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DraconiticBiochemistryBiomolecules · Catabolism · Biosynthesis · MetabolismMap
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Cholesterol biosynthesis

Multistep construction of cholesterol from acetyl-derived building blocks through isoprenoid and sterol intermediates. 45 reactions, from Reactome R-HSA-191273.

  1. Squalene is oxidized to its epoxideSQNE + NADPH + H+ + O2 → SQOX + NADP+ + H2O
  2. FDPS dimer transfers IPPP to GPPGPP + IPPP → FAPP + PPi
  3. FDPS dimer transfers IPPP to DMAPPDMAPP + IPPP → GPP + PPi
  4. HMGCS1 condenses Ac-CoA and ACA-CoA to form bHMG-CoAAc-CoA + ACA-CoA + H2O → CoA-SH + bHMG-CoA + H+
  5. HMGCR dimer reduces bHMG-CoA to MVAbHMG-CoA + 2 NADPH + 2 H+ → MVA + CoA-SH + 2 NADP+
  6. Squalene 2,3-epoxide cyclizes, forming lanosterolSQOX → LAN
  7. Mevalonate is phosphorylated to mevalonate-5-phosphateMVA + ATP → MVA5P + ADP + H+
  8. Isopentenyl pyrophosphate rearranges to dimethylallyl pyrophosphateIPPP → DMAPP
  9. Reduction of presqualene diphosphate to form squalenePSQPP + H+ + NADPH → SQNE + NADP+ + PPi
  10. Two FAPP molecules dimerize to form presqualene diphosphate2 FAPP → PPi + PSQPP
  11. MVD decarboxylates MVA5PP to IPPPMVA5PP + ATP → IPPP + ADP + Pi
  12. Mevalonate-5-phosphate is further phosphorylatedMVA5P + ATP → MVA5PP + ADP
  13. Zymosterone (cholesta-8(9),24-dien-3-one) is reduced to zymosterol (cholesta-8(9),24-dien-3beta-ol)ZYMONE + NADPH + H+ → ZYMOL + NADP+
  14. 4,4-dimethylcholesta-8(9),24-dien-3beta-ol is oxidized to 4-methyl,4-carboxycholesta-8(9),24-dien-3beta-ol3 H+ + 3 NADPH + 3 O2 + 14DMLANOL → 4C4MZYMOL + 4 H2O + 3 NADP+
  15. 4-methyl,4-carboxycholesta-8(9),24-dien-3beta-ol is decarboxylated and oxidized to form 4-methylcholesta-8(9),24-dien-3-one4C4MZYMOL + NADP+ → dh4MZYMOL + H+ + CO2 + NADPH
  16. 4-methylcholesta-8(9),24-dien-3beta-ol is oxidized to 4-carboxycholesta-8(9),24-dien-3beta-ol4MZYMOL + 3 H+ + 3 NADPH + 3 O2 → 4CZYMOL + 4 H2O + 3 NADP+
  17. 4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol is reduced to 4,4-dimethylcholesta-8(9),24-dien-3beta-ol [LBR]4,4DMCHtOL + NADPH + H+ → 14DMLANOL + NADP+
  18. CYP51A1 demethylates LANLAN + 3 H+ + 3 NADPH + 3 O2 → 4,4DMCHtOL + HCOOH + 4 H2O + 3 NADP+
  19. 4-methylcholesta-8(9),24-dien-3-one is reduced to 4-methylcholesta-8(9),24-dien-3beta-oldh4MZYMOL + NADPH + H+ → 4MZYMOL + NADP+
  20. 4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol is reduced to 4,4-dimethylcholesta-8(9),24-dien-3beta-ol [TM7SF2]4,4DMCHtOL + NADPH + H+ → 14DMLANOL + NADP+
  21. 4-carboxycholesta-8(9),24-dien-3beta-ol is decarboxylated and oxidized to form cholesta-8(9),24-dien-3-one (zymosterone)4CZYMOL + NAD+ → ZYMONE + CO2 + H+ + NADH
  22. Cholesta-7,24-dien-3beta-ol is desaturated to form cholesta-5,7,24-trien-3beta-olCHdOL + NADPH + H+ + O2 → 7dhDESOL + NADP+ + 2 H2O
  23. Zymosterol is isomerized to cholesta-7,24-dien-3beta-olZYMOL → CHdOL
  24. Cholesta-5,7,24-trien-3beta-ol is reduced to desmosterol7dhDESOL + NADPH + H+ → DESMOL + NADP+
  25. Reduction of desmosterol to cholesterolDESMOL + NADPH + H+ → CHOL + NADP+
  26. ARV1 transports CHOL from ER membrane to plasma membraneCHOL → CHOL
  27. EBP isomerizes ZYMSTNL to LTHSOLZYMSTNL → LTHSOL
  28. SC5D desaturates LTHSOL to 7-dehydroCHOLLTHSOL + 2 H+ + O2 + 2 CYP450:Fe2+ → 7-dehydroCHOL + 2 H2O + 2 CYP450:Fe3+
  29. DHCR7 reduces 7-dehydroCHOL to CHOL7-dehydroCHOL + NADPH + H+ → CHOL + NADP+
  30. DHCR24 reduces ZYMOL to ZYMSTNLZYMOL + NADPH + H+ → ZYMSTNL + NADP+
  31. ACAT2 condenses 2 Ac-CoA to form ACA-CoA2 Ac-CoA → ACA-CoA + CoA-SH + H2O
  32. Phospholipid phosphatase 6 hydrolyses Presqualene diphosphate to presqualene monophosphatePSQPP + H2O → PSMP + Pi + H+
  33. HMGCR dimer binds statinsHMGCR dimer + statins → HMGCR dimer:statins
  34. GGPS1 hexamer transfers IPPP to GPPGPP + IPPP → FAPP + PPi
  35. GGPS1 hexamer transfers IPPP to DMAPPDMAPP + IPPP → GPP + PPi
  36. holo-FDPS dimer binds NBPsholo-FDPS dimer + NBPs → holo-FDPS dimer:NBPs
  37. DHCR24 reduces LAN to 24,25-dhLANLAN + NADPH + H+ → NADP+ + 24,25-dhLAN
  38. HSD17B7 reduces 4a-methyl-5a-cholest-8-en-3-one to 4a-methyl-5a-cholest-8-en-3b-ol4a-me-5a-cholest-8-en-3-one + H+ + NADPH → 4a-me-5a-cholest-8-en-3b-ol + NADP+
  39. NSDHL decarboxylates 4a-carboxy-5a-cholest-8-ene-3b-ol to 5a-cholest-8-en-3-one4a-carboxy-5a-cholest-8-en-3b-ol + NADP+ → 5a-cholest-8-en-3-one + CO2 + NADPH
  40. HSD17B7 reduces 5a-cholest-8-en-3-one to ZYMSTNL5a-cholest-8-en-3-one + H+ + NADPH → NADP+ + ZYMSTNL
  41. NSDHL decarboxylates 4a-carboxy-4b-methyl-5a-cholest-8-en-3b-ol to 4a-methyl-5a-cholest-8-en-3b-ol4a-carboxy-4b-me-5a-cholest-8-en-3b-ol + NADP+ → 4a-me-5a-cholest-8-en-3-one + CO2 + NADPH
  42. TM7SF2 reduces 4,4-diMeCholesta-8,14-dien-3-ol to 4,4-diMe5-cholest-8-en-3-ol4,4-diMe-8,14-cholestadien-3b-ol + H+ + NADPH → 4,4-diMe-5-cholest-8-en-3-ol + NADP+
  43. CYP51A1 14-demethylates 24,25-dhLAN to 4,4-diMeCholesta-8,14-dien-3-ol24,25-dhLAN + 3 CYP450:Fe2+ + 3 O2 → 4,4-diMe-8,14-cholestadien-3b-ol + HCOOH + 3 CYP450:Fe3+ + 4 H+ + 4 H2O
  44. MSMO1 oxidizes 4,4-diMe-5-cholest-8-en-3-ol to 4a-carboxy-4b-me-5a-cholest-8-en-3b-ol4,4-diMe-5-cholest-8-en-3-ol + 6 CYP450:Fe2+ + 5 H+ + 3 O2 → 4a-carboxy-4b-me-5a-cholest-8-en-3b-ol + 6 CYP450:Fe3+ + 4 H2O
  45. MSMO1 oxidizes 4a-me-5a-cholest-8-en-3b-ol to 4a-carboxy-5a-cholest-8-ene-3b-ol4a-me-5a-cholest-8-en-3b-ol + 6 CYP450:Fe2+ + 5 H+ + 3 O2 → 4a-carboxy-5a-cholest-8-en-3b-ol + 6 CYP450:Fe3+ + 4 H2O