Cholesterol biosynthesis (Homo sapiens)

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5, 9, 12, 14, 243213, 266417, 29, 3125211820, 272311191617, 29, 3148, 3015, 22281283, 10723212nuclear envelopeendoplasmic reticulum membranecytosolH+NADP+LBRNADP+H+TM7SF2H2OCO2H+ADPNSDHLDimethylallyl pyrophosphateMevalonateH2OADPNADP+OrthophosphateHMGCR dimerNADPHNADPHNADP+ATPCO2NADP+presqualene diphosphateFormateH+NADPHpyrophosphateATPdesmosterollanosterolMVK dimerOxygenH2O4-carboxycholesta-8(9),24-dien-3beta-olCholesterolprenyltransferaseSC5DNADPHLSSH+4-methyl,4-carboxycholesta-8(9),24-dien-3beta-olNADP+Mevalonate-5-pyrophosphateHMGCS1NADP+NADPH4-methylcholesta-8(9),24-dien-3-oneNADPH4,4-dimethylcholesta-8(9),24-dien-3beta-olH+DHCR24Acetyl-CoANADPHNADHSqualene 2,3 epoxideNADP+Mevalonate-5-phosphateDHCR7H+NADPHH+OxygenHSD17B7NADPHADPpyrophosphateNADPHNADP+delta3-isopentenyl pyrophosphateNADP+ATPNADPHMVD dimerH2OFDFT (Mg2+ cofactor)cholesta-7,24-dien-3beta-olNAD+CoA-SHH+cholesta-5,7,24-trien-3beta-olNADP+NADP+OxygenH+CYP51A1H+NADHNADP+CO2acetoacetyl-CoAFarnesyl pyrophosphateSQLE:FADEBPNAD+OxygenNADPHH2Obeta-hydroxy-beta-methylglutaryl-CoApyrophosphateOxygenGeranyl pyrophosphateH+NADPHIDI1 or 2SC4MOLcholesta-8(9),24-dien-3-one4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol4-methylcholesta-8(9),24-dien-3beta-olPMVKH+H+zymosterolH+4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol4,4-dimethylcholesta-8(9),24-dien-3beta-olSqualeneH2O


Description

Cholesterol is synthesized de novo from from acetyl CoA. The overall synthetic process is outlined in the figure below. Enzymes whose regulation plays a major role in determining the rate of cholesterol synthesis in the body are highlighted in red, and connections to other metabolic processes are indicated. The transformation of lanosterol into cholesterol requires multiple steps, including the removal of three methyl groups, the reduction of one double bond and the migration of another. These reactions may not occur in a single fixed order in the body, so the linear pathway laid out here following the work of Gaylor and colleagues (Gaylor 2002) is an oversimplification of the process that occurs in vivo. Defects in several of the enzymes involved in this process are associated with human disease and have provided useful insights into the regulatory roles of cholesterol and its synthetic intermediates in human development (Herman 2003; Song et al. 2005).

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Bibliography

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History

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114644view16:11, 25 January 2021ReactomeTeamReactome version 75
113092view11:15, 2 November 2020ReactomeTeamReactome version 74
112326view15:24, 9 October 2020ReactomeTeamReactome version 73
101225view11:12, 1 November 2018ReactomeTeamreactome version 66
100763view20:37, 31 October 2018ReactomeTeamreactome version 65
100307view19:14, 31 October 2018ReactomeTeamreactome version 64
99853view15:58, 31 October 2018ReactomeTeamreactome version 63
99410view14:35, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99098view12:39, 31 October 2018ReactomeTeamreactome version 62
93876view13:42, 16 August 2017ReactomeTeamreactome version 61
93443view11:23, 9 August 2017ReactomeTeamreactome version 61
86534view09:20, 11 July 2016ReactomeTeamreactome version 56
83203view10:22, 18 November 2015ReactomeTeamVersion54
81583view13:07, 21 August 2015ReactomeTeamVersion53
77044view08:34, 17 July 2014ReactomeTeamFixed remaining interactions
76749view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76074view10:13, 11 June 2014ReactomeTeamRe-fixing comment source
75784view11:31, 10 June 2014ReactomeTeamReactome 48 Update
75134view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74781view08:52, 30 April 2014ReactomeTeamReactome46
72909view15:13, 14 December 2013EgonwArgh...
72907view15:11, 14 December 2013EgonwFixed the Uniprot-TrEMBL data sources.
72904view15:07, 14 December 2013Egonw
72903view15:06, 14 December 2013EgonwUpdated the UniProt data source with UniProt/TrEMBL.
68898view17:29, 8 July 2013MaintBotUpdated to 2013 gpml schema
44990view14:36, 6 October 2011MartijnVanIerselOntology Term : 'cholesterol biosynthetic pathway' added !
42157view23:24, 4 March 2011MaintBotModified categories
42018view21:50, 4 March 2011MaintBotAutomatic update
39821view05:51, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
4,4-

dimethylcholesta-8 (9),14,24-trien- 3beta-ol

MetaboliteREACT_10169 (Reactome)
4,4-

dimethylcholesta-8 (9),14,24-trien- 3beta-ol

MetaboliteREACT_10253 (Reactome)
4,4-dimethylcholesta-8

(9),24-dien-3beta-ol

MetaboliteREACT_10787 (Reactome)
4,4-dimethylcholesta-8

(9),24-dien-3beta-ol

MetaboliteREACT_10958 (Reactome)
4-

carboxycholesta-8 (9),24-dien- 3beta-ol

MetaboliteREACT_10167 (Reactome)
4-methyl,4-

carboxycholesta-8(9), 24-dien-3beta-ol

MetaboliteREACT_10298 (Reactome)
4-methylcholesta-8

(9),24-dien-3-one

MetaboliteREACT_10464 (Reactome)
4-methylcholesta-8

(9),24-dien-3beta-ol

MetaboliteREACT_10930 (Reactome)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Acetyl-CoA Metabolite15351 (ChEBI)
CO2 Metabolite16526 (ChEBI)
CYP51A1 ProteinQ16850 (Uniprot-TrEMBL)
Cholesterol Metabolite16113 (ChEBI)
CoA-SH Metabolite15346 (ChEBI)
DHCR24 ProteinQ15392 (Uniprot-TrEMBL)
DHCR7 ProteinQ9UBM7 (Uniprot-TrEMBL)
Dimethylallyl

pyrophosphate

Metabolite16057 (ChEBI)
EBP ProteinQ15125 (Uniprot-TrEMBL)
FDFT (Mg2+

cofactor)

ComplexREACT_9885 (Reactome)
Farnesyl

pyrophosphate

Metabolite17407 (ChEBI)
Formate Metabolite30751 (ChEBI)
Geranyl

pyrophosphate

Metabolite17211 (ChEBI)
H+ Metabolite15378 (ChEBI)
H2O Metabolite15377 (ChEBI)
HMGCR

dimer

ComplexREACT_9875 (Reactome)
HMGCS1 ProteinQ01581 (Uniprot-TrEMBL)
HSD17B7 ProteinREACT_10277 (Reactome)
IDI1 or 2 ComplexREACT_9627 (Reactome)
LBR ProteinQ14739 (Uniprot-TrEMBL)
LSS ProteinP48449 (Uniprot-TrEMBL)
MVD dimer ComplexREACT_9808 (Reactome)
MVK dimer ComplexREACT_9683 (Reactome)
Mevalonate Metabolite17710 (ChEBI)
Mevalonate-5-

phosphate

Metabolite17436 (ChEBI)
Mevalonate-5-

pyrophosphate

Metabolite15899 (ChEBI)
NAD+ Metabolite15846 (ChEBI)
NADH Metabolite16908 (ChEBI)
NADP+ Metabolite18009 (ChEBI)
NADPH Metabolite16474 (ChEBI)
NSDHL ProteinQ15738 (Uniprot-TrEMBL)
Orthophosphate Metabolite18367 (ChEBI)
Oxygen Metabolite15379 (ChEBI)
PMVK ProteinQ15126 (Uniprot-TrEMBL)
SC4MOL ProteinQ15800 (Uniprot-TrEMBL)
SC5D ProteinO75845 (Uniprot-TrEMBL)
SQLE:FAD ComplexREACT_9686 (Reactome)
Squalene Metabolite15440 (ChEBI)
Squalene 2,3

epoxide

Metabolite15441 (ChEBI)
TM7SF2 ProteinO76062 (Uniprot-TrEMBL)
acetoacetyl-CoA Metabolite15345 (ChEBI)
beta-hydroxy-beta-

methylglutaryl-CoA

Metabolite15467 (ChEBI)
cholesta-5,7,24-

trien-3beta-ol

Metabolite27910 (ChEBI)
cholesta-7,24-

dien-3beta-ol

Metabolite16290 (ChEBI)
cholesta-8(9),24-

dien-3-one

MetaboliteREACT_10977 (Reactome)
delta3-isopentenyl

pyrophosphate

Metabolite16584 (ChEBI)
desmosterol Metabolite17737 (ChEBI)
lanosterol Metabolite16521 (ChEBI)
prenyltransferase REACT_26922 (Reactome)
presqualene

diphosphate

Metabolite15442 (ChEBI)
pyrophos

phate

Metabolite29888 (ChEBI)
pyrophosp

hate

Metabolite29888 (ChEBI)
zymosterol Metabolite18252 (ChEBI)

Annotated Interactions

No annotated interactions

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