydroxylase (CYP7A1)](https://durgical.com/en/biochemistry/enzymes/cholesterol-7-hydroxylase/)** irreversible [Cholesterol](https://durgical.com/en/biochemistry/molecules/cholesterol/) + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) + o2 → 7α-Hydroxycholesterol + nadp + H₂O In the endoplasmic reticulum it adds a 7α-hydroxyl to cholesterol: the committed and slowest step. **If it fails:** CYP7A1 deficiency (rare): high LDL cholesterol and early gallstones that respond poorly to statins. [Gallstones (cholelithiasis) →](https://durgical.com/en/conditions/gallstones/) - **Step 2 · 3β-Hydroxy-Δ5-C27-steroid dehydrogenase (HSD3B7)** irreversible 7α-Hydroxycholesterol + [NAD⁺](https://durgical.com/en/biochemistry/molecules/nad/) → 7α-Hydroxy-4-cholesten-3-one (C4) + NADH Oxidises the 3-hydroxyl and shifts the double bond to ring A, giving C4, whose blood level mirrors how fast bile acids are being made. **If it fails:** HSD3B7 deficiency: neonatal cholestasis and poor absorption of fat-soluble vitamins; it responds to oral primary bile acids. - **Step 3 · Sterol 12α-hydroxylase (CYP8B1)** irreversible 7α-Hydroxy-4-cholesten-3-one (C4) + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) + o2 → 7α,12α-Dihydroxy-4-cholesten-3-one + nadp + H₂O Adds the 12α-hydroxyl that defines cholic acid; intermediates that skip this step become chenodeoxycholic acid. **If it fails:** Its activity sets the ratio of cholic to chenodeoxycholic acid; no classic human deficiency disease is described. - **Step 4 · Δ4-3-Oxosteroid 5β-reductase (AKR1D1), then 3α-hydroxysteroid dehydrogenase (AKR1C4)** irreversible 7α,12α-Dihydroxy-4-cholesten-3-one + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) → 5β-Cholestane-3α,7α,12α-triol + nadp Saturates ring A in the 5β orientation and reduces the 3-oxo group to a 3α-hydroxyl, giving the bent shape typical of bile acids. **If it fails:** AKR1D1 deficiency: neonatal cholestasis with abnormal Δ4-3-oxo bile acids; it responds to primary bile acids. - **Step 5 · Sterol 27-hydroxylase (CYP27A1) and peroxisomal side-chain shortening** irreversible 5β-Cholestane-3α,7α,12α-triol + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) + o2 → Choloyl-CoA + [Propionyl-CoA](https://durgical.com/en/biochemistry/molecules/propionyl-coa/) Mitochondrial CYP27A1 oxidises the end of the side chain to a carboxylic acid, and in the peroxisome one round of β-oxidation removes three carbons as propionyl-CoA, leaving choloyl-CoA. **If it fails:** CYP27A1 deficiency causes cerebrotendinous xanthomatosis; peroxisomal disorders such as Zellweger syndrome leave C27 bile acid intermediates. [Zellweger syndrome (Zellweger spectrum) →](https://durgical.com/en/conditions/zellweger-syndrome/) - **Step 6 · Bile acid-CoA:amino acid N-acyltransferase (BAAT)** irreversible Choloyl-CoA + Glycine (or taurine) → Glycocholic acid (taurocholic acid with taurine) + coenzyme A Joins glycine or taurine to choloyl-CoA, making the bile salts that are secreted into bile. **If it fails:** BAAT deficiency leaves bile acids unconjugated: fat and fat-soluble vitamin malabsorption with itching. ## Clinical notes - Gallstones form when bile carries too much cholesterol for its bile salts and phospholipids. - Loss of the terminal ileum (resection or Crohn disease) wastes bile acids: bile acid diarrhoea and fat malabsorption. - Cerebrotendinous xanthomatosis (CYP27A1): tendon xanthomas, cataracts, chronic diarrhoea and neurological decline; it is treated with chenodeoxycholic acid. - Peroxisomal disorders such as Zellweger syndrome block side-chain shortening, and C27 bile acid intermediates accumulate. ## Pathways - [Classic bile acid synthesis pathway](https://durgical.com/en/biochemistry/pathways/classic-bile-acid-synthesis-pathway/) ## Related conditions - [Gallstones (cholelithiasis)](https://durgical.com/en/conditions/gallstones/) - [Zellweger syndrome (Zellweger spectrum)](https://durgical.com/en/conditions/zellweger-syndrome/) - [Crohn disease](https://durgical.com/en/conditions/crohn-disease/) - [Cataract](https://durgical.com/en/conditions/cataract/) ## Related - [Cholesterol](https://durgical.com/en/biochemistry/molecules/cholesterol/) - [Cholic acid](https://durgical.com/en/biochemistry/molecules/cholic-acid/) - [Cholesterol 7α-hydroxylase (CYP7A1)](https://durgical.com/en/biochemistry/enzymes/cholesterol-7-hydroxylase/) - [Bile acid synthesis](https://durgical.com/en/biochemistry/topics/bile-acid-synthesis/) - [Cholesterol synthesis (mevalonate pathway)](https://durgical.com/en/biochemistry/pathways/cholesterol-synthesis/) - [HMG-CoA reductase](https://durgical.com/en/biochemistry/enzymes/hmg-coa-reductase/) - [Peroxisomal oxidation (β- and α-oxidation)](https://durgical.com/en/biochemistry/topics/peroxisomal-oxidation/) - [Propionyl-CoA](https://durgical.com/en/biochemistry/molecules/propionyl-coa/) - [Lipoprotein metabolism](https://durgical.com/en/biochemistry/topics/lipoprotein-metabolism/) - [Adrenal cortisol synthesis](https://durgical.com/en/biochemistry/pathways/adrenal-cortisol-synthesis/) ## Test yourself Think of the answer, then tap the question to see it. ## Which enzyme limits the rate of bile acid synthesis, and what represses it? CYP7A1 (cholesterol 7α-hydroxylase); bile acids returning from the gut repress it through FXR, SHP and FGF19. ## What does conjugation with glycine or taurine achieve? It lowers the pKa, so bile salts stay ionised, soluble and inside the intestinal lumen, where they emulsify fat. ## How do bile acid sequestrants lower LDL? They block reabsorption; CYP7A1 is freed from feedback, the liver uses cholesterol to make bile acids and raises its LDL receptors. ## Which bile acids are secondary, and who makes them? Deoxycholic and lithocholic acid, made by colonic bacteria from cholic and chenodeoxycholic acid. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/classic-bile-acid-synthesis-pathway/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Cerebrotendinous xanthomatosis: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/cerebrotendinous-xanthomatosis/) (MedlinePlus, US National Library of Medicine, 2026); [HSD3B7 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hsd3b7/) (MedlinePlus, US National Library of Medicine, 2026); [AKR1D1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/akr1d1/) (MedlinePlus, US National Library of Medicine, 2026); [Bile acid-CoA:amino acid N-acyltransferase (BAAT) - Homo sapiens](https://www.uniprot.org/uniprotkb/Q14032/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/classic-bile-acid-synthesis-pathway/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/classic-bile-acid-synthesis-pathway/