From the five-carbon units of the mevalonate pathway to squalene, lanosterol and cholesterol
Route: Dimethylallyl diphosphate + Isopentenyl diphosphate → Farnesyl diphosphate → Squalene → (S)-2,3-Epoxysqualene → Lanosterol → 4,4-Dimethyl-5α-cholesta-8,14,24-trien-3β-ol → Cholesterol
Farnesyl pyrophosphate synthase joins one dimethylallyl diphosphate to one isopentenyl diphosphate, which gives the ten-carbon geranyl diphosphate, and then adds a second isopentenyl diphosphate to make the fifteen-carbon farnesyl diphosphate. One enzyme does both condensations. Squalene synthase, an enzyme of the endoplasmic reticulum, joins two farnesyl diphosphate molecules tail to tail with NADPH as the reducing agent and releases the thirty-carbon squalene. Squalene monooxygenase uses O₂ and NADPH to make squalene epoxide. Lanosterol synthase protonates the epoxide and the chain folds into four rings in one reaction, which forms four new carbon-carbon bonds and six new chiral centers. The last stage, from lanosterol to cholesterol, removes three methyl groups, reduces one double bond and moves another, and takes 19 steps with 9 different enzymes. Those steps are collapsed here. In the order shown, the first of them is sterol 14α-demethylase, which removes the 14α-methyl group in three steps, each with O₂ and NADPH, and releases it as formate; the product is shown. The arrow after it stands for the remaining steps, and the structure on that arrow is the isomerase EBP, which catalyzes one of them by moving a double bond. Cells also use other orders. In the Kandutsch-Russell order, the double bond in the side chain is reduced first.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Farnesyl pyrophosphate synthase | 2.5.1.10 | PPᵢ, PPᵢ | |
| 2 | Squalene synthase | 2.5.1.21 | NADPH | NADP⁺, PPᵢ, PPᵢ |
| 3 | Squalene monooxygenase (squalene epoxidase) | 1.14.14.17 | O₂, NADPH | NADP⁺, H₂O |
| 4 | Lanosterol synthase (oxidosqualene cyclase) | 5.4.99.7 | ||
| 5 | Sterol 14α-demethylase (CYP51A1) | 1.14.14.154 | O₂, O₂, O₂, NADPH, NADPH, NADPH | NADP⁺, NADP⁺, NADP⁺, H₂O, H₂O, H₂O, H₂O, Formate |
| 6 | 3β-Hydroxysteroid Δ8,Δ7-isomerase (EBP) | 5.3.3.5 |
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).