Cholesterol metabolism with Bloch and Kandutsch-Russell pathways (WP4346)

This pathway is inspired by the Lipidmaps>Sterol lipids expended pathway display [https://lipidmaps.org/resources/pathways/vanted.php] and extended with Scheme 1 from Acimovic et al (2013 [https://www.ncbi.nlm.nih.gov/pubmed/23558541]). 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[https://www.ncbi.nlm.nih.gov/pubmed/9291139]). 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.
last edited

Authors

Eoinfahy, Ryanmiller, DeSl, Egonw, Conroy lipids, and Eweitz

Cited In

Organism

Mus musculus

Communities

Lipids and LIPID MAPS

Annotations

Pathway Ontology: cholesterol metabolic pathway lipid signaling pathway cholesterol biosynthetic pathway

Participants

Label Type Compact Identifier
9Z-palmitoleic acid Metabolite pubchem.compound:445638
Srebf1 GeneProduct ensembl:ENSMUSG00000020538
7alpha-hydroxycholesterol Metabolite lipidmaps:LMST01010013
Acat1 GeneProduct uniprot:Q8QZT1
Abca1 GeneProduct ensembl:ENSMUSG00000015243
Bloch Pathway Pathway None
Acetyl-CoA Metabolite lipidmaps:LMFA07050281
Ch25h GeneProduct ncbigene:12642
Hmgcr GeneProduct ncbigene:15357
Cyp7a1 GeneProduct uniprot:Q64505
Nr1h3 GeneProduct ensembl:ENSMUSG00000002108
Soat1 GeneProduct ncbigene:20652
Fasn GeneProduct ensembl:ENSMUSG00000025153
CE(16:1) Metabolite wikidata:Q412366
Dhcr7 GeneProduct ncbigene:13360
DHCR24 Protein uniprot:Q8VCH6
Acetoacetyl-CoA Metabolite lipidmaps:LMFA07050030
HMG-CoA Metabolite lipidmaps:LMFA07050116
Mevalonic acid Metabolite lipidmaps:LMFA01050352
Mevalonate-5-P Metabolite lipidmaps:LMFA01050415
Mevalonate-5-PP Metabolite lipidmaps:LMFA01050416
Isopentenyl-PP Metabolite lipidmaps:LMPR01010008
Dimethylallyl-PP Metabolite lipidmaps:LMPR01010001
Geranyl-PP Metabolite lipidmaps:LMPR0102010001
Farnesyl-PP Metabolite lipidmaps:LMPR0103010002
Squalene Metabolite lipidmaps:LMPR0106010002
Squalene-2,3-epoxide Metabolite lipidmaps:LMPR0106010010
Diepoxy-squalene Metabolite lipidmaps:LMPR0106010038
Lanosterol Metabolite lipidmaps:LMST01010017
24,25-epoxycholesterol Metabolite lipidmaps:LMST01010012
24,25-dihydrolanosterol Metabolite lipidmaps:LMST01010087
32-hydroxylanosterol Metabolite lipidmaps:LMST01010124
4,4-dimethylcholesta-5,8,24-trienol Metabolite lipidmaps:LMST01010149
4,4-dimethylcholest-8-enol Metabolite lipidmaps:LMST01010225
14-demethyl-lanosterol Metabolite lipidmaps:LMST01010176
4-alpha-methylcholest-8-enol Metabolite lipidmaps:LMST01010197
Zymosterol Metabolite lipidmaps:LMST01010066
4-alpha-methyl-cholest-8-enone Metabolite lipidmaps:LMST01010236
Zymostenol Metabolite lipidmaps:LMST01010096
Lathosterol Metabolite lipidmaps:LMST01010089
7-dehdrocholesterol Metabolite lipidmaps:LMST01010069
Cholestadienol Metabolite lipidmaps:LMST01010206
7-dehydodesmosterol Metabolite lipidmaps:LMST01010121
Desmosterol Metabolite lipidmaps:LMST01010016
Cholesterol Metabolite lipidmaps:LMST01010001
Sc5d GeneProduct ncbigene:235293
Ebp GeneProduct ncbigene:13595
Nsdhl GeneProduct ncbigene:18194
Cyp51 GeneProduct ncbigene:13121
Tm7fs2 GeneProduct ncbigene:73166
Msmo1 GeneProduct ncbigene:66234
Hsd17b7 GeneProduct ncbigene:15490
Dhcr24 GeneProduct ncbigene:74754
7-oxocholesterol Metabolite lipidmaps:LMST01010049
Cholestenone Metabolite lipidmaps:LMST01010015
4beta-hydroxycholesterol Metabolite lipidmaps:LMST01010014
24S-hydroxycholesterol Metabolite lipidmaps:LMST01010019
25-hydroxycholesterol Metabolite lipidmaps:LMST01010018
27-hydroxycholesterol Metabolite lipidmaps:LMST01010057
Cholesteryl esters (CE) Metabolite chebi:17002
Cyp46a1 GeneProduct ncbigene:13116
Cyp27a1 GeneProduct ncbigene:104086
Acyl-CoA Metabolite lipidmaps:LMFA07050000
Soat2 GeneProduct ncbigene:223920
Acat2 GeneProduct uniprot:Q8CAY6
Hmgcs1 GeneProduct ncbigene:208715
Hmgcs2 GeneProduct ncbigene:15360
Mvk GeneProduct ncbigene:17855
Pmvk GeneProduct ncbigene:68603
Mvd GeneProduct ncbigene:192156
Sqle GeneProduct ncbigene:20775
Idi1 GeneProduct ncbigene:319554
Idi2 GeneProduct ncbigene:320581
Fdft1 GeneProduct ncbigene:14137
Ggps1 GeneProduct ncbigene:14593
Fdps GeneProduct ncbigene:110196
Lss GeneProduct ncbigene:16987
Kandutsch-Russell Pathway Pathway None
PreSqualene Metabolite wikidata:Q27088444
Cyp51 GeneProduct ncbigene:13121
Dhcr7 GeneProduct ncbigene:13360
Dhcr24 GeneProduct ncbigene:74754
CE(18:1) Metabolite wikidata:Q27116670
Nr1h2 GeneProduct ensembl:ENSMUSG00000060601
Abcg1 GeneProduct ensembl:ENSMUSG00000024030
Mylip (IDOL) GeneProduct ensembl:ENSMUSG00000038175
Srebf2 GeneProduct ensembl:ENSMUSG00000022463
Acsl1 GeneProduct ensembl:ENSMUSG00000018796
Acsl3 GeneProduct ensembl:ENSMUSG00000032883
Acsl4 GeneProduct ensembl:ENSMUSG00000031278
Elovl2 Protein ensembl:ENSMUSG00000021364
Elovl3 Protein ensembl:ENSMUSG00000038754
Elovl4 Protein ensembl:ENSMUSG00000032262
Elovl5 Protein ensembl:ENSMUSG00000032349
Fads1 Protein ensembl:ENSMUSG00000010663
Fads2 Protein ensembl:ENSMUSG00000024665
Scd1 Protein ensembl:ENSMUSG00000037071
Scd2 Protein uniprot:P13011
Acot1 GeneProduct ensembl:ENSMUSG00000072949
Acot2 GeneProduct ensembl:ENSMUSG00000021226
Fatty acid biosynthesis Pathway wikipathways:WP4491
Oleic acid Metabolite wikidata:Q207688
4-methyl zymostenol Metabolite pubchem.compound:22212495
4-methyl zymostenone Metabolite LIPID MAPS
4-methyl-4-carboxyzymostenone Metabolite LIPID MAPS
dihydro-FF-MAS Metabolite lipidmaps:LMST01010277
dihydro-T-MAS Metabolite LIPID MAPS
Cyp51A1 Protein uniprot:Q8K0C4
TM7SF2 Protein uniprot:Q71KT5
SC4MOL Protein uniprot:Q9CRA4
NSDHL Protein uniprot:Q9R1J0
LBR Protein uniprot:Q3U9G9
4-methyl zymosterol Metabolite PubChem-compound
4-methyl zymosterone Metabolite LIPID MAPS
4-methyl-4-carboxyzymosterone Metabolite LIPID MAPS
FF-MAS Metabolite cas:64284-64-6
T-MAS Metabolite LIPID MAPS
DHCR14 aka Tm7fs2 Protein ncbigene:73166
SC4MOL Protein uniprot:Q9CRA4
NSDHL Protein uniprot:Q9R1J0
LBR Protein uniprot:Q3U9G9
HSD17B7 Protein ncbigene:15490
SC4MOL Protein uniprot:Q9CRA4
NSDHL Protein uniprot:Q9R1J0
HSD17B7 Protein ncbigene:15490
Cyp51A1 Protein uniprot:Q8K0C4
HSD17B7 Protein ncbigene:15490

References

  1. 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 Sep 1;326 ( Pt 2)(Pt 2):609–16. PubMed Europe PMC Scholia
  2. Dennis EA, Deems RA, Harkewicz R, Quehenberger O, Brown HA, Milne SB, et al. A mouse macrophage lipidome. J Biol Chem. 2010 Dec 17;285(51):39976–85. 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 Mar 30;86(3):89. PubMed Europe PMC Scholia
  4. Ačimovič J, Rozman D. Steroidal triterpenes of cholesterol synthesis. Molecules. 2013 Apr 4;18(4):4002–17. PubMed Europe PMC Scholia