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

From WikiPathways

Revision as of 11:44, 21 January 2019 by DeSl (Talk | contribs)
Jump to: navigation, search
44342, 5444441othersSterol effluxLXRalpha/betaNr1h3Abca1CE(16:1)FasnCh25hAcetyl-CoADhcr7HmgcrSrebf1DHCR249Z-palmitoleic acid7alpha-hydroxycholesterolSoat1Acot1Bloch PathwayAcetoacetyl-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 zymostenone4-methyl-4-carboxyzymostenone33dihydro-FF-MASdihydro-T-MAS33Cyp51A13TM7SF24SC4MOL44NSDHLLBR44-methyl zymosterol4-methyl zymosterone4-methyl-4-carboxyzymosteroneFF-MAST-MASDHCR14 aka Tm7fs2SC4MOLNSDHLLBR44HSD17B744SC4MOL3NSDHLHSD17B7Cyp51A14HSD17B7444444444444444


Description

This pathway is inspired by the Lipidmaps>Sterol lipids expended pathway display [1] and extended with Scheme 1 from Acimovic et al (2013 [2]).

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[3]).

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 differences compared to the original LipidMaps pathway have been coloured turquoise.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Ačimovič J, Rozman D; ''Steroidal triterpenes of cholesterol synthesis.''; Molecules, 2013 PubMed Europe PMC
  2. Bae SH, Paik YK; ''''; , PubMed Europe PMC
  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
  4. Ačimovič J, Rozman D; ''Steroidal triterpenes of cholesterol synthesis.''; Molecules, 2013
  5. Ačimovič J, Rozman D; ''Steroidal triterpenes of cholesterol synthesis.''; Molecules, 2013 PubMed Europe PMC
  6. 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

History

View all...
CompareRevisionActionTimeUserComment
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
102704view09:56, 21 January 2019DeSlModified description
102703view09:54, 21 January 2019DeSlAdded SMILES to comments for compounds which could not be linked to an identifier based on name; annotated one metabolite with CAS; all for Bloch PW
102702view09:28, 21 January 2019DeSlAnnotated two more missing proteins
102701view09:22, 21 January 2019DeSlAnnotated bottom right part
102681view12:33, 18 January 2019DeSlAdded more IDs for proteins of fatty acid synthesis
102519view08:44, 3 January 2019EgonwFixed the identifier for Diepoxy-squalene (ID scheme change or typo?)
98941view13:06, 16 October 2018DeSlFixed lit. refs.
98769view14:40, 5 October 2018DeSlConnected DHCR24 to last conversion from Bloch to KR PW
98768view14:35, 5 October 2018DeSlAdded more info from lit. ref
98752view15:31, 4 October 2018DeSlModified description
98751view15:24, 4 October 2018DeSlConnected unconnected lines
98668view15:43, 27 September 2018DeSlModified description
98667view15:42, 27 September 2018DeSlModified description
98666view15:42, 27 September 2018DeSlModified description
98665view15:37, 27 September 2018DeSlAdded last enzymes needed for conversions.
98664view15:25, 27 September 2018DeSlAdded more info from lit. ref (on bloch PW).
98657view09:01, 27 September 2018DeSlAdded more info from lit. ref (more detailed steps)
98654view15:54, 26 September 2018DeSlAdded more info from lit ref, changed colour for clarity.
98653view15:51, 26 September 2018DeSlAdded info from lit. ref.
98652view15:39, 26 September 2018DeSlAdded last part of missing signalling track
98651view15:23, 26 September 2018DeSlAdded more details on signalling function of metabolites.
98640view15:38, 24 September 2018DeSlAdded some missing nodes
98639view15:35, 24 September 2018DeSlConnected groups of enzymes correclty, changed layout.
98638view14:24, 24 September 2018DeSlModified title
98637view14:21, 24 September 2018DeSlModified title
98610view12:42, 21 September 2018RyanmillerOntology Term : 'classic metabolic pathway' added !
98576view15:53, 17 September 2018EoinfahyNew pathway

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 zymostenoneMetaboliteC12CC[C@@]3([H])C(C)[C](=O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/CC(\C)/C)CC[C]21H
4-methyl zymosterolMetaboliteC12CC[C@@]3([H])C(C)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/C=C(\C)/C)CC[C]21H
4-methyl zymosteroneMetaboliteC12CC[C@@]3([H])C(C)[C](=O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/C=C(\C)/C)CC[C]21H
4-methyl-4-carboxy zymostenoneMetaboliteC12CC[C@@]3([H])C(C)(COOH)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/CC(\C)/C)CC[C]21H
4-methyl-4-carboxy zymosteroneMetaboliteC12CC[C@@]3([H])C(C)(COOH)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/C=C(\C)/C)CC[C]21H
4beta-hydroxycholesterolMetaboliteLMST01010014 (LIPID MAPS)
7-dehdrocholesterolMetaboliteLMST01010069 (LIPID MAPS)
7-dehydodesmosterolMetaboliteLMST01010121 (LIPID MAPS)
7-oxocholesterolMetaboliteLMST01010049 (LIPID MAPS)
7alpha-hydroxycholesterolMetaboliteLMST01010013 (LIPID MAPS)
9Z-palmitoleic acidMetabolite445638 (PubChem-compound) Assuming this is omega 7-type
Abca1GeneProductENSMUSG00000015243 (Ensembl)
Abcg1GeneProductENSMUSG00000024030 (Ensembl)
Acetoacetyl-CoAMetaboliteLMFA07050030 (LIPID MAPS)
Acetyl-CoAMetaboliteLMFA07050281 (LIPID MAPS)
Acot1GeneProduct26897 (Entrez Gene)
Acot1GeneProductENSMUSG00000072949 (Ensembl)
Acot2GeneProduct171210 (Entrez Gene)
Acot2GeneProductENSMUSG00000021226 (Ensembl)
Acsl1GeneProductENSMUSG00000018796 (Ensembl)
Acsl3GeneProductENSMUSG00000032883 (Ensembl)
Acsl4GeneProductENSMUSG00000031278 (Ensembl)
Acyl-CoAMetaboliteLMFA07050000 (LIPID MAPS)
Bloch PathwayPathway
CE(16:1)MetaboliteQ412366 (Wikidata) Assuming this is omega-7 type
CE(18:1)MetaboliteQ27116670 (Wikidata) Assuming this is omega-7 type
Ch25hGeneProduct12642 (Entrez Gene)
CholestadienolMetaboliteLMST01010206 (LIPID MAPS) aka 24-dehydrolathosterol
CholestenoneMetaboliteLMST01010015 (LIPID MAPS)
CholesterolMetaboliteLMST01010001 (LIPID MAPS)
Cholesteryl esters (CE)MetaboliteCHEBI:17002 (ChEBI)
Cyp27a1GeneProduct104086 (Entrez Gene)
Cyp46a1GeneProduct13116 (Entrez Gene)
Cyp51GeneProduct13121 (Entrez Gene)
Cyp51A1ProteinQ8K0C4 (Uniprot-TrEMBL)
DHCR14 aka Tm7fs2Protein73166 (Entrez Gene)
DHCR24ProteinQ8VCH6 (Uniprot-TrEMBL)
DesmosterolMetaboliteLMST01010016 (LIPID MAPS)
Dhcr24GeneProduct74754 (Entrez Gene)
Dhcr7GeneProduct13360 (Entrez Gene)
Diepoxy-squaleneMetaboliteLMPR0106010038 (LIPID MAPS)
Dimethylallyl-PPMetaboliteLMPR01010001 (LIPID MAPS)
EbpGeneProduct13595 (Entrez Gene)
Elovl2ProteinENSMUSG00000021364 (Ensembl)
Elovl3ProteinENSMUSG00000038754 (Ensembl)
Elovl4ProteinENSMUSG00000032262 (Ensembl)
Elovl5ProteinENSMUSG00000032349 (Ensembl)
FF-MASMetabolite64284-64-6 (CAS)
  • aka 14-demethyl-14-dehydrolanosterol
  • C12CC[C@@]3([H])C(C)(C)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/C=C(\C)/C)CC=[C@@]21C SMILES
Fads1ProteinENSMUSG00000010663 (Ensembl)
Fads2ProteinENSMUSG00000024665 (Ensembl)
Farnesyl-PPMetaboliteLMPR0103010002 (LIPID MAPS)
FasnGeneProductENSMUSG00000025153 (Ensembl)
Fatty acid biosynthesisPathwayWP4491 (WikiPathways)
Fdft1GeneProduct14137 (Entrez Gene)
FdpsGeneProduct110196 (Entrez Gene)
Geranyl-PPMetaboliteLMPR0102010001 (LIPID MAPS)
Ggps1GeneProduct14593 (Entrez Gene)
HMG-CoAMetaboliteLMFA07050116 (LIPID MAPS)
HSD17B7Protein15490 (Entrez Gene)
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)GeneProductENSMUSG00000038175 (Ensembl)
NSDHLProteinQ9R1J0 (Uniprot-TrEMBL)
Nr1h2GeneProductENSMUSG00000060601 (Ensembl)
Nr1h3GeneProductENSMUSG00000002108 (Ensembl)
NsdhlGeneProduct18194 (Entrez Gene)
Oleic acidMetaboliteQ207688 (Wikidata) Aka C18:1 (omega 9)
PmvkGeneProduct68603 (Entrez Gene)
PreSqualeneMetaboliteQ27088444 (Wikidata) Annotated while assuming this compound is actually presqualene-diphosphate
SC4MOLProteinQ9CRA4 (Uniprot-TrEMBL)
Sc5dGeneProduct235293 (Entrez Gene)
Scd1ProteinENSMUSG00000037071 (Ensembl)
Scd2ProteinP13011 (Uniprot-TrEMBL)
Soat1GeneProduct20652 (Entrez Gene)
Soat2GeneProduct223920 (Entrez Gene)
SqleGeneProduct20775 (Entrez Gene)
Squalene-2,3-epoxideMetaboliteLMPR0106010010 (LIPID MAPS)
SqualeneMetaboliteLMPR0106010002 (LIPID MAPS)
Srebf1GeneProductENSMUSG00000020538 (Ensembl)
Srebf2GeneProductENSMUSG00000022463 (Ensembl)
T-MASMetaboliteC12CC[C@@]3([H])C(C)(C)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/C=C(\C)/C)CC[C]21H SMILES
TM7SF2ProteinQ71KT5 (Uniprot-TrEMBL)
Tm7fs2GeneProduct73166 (Entrez Gene)
ZymostenolMetaboliteLMST01010096 (LIPID MAPS)
ZymosterolMetaboliteLMST01010066 (LIPID MAPS)
dihydro-FF-MASMetaboliteC12CC[C@@]3([H])C(C)(C)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/CC(\C)/C)CC=[C@@]21C
dihydro-T-MASMetaboliteC12CC[C@@]3([H])C(C)(C)[C@@H](O)CC[C@]3(C)C=1CC[C@]1(C)[C@@]([H])([C@@](C)([H])CC/CC(\C)/C)CC[C]21H

Annotated Interactions

No annotated interactions

Personal tools