Metabolic pathway
Cholesterol synthesis
Builds a thirty-carbon skeleton from acetyl-CoA, five carbons at a time. The atlas covers the mevalonate pathway up to lanosterol, the first sterol with rings; from there to cholesterol about twenty steps remain to be written.
- In
- 18 Acetyl-CoA + 5 Water + 14 NADPH + 14 Proton + 18 ATP + Oxygen
- Out
- Lanosterol + 18 Coenzyme A + 14 NADP+ + 18 ADP + 6 Inorganic phosphate + 6 Carbon dioxide + 6 Pyrophosphate
- Location
- Cytosol
Fun facts
- HMG-CoA reductaseIt is the target of statins. Accumulated sterols also slow it down in two ways at once: they cut its production and speed up its destruction, so the cell adjusts the amount of enzyme, not just its activity.
- Lanosterol synthaseIt is one of the most precise reactions known: of the hundreds of products that could come from folding that chain, the enzyme gets just one.
Reactions
| # | Enzyme | ΔG°′ |
|---|---|---|
| 1×6 | Cytosolic thiolaseEC 2.3.1.92 Acetyl-CoA ⇌ Acetoacetyl-CoA + Coenzyme A | — |
| 2×6 | Cytosolic HMG-CoA synthaseEC 2.3.3.10 · irreversibleAcetoacetyl-CoA + Acetyl-CoA + Water → HMG-CoA + Coenzyme A | — |
| 3×6 | HMG-CoA reductaseEC 1.1.1.34 · irreversibleHMG-CoA + 2 NADPH + 2 Proton → Mevalonate + Coenzyme A + 2 NADP+ | — |
| 4×6 | Mevalonate kinaseEC 2.7.1.36 · irreversibleMevalonate + ATP → Mevalonate 5-phosphate + ADP | — |
| 5×6 | Phosphomevalonate kinaseEC 2.7.4.2 · irreversibleMevalonate 5-phosphate + ATP → Mevalonate 5-diphosphate + ADP | — |
| 6×6 | Diphosphomevalonate decarboxylaseEC 4.1.1.33 · irreversibleMevalonate 5-diphosphate + ATP → Isopentenyl diphosphate + ADP + Inorganic phosphate + Carbon dioxide | — |
| 7×2 | Isopentenyl-diphosphate isomeraseEC 5.3.3.2Isopentenyl diphosphate ⇌ Dimethylallyl diphosphate | — |
| 8×2 | Geranyl-diphosphate synthaseEC 2.5.1.1 · irreversibleDimethylallyl diphosphate + Isopentenyl diphosphate → Geranyl diphosphate + Pyrophosphate | — |
| 9×2 | Farnesyl-diphosphate synthaseEC 2.5.1.10 · irreversibleGeranyl diphosphate + Isopentenyl diphosphate → Farnesyl diphosphate + Pyrophosphate | — |
| 10 | Squalene synthaseEC 2.5.1.21 · irreversible2 Farnesyl diphosphate + NADPH + Proton → Squalene + 2 Pyrophosphate + NADP+ | — |
| 11 | Squalene monooxygenaseEC 1.14.14.17 · irreversibleSqualene + Oxygen + NADPH + Proton → 2,3-Oxidosqualene + Water + NADP+ | — |
| 12 | Lanosterol synthaseEC 5.4.99.7 · irreversible2,3-Oxidosqualene → Lanosterol | — |
0 of 12 reactions with a documented ΔG.
Use Shift to select several
The data sheet includes the map. The logo goes at the bottom.
Sources
- Nelson, D. L. & Cox, M. M. (2021). Lehninger. Principios de bioquímica, 8.ª ed., ch. 21