Cholesterol to cholic acid in the liver, and its joining to glycine or taurine
Route: Cholesterol → 7α-Hydroxycholesterol → 7α-Hydroxycholest-4-en-3-one → 7α,12α-Dihydroxycholest-4-en-3-one → 7α,12α-Dihydroxy-5β-cholestan-3-one → 5β-Cholestane-3α,7α,12α-triol → Cholic acid → Glycocholic acid + Taurocholic acid
Bile salts are made from cholesterol in the liver, stored in the gallbladder and released into the small intestine, where they help dissolve dietary lipids. They are also the main breakdown products of cholesterol. This is the classic pathway. An alternative (acidic) pathway that starts with CYP27A1 is not shown. Cholesterol 7α-monooxygenase adds a hydroxyl group at carbon 7 using O₂ and NADPH, and this step limits the rate of bile acid synthesis. HSD3B7 then uses NAD⁺ to oxidize the 3-hydroxyl group to a ketone and moves the double bond from carbons 5 and 6 to carbons 4 and 5. The 12α-hydroxylase CYP8B1 adds a hydroxyl group at carbon 12. This enzyme sets the ratio of cholic acid to chenodeoxycholic acid, so the route shown, with the 12α-hydroxyl group, leads to cholic acid. AKR1D1 uses NADPH to reduce the carbon-carbon double bond, which gives the 5β configuration. AKR1C4 then uses NADPH to reduce the 3-ketone to a 3α-hydroxyl group; related enzymes may also do this. CYP27A1 then oxidizes the end of the side chain in three steps to a carboxylic acid, and later steps in the peroxisome shorten the side chain by three carbons. Those steps are collapsed into one arrow and give cholic acid, a 24-carbon acid. Cholic acid is joined to glycine, or to taurine, by an amide bond. The enzyme BAAT does this with choloyl-CoA, the CoA thioester of cholic acid, and the products are glycocholic acid and taurocholic acid. Cholic acid that returns from the intestine is first made into the CoA thioester again, which costs one ATP (it becomes AMP and PPᵢ). In the cell these are the bile salts glycocholate and taurocholate. Steps with no structure in the figure are marked by the enzyme name on the arrow. The route to chenodeoxycholic acid is not shown.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Cholesterol 7α-monooxygenase (CYP7A1) | 1.14.14.23 | O₂, NADPH | NADP⁺, H₂O |
| 2 | HSD3B7 (no structure shown) | NAD⁺ | NADH | |
| 3 | 7α-Hydroxycholest-4-en-3-one 12α-hydroxylase (CYP8B1) | 1.14.14.139 | O₂, NADPH | NADP⁺, H₂O |
| 4 | Δ4-3-Oxosteroid 5β-reductase (AKR1D1) | 1.3.1.3 | NADPH | NADP⁺ |
| 5 | 3α-Hydroxysteroid dehydrogenase (AKR1C4) | 1.1.1.50 | NADPH | NADP⁺ |
| 6 | CYP27A1 and the steps that shorten the side chain (collapsed) | |||
| 7 | BAAT, with the choloyl-CoA made by the side-chain steps (no structure shown) | Glycine, Taurine | CoA-SH |
Build any of these from its atoms.
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).