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Bile acid synthesis !

The liver turns cholesterol into bile acids, which help digest fat and are the body's main way out for cholesterol.

Updated 2026-11-01

Key facts

  • The rate-limiting step is cholesterol 7α-hydroxylase (CYP7A1), slowed by bile acids returning to the liver.
  • Primary (liver): cholic and chenodeoxycholic. Secondary (colonic bacteria): deoxycholic and lithocholic.
  • They are conjugated with glycine or taurine (bile salts), stored in the gallbladder and reabsorbed in the terminal ileum: enterohepatic circulation.
  • Only a small fraction (about 5%) is lost in faeces and replaced by new synthesis.

In detail

  • Classic route: CYP7A1 adds a 7α-OH to cholesterol; the nucleus is then modified (CYP8B1 adds cholic acid's 12α-OH).
  • The side chain is oxidised and shortened (CYP27A1 and peroxisomal β-oxidation): from 27 to 24 carbons.
  • Alternative route: starts with mitochondrial CYP27A1 and makes mainly chenodeoxycholic acid.
  • The liver conjugates them with glycine or taurine, so they are ionised in the gut as bile salts.
  • In the gut they form micelles with fats, cholesterol and fat-soluble vitamins.
  • In the colon bacteria deconjugate them and remove the 7α-OH: secondary bile acids form.
  • In the terminal ileum (ASBT transporter) most are reabsorbed and return via the portal vein; FXR and FGF19 then slow CYP7A1.

Clinical notes

  • If bile holds more cholesterol than bile salts and phospholipids, cholesterol stones form.
  • Bile acid sequestrants lower LDL by forcing the liver to use up cholesterol.
  • CYP27A1 deficiency causes cerebrotendinous xanthomatosis: tendon xanthomas, cataracts and neurological damage.
  • Cholestasis retains bile salts: itching and jaundice.

Pathways

Test yourself

Think of the answer, then tap the question to see it.

Which enzyme limits bile acid synthesis?

Cholesterol 7α-hydroxylase (CYP7A1).

Where are bile salts reabsorbed?

In the terminal ileum, through the ASBT transporter.

What separates a primary from a secondary bile acid?

The liver makes primary ones from cholesterol; secondary ones form when colonic bacteria modify a primary one.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Synthesis of bile acids and bile salts (R-HSA-192105) (Reactome, 2026); Cerebrotendinous xanthomatosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.