Cholesterol metabolism with Bloch and Kandutsch-Russell pathways (Mus musculus)

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444324441LXRalpha/betaSterol effluxothersSrebf19Z-palmitoleic acidNr1h3FasnCE(16:1)Soat1Acot1Block PathwayHmgcr7alpha-hydroxycholesterolAcetyl-CoAAbca1DHCR24Dhcr7Ch25hAcetoacetyl-CoAHMG-CoAMevalonic acidMevalonate-5-PMevalonate-5-PPIsopentenyl-PPDimethylallyl-PPGeranyl-PPFarnesyl-PPSqualeneSqualene-2,3-epoxideDiepoxy-squaleneLanosterol24,25-epoxycholesterol24,25-dihydrolanosterol32-hydroxylanosterol4,4-dimethylcholesta-5,8,24-trienol4,4-dimethylcholest-8-enol14-demethyl-lanosterol4-alpha-methylcholest-8-enolZymosterol4-alpha-methyl-cholest-8-enoneZymostenolLathosterol7-dehdrocholesterolCholestadienol7-dehydodesmosterolDesmosterolCholesterolSc5dEbpNsdhlCyp51Tm7fs2Msmo1Hsd17b7Dhcr247-oxocholesterolCholestenone4beta-hydroxycholesterol24S-hydroxycholesterol25-hydroxycholesterol27-hydroxycholesterolCholesteryl esters (CE)Cyp46a1Cyp27a1Acyl-CoASoat2Acot2Hmgcs1Hmgcs2MvkPmvkMvdSqleIdi1Idi2Fdft1Ggps1FdpsLssKandutsch-Russell PathwayPreSqualeneCyp51Dhcr7Dhcr24CE(18:1)Nr1h2Abcg1Mylip (IDOL)LDLR degradationSrebf2Sterol biosynthesisAcsl1Acsl3Acsl4Elovl2Elovl3Elovl4Elovl5Fads1Fads2Scd1Scd2Acot1Acot2Fatty acid biosynthesisOleic acid4-methyl zymostenol4-methyl zymostenone24-methyl-4-carboxyzymostenone2dihydro-FF-MASdihydro-T-MAS22Cyp51A12TM7SF244SC4MOL4NSDHLLBR44-methyl zymosterol4-methyl zymosterone4-methyl-4-carboxyzymosteroneFF-MAST-MASDHCR14SC4MOLNSDHLLBR4HSD17B7444SC4MOL2NSDHLHSD17B7Cyp51A14HSD17B744444


Description

This pathway is inspired by the Lipidmaps>Sterol lipids expended pathway display [1] and extended with Scheme 1 from Acimovic et al (2013).

Literature suggests that cholesterol synthesis preferentially starts with the Bloch pathway, however there is a shift to the Kandutsch-Russell part via lathosterol [Bae et al, 1997].

Dashed lines indicate that multiple steps are involved to create the final product. Several regulatory effects concerning the metabolites of cholesterol have been indicated as well. The content from the Bloch and Kandutsch-Russel pathways have been checked against literature, and discrepancies compared to the original LipidMaps pathway have been coloured turquoise.

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Ontology Terms

 

Bibliography

  1. Ačimovič J, Rozman D; ''Steroidal triterpenes of cholesterol synthesis.''; Molecules, 2013 PubMed Europe PMC Scholia
  2. Dennis EA, Deems RA, Harkewicz R, Quehenberger O, Brown HA, Milne SB, Myers DS, Glass CK, Hardiman G, Reichart D, Merrill AH Jr, Sullards MC, Wang E, Murphy RC, Raetz CR, Garrett TA, Guan Z, Ryan AC, Russell DW, McDonald JG, Thompson BM, Shaw WA, Sud M, Zhao Y, Gupta S, Maurya MR, Fahy E, Subramaniam S; ''A mouse macrophage lipidome.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  3. Bogan RL, Debarber AE, Hennebold JD; ''Liver x receptor modulation of gene expression leading to proluteolytic effects in primate luteal cells.''; Biol Reprod, 2012 PubMed Europe PMC Scholia
  4. Bae SH, Paik YK; ''Cholesterol biosynthesis from lanosterol: development of a novel assay method and characterization of rat liver microsomal lanosterol delta 24-reductase.''; Biochem J, 1997 PubMed Europe PMC Scholia
  5. Mazein A, Watterson S, Hsieh WY, Griffiths WJ, Ghazal P; ''A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.''; Biochem Pharmacol, 2013 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
125078view10:59, 20 January 2023Conroy lipidsmore ECs
125077view10:47, 20 January 2023Conroy lipidsadd EC to comments, some fixes
125035view15:08, 16 January 2023Conroy lipidsupdate CE identifier to lipidaps
124754view08:57, 8 December 2022DeSlUpdated link to LIPID MAPS PWs.
124718view10:46, 5 December 2022Conroy lipids
124717view10:43, 5 December 2022Conroy lipidsadd rhea, try to fix floating conversions
124714view10:19, 2 December 2022Conroy lipids
124713view10:18, 2 December 2022Conroy lipids
124712view09:22, 2 December 2022Conroy lipids
124711view09:19, 2 December 2022Conroy lipids
124710view09:10, 2 December 2022Conroy lipids
124709view08:51, 2 December 2022Conroy lipids
124703view09:44, 28 November 2022Conroy lipidsadd intermediates 32-oxo/hydroxy 24-25dehydrolanost.
124700view22:33, 25 November 2022Conroy lipidsmore intermediates in KR pathway
124699view19:24, 25 November 2022Conroy lipidsmore intermediates added to K-S pathway
124696view15:14, 25 November 2022Conroy lipidsadd mising intermediates to Bloch pathway
124693view15:49, 24 November 2022Conroy lipidsmore cleanup, rhea additions
124692view14:53, 24 November 2022Conroy lipidsfix missing connections
124691view14:42, 24 November 2022Conroy lipidstidy uo, remove duplication, fix IDs to lipidmaps, add some intermediates
124680view11:42, 23 November 2022Conroy lipidsadd 32-oxolanosterol step
124679view15:19, 22 November 2022EgonwMade a pathway clickable
124677view11:44, 22 November 2022Conroy lipidsmore rhea and link to vit D metabolism
124676view10:53, 22 November 2022Conroy lipidsmore rheas
124675view10:30, 22 November 2022Conroy lipidsadd more Rhea IDs, include IPP in places it was missing
124674view19:23, 21 November 2022Conroy lipidsupdate with more rhea
124672view16:17, 21 November 2022Conroy lipidsbegin swap of arrow to mim-conversion and add rhea
123453view04:57, 28 July 2022EgonwFixed the xref
123452view19:27, 27 July 2022EgonwReplaced the system codes with full names (sorry, my bad)
123385view14:57, 22 July 2022EgonwAdded identifiers for the SMILES in the comments
120298view14:30, 26 November 2021Conroy lipidsupdated DB ref to dihydro-FF-MAS, which was completely wrong
118069view10:42, 24 May 2021EweitzModified title
116238view15:09, 21 April 2021DeSlUpdated wrong UTF-8 encoding for ref
116237view15:06, 21 April 2021DeSlStarted fixing UTF-8 encoding issue for lit.ref
116236view15:02, 21 April 2021DeSlConnected last unconnected line (Cyp7a1)
116221view08:05, 21 April 2021Egonw
116220view06:53, 21 April 2021EgonwUpdated the data source of a UniProt identifier to ensure interoperability
115465view18:16, 21 February 2021Conroy lipidsadded Cyp7a1 as cholesterol to 7alpah-Chol enzyme
115420view16:52, 18 February 2021Conroy lipidsupdated Acot1/2 enzymes to Acat1/2- incorrect enzyme specfied
107591view15:11, 23 October 2019DeSlOntology Term : 'lipid signaling pathway' added !
107590view15:11, 23 October 2019DeSlOntology Term : 'cholesterol metabolic pathway' added !
107589view15:10, 23 October 2019DeSlOntology Term : 'PW:0000002' removed !
107588view15:10, 23 October 2019DeSlOntology Term : 'cholesterol biosynthetic pathway' added !
106325view08:31, 21 August 2019DeSlAdded general LipidMaps publication.
102711view11:44, 21 January 2019DeSlchanged weird symbols for lit ref
102710view11:38, 21 January 2019DeSlAnnotated prequalene (assuming this is presqualene-2P)
102709view10:58, 21 January 2019DeSlAdded title, journal and year for refs
102708view10:55, 21 January 2019DeSlRemoved weird signs in lit. ref
102707view10:54, 21 January 2019DeSlAdded lit. ref. for Kandutsch-Russell PW
102706view10:53, 21 January 2019DeSlAnnotated two more metabolites
102705view10:46, 21 January 2019DeSlAdded SMILES to comments for compounds which could not be linked to an identifier based on name; all for Kandutsch-Russell PW

External references

DataNodes

View all...
NameTypeDatabase referenceComment
14-demethyl-lanosterolMetaboliteLMST01010176 (LIPID MAPS)
24,25-dihydrolanosterolMetaboliteLMST01010087 (LIPID MAPS)
24,25-epoxycholesterolMetaboliteLMST01010012 (LIPID MAPS)
24S-hydroxycholesterolMetaboliteLMST01010019 (LIPID MAPS)
25-hydroxycholesterolMetaboliteLMST01010018 (LIPID MAPS)
27-hydroxycholesterolMetaboliteLMST01010057 (LIPID MAPS)
32-hydroxylanosterolMetaboliteLMST01010124 (LIPID MAPS)
4,4-dimethylcholest-8-enolMetaboliteLMST01010225 (LIPID MAPS)
4,4-dimethylcholesta- 5,8,24-trienolMetaboliteLMST01010149 (LIPID MAPS)
4-alpha-methyl-cholest-8-enoneMetaboliteLMST01010236 (LIPID MAPS)
4-alpha-methylcholest-8-enolMetaboliteLMST01010197 (LIPID MAPS)
4-methyl zymostenolMetabolite22212495 (PubChem-compound)
4-methyl zymostenoneMetabolite
4-methyl zymosterolMetabolite
4-methyl zymosteroneMetabolite
4-methyl-4-carboxy zymostenoneMetabolite
4-methyl-4-carboxy zymosteroneMetabolite
4beta-hydroxycholesterolMetaboliteLMST01010014 (LIPID MAPS)
7-dehdrocholesterolMetaboliteLMST01010069 (LIPID MAPS)
7-dehydodesmosterolMetaboliteLMST01010121 (LIPID MAPS)
7-oxocholesterolMetaboliteLMST01010049 (LIPID MAPS)
7alpha-hydroxycholesterolMetaboliteLMST01010013 (LIPID MAPS)
9Z-palmitoleic acidMetabolite
Abca1Protein
Abcg1Protein
Acetoacetyl-CoAMetaboliteLMFA07050030 (LIPID MAPS)
Acetyl-CoAMetaboliteLMFA07050281 (LIPID MAPS)
Acot1Protein
Acot1GeneProduct26897 (Entrez Gene)
Acot2Protein
Acot2GeneProduct171210 (Entrez Gene)
Acsl1Protein
Acsl3Protein
Acsl4Protein
Acyl-CoAMetaboliteLMFA07050000 (LIPID MAPS)
Block PathwayPathway
CE(16:1)Metabolite
CE(18:1)Metabolite
Ch25hGeneProduct12642 (Entrez Gene)
CholestadienolMetaboliteLMST01010206 (LIPID MAPS)
CholestenoneMetaboliteLMST01010015 (LIPID MAPS)
CholesterolMetaboliteLMST01010001 (LIPID MAPS)
Cholesteryl esters (CE)Metabolite
Cyp27a1GeneProduct104086 (Entrez Gene)
Cyp46a1GeneProduct13116 (Entrez Gene)
Cyp51GeneProduct13121 (Entrez Gene)
Cyp51A1ProteinQ8K0C4 (Uniprot-TrEMBL)
DHCR14Protein
DHCR24ProteinQ8VCH6 (Uniprot-TrEMBL)
DesmosterolMetaboliteLMST01010016 (LIPID MAPS)
Dhcr24GeneProduct74754 (Entrez Gene)
Dhcr7GeneProduct13360 (Entrez Gene)
Diepoxy-squaleneMetaboliteLMPR01060038 (LIPID MAPS)
Dimethylallyl-PPMetaboliteLMPR01010001 (LIPID MAPS)
EbpGeneProduct13595 (Entrez Gene)
Elovl2Protein
Elovl3Protein
Elovl4Protein
Elovl5Protein
FF-MASMetaboliteaka 14-demethyl-14-dehydrolanosterol
Fads1Protein
Fads2Protein
Farnesyl-PPMetaboliteLMPR0103010002 (LIPID MAPS)
FasnProtein
Fdft1GeneProduct14137 (Entrez Gene)
FdpsGeneProduct110196 (Entrez Gene)
Geranyl-PPMetaboliteLMPR0102010001 (LIPID MAPS)
Ggps1GeneProduct14593 (Entrez Gene)
HMG-CoAMetaboliteLMFA07050116 (LIPID MAPS)
HSD17B7Protein
HmgcrGeneProduct15357 (Entrez Gene)
Hmgcs1GeneProduct208715 (Entrez Gene)
Hmgcs2GeneProduct15360 (Entrez Gene)
Hsd17b7GeneProduct15490 (Entrez Gene)
Idi1GeneProduct319554 (Entrez Gene)
Idi2GeneProduct320581 (Entrez Gene)
Isopentenyl-PPMetaboliteLMPR01010008 (LIPID MAPS)
Kandutsch-

Russell

Pathway		Pathway
LBRProteinQ3U9G9 (Uniprot-TrEMBL)
LanosterolMetaboliteLMST01010017 (LIPID MAPS)
LathosterolMetaboliteLMST01010089 (LIPID MAPS)
LssGeneProduct16987 (Entrez Gene)
Mevalonate-5-PMetaboliteLMFA01050415 (LIPID MAPS)
Mevalonate-5-PPMetaboliteLMFA01050416 (LIPID MAPS)
Mevalonic acidMetaboliteLMFA01050352 (LIPID MAPS)
Msmo1GeneProduct66234 (Entrez Gene) aka Sc4mol
MvdGeneProduct192156 (Entrez Gene)
MvkGeneProduct17855 (Entrez Gene)
Mylip (IDOL)Protein
NSDHLProteinQ9R1J0 (Uniprot-TrEMBL)
Nr1h2Protein
Nr1h3Protein
NsdhlGeneProduct18194 (Entrez Gene)
Oleic acidMetabolite
PmvkGeneProduct68603 (Entrez Gene)
PreSqualeneMetabolite
SC4MOLProteinQ9CRA4 (Uniprot-TrEMBL)
Sc5dGeneProduct235293 (Entrez Gene)
Scd1Protein
Scd2Protein
Soat1GeneProduct20652 (Entrez Gene)
Soat2GeneProduct223920 (Entrez Gene)
SqleGeneProduct20775 (Entrez Gene)
Squalene-2,3-epoxideMetaboliteLMPR0106010010 (LIPID MAPS)
SqualeneMetaboliteLMPR0106010002 (LIPID MAPS)
Srebf1Protein
Srebf2Protein
T-MASMetabolite
TM7SF2ProteinQ71KT5 (Uniprot-TrEMBL)
Tm7fs2GeneProduct73166 (Entrez Gene)
ZymostenolMetaboliteLMST01010096 (LIPID MAPS)
ZymosterolMetaboliteLMST01010066 (LIPID MAPS)
dihydro-FF-MASMetabolite
dihydro-T-MASMetabolite

Annotated Interactions

No annotated interactions

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