KEGG   PATHWAY: hsa04979
Entry
hsa04979                    Pathway                                
Name
Cholesterol metabolism - Homo sapiens (human)
Description
Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids, vitamin D and steroid hormones. Cholesterol homeostasis in humans is regulated by well-balanced mechanisms of intestinal uptake, endogenous synthesis, transport in lipoprotein particles, and biliary excretion. Its abnormal metabolism can lead to increased risk for various endocrine disorders and cardiovascular diseases.
Class
Organismal Systems; Digestive system
Pathway map
hsa04979  Cholesterol metabolism
hsa04979

Network
  Element
N00332  Vesicular uptake of lipoproteins
N00336  PCSK9-mediated LDLR degradation
Drug
D01202  Melinamide (JAN)
D02047  Dextran sulfate sodium (JAN)
D03012  Avasimibe (USAN/INN)
D03343  Dextran sulfate sodium sulfur 5 (JP18)
D03447  Cetaben sodium (USAN)
D03734  Eldacimibe (USAN/INN)
D03735  Lecimibide (USAN)
D03747  Ibrolipim (USAN/INN)
D04268  Elastase ES
D05255  Omega-3-acid ethyl esters (USP)
D06195  Torcetrapib (USAN/INN)
D10335  Alirocumab (USAN)
D10377  Sebelipase alfa (USAN)
D10557  Evolocumab (USAN/INN)
D10621  Bococizumab (USAN/INN)
D11398  Frovocimab (USAN/INN)
D11648  Volanesorsen (USAN/INN)
D11650  Volanesorsen sodium (USAN)
D11753  Evinacumab (USAN/INN)
D11931  Inclisiran (USAN/INN)
D12293  Inclisiran sodium (JAN)
D12460  Muvalaplin (USAN)
D12580  Sudotaxel zendusortide (USAN/INN)
D12581  Zendusortide (USAN/INN)
D12900  Obicetrapib (USAN/INN)
D12901  Obicetrapib calcium (USAN)
Other DBs
GO: 0008203
Organism
Homo sapiens (human) [GN:hsa]
Gene
19  ABCA1; ATP binding cassette subfamily A member 1 [KO:K05641]
335  APOA1; apolipoprotein A1 [KO:K08757]
4023  LPL; lipoprotein lipase [KO:K01059] [EC:3.1.1.34]
3931  LCAT; lecithin-cholesterol acyltransferase [KO:K00650] [EC:2.3.1.43]
9388  LIPG; lipase G, endothelial type [KO:K22284] [EC:3.1.1.3]
5360  PLTP; phospholipid transfer protein [KO:K08761]
1071  CETP; cholesteryl ester transfer protein [KO:K16835]
3990  LIPC; lipase C, hepatic type [KO:K22283] [EC:3.1.1.3]
4018  LPA; lipoprotein(a) [KO:K09644] [EC:3.4.21.-]
948  CD36; CD36 molecule (CD36 blood group) [KO:K06259]
3949  LDLR; low density lipoprotein receptor [KO:K12473]
57552  NCEH1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
8435  SOAT2; sterol O-acyltransferase 2 [KO:K00637] [EC:2.3.1.26]
6646  SOAT1; sterol O-acyltransferase 1 [KO:K00637] [EC:2.3.1.26]
341  APOC1; apolipoprotein C1 [KO:K22286]
344  APOC2; apolipoprotein C2 [KO:K22287]
350  APOH; apolipoprotein H [KO:K17305]
27329  ANGPTL3; angiopoietin like 3 [KO:K22288]
51129  ANGPTL4; angiopoietin like 4 [KO:K08767]
55908  ANGPTL8; angiopoietin like 8 [KO:K22289]
949  SCARB1; scavenger receptor class B member 1 [KO:K13885]
6272  SORT1; sortilin 1 [KO:K12388]
338  APOB; apolipoprotein B [KO:K14462]
255738  PCSK9; proprotein convertase subtilisin/kexin type 9 [KO:K13050] [EC:3.4.21.-]
26119  LDLRAP1; low density lipoprotein receptor adaptor protein 1 [KO:K12474]
29116  MYLIP; myosin regulatory light chain interacting protein [KO:K10637] [EC:2.3.2.27]
348  APOE; apolipoprotein E [KO:K04524]
4035  LRP1; LDL receptor related protein 1 [KO:K04550]
4036  LRP2; LDL receptor related protein 2 [KO:K06233]
4043  LRPAP1; LDL receptor related protein associated protein 1 [KO:K22290]
3988  LIPA; lipase A, lysosomal acid type [KO:K01052] [EC:3.1.1.13]
10948  STARD3; StAR related lipid transfer domain containing 3 [KO:K22291]
7416  VDAC1; voltage dependent anion channel 1 [KO:K05862]
7417  VDAC2; voltage dependent anion channel 2 [KO:K15040]
7419  VDAC3; voltage dependent anion channel 3 [KO:K15041]
706  TSPO; translocator protein [KO:K05770]
1593  CYP27A1; cytochrome P450 family 27 subfamily A member 1 [KO:K00488] [EC:1.14.15.15]
9218  VAPA; VAMP associated protein A [KO:K06096]
9217  VAPB; VAMP associated protein B and C [KO:K10707]
4864  NPC1; NPC intracellular cholesterol transporter 1 [KO:K12385]
114879  OSBPL5; oxysterol binding protein like 5 [KO:K20464]
10577  NPC2; NPC intracellular cholesterol transporter 2 [KO:K13443]
6770  STAR; steroidogenic acute regulatory protein [KO:K16931]
27141  CIDEB; cell death inducing DFFA like effector b [KO:K25914]
1581  CYP7A1; cytochrome P450 family 7 subfamily A member 1 [KO:K00489] [EC:1.14.14.23]
8647  ABCB11; ATP binding cassette subfamily B member 11 [KO:K05664]
64240  ABCG5; ATP binding cassette subfamily G member 5 [KO:K05683]
64241  ABCG8; ATP binding cassette subfamily G member 8 [KO:K05684]
336  APOA2; apolipoprotein A2 [KO:K08758]
345  APOC3; apolipoprotein C3 [KO:K08759]
337  APOA4; apolipoprotein A4 [KO:K08760]
Compound
C00162  Fatty acid
C00187  Cholesterol
C00422  Triacylglycerol
C00865  Phospholipid
C01921  Glycocholate
C02530  Cholesterol ester
C05122  Taurocholate
C05465  Taurochenodeoxycholate
C05466  Glycochenodeoxycholate
C15610  Cholest-5-ene-3beta,26-diol
Reference
PMID:28577571
  Authors
Paththinige CS, Sirisena ND, Dissanayake V
  Title
Genetic determinants of inherited susceptibility to hypercholesterolemia - a comprehensive literature review.
  Journal
Lipids Health Dis 16:103 (2017)
DOI:10.1186/s12944-017-0488-4
Reference
PMID:24385507
  Authors
Oldoni F, Sinke RJ, Kuivenhoven JA
  Title
Mendelian disorders of high-density lipoprotein metabolism.
  Journal
Circ Res 114:124-42 (2014)
DOI:10.1161/CIRCRESAHA.113.300634
Reference
PMID:15451808
  Authors
Lusis AJ, Fogelman AM, Fonarow GC
  Title
Genetic basis of atherosclerosis: part I: new genes and pathways.
  Journal
Circulation 110:1868-73 (2004)
DOI:10.1161/01.CIR.0000143041.58692.CC
Reference
PMID:18079757
  Authors
Wasan KM, Brocks DR, Lee SD, Sachs-Barrable K, Thornton SJ
  Title
Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs: implications for drug discovery.
  Journal
Nat Rev Drug Discov 7:84-99 (2008)
DOI:10.1038/nrd2353
Reference
PMID:18216769
  Authors
Ikonen E
  Title
Cellular cholesterol trafficking and compartmentalization.
  Journal
Nat Rev Mol Cell Biol 9:125-38 (2008)
DOI:10.1038/nrm2336
Reference
PMID:26568191
  Authors
Vaziri ND
  Title
HDL abnormalities in nephrotic syndrome and chronic kidney disease.
  Journal
Nat Rev Nephrol 12:37-47 (2016)
DOI:10.1038/nrneph.2015.180
Reference
PMID:24854407
  Authors
Kingwell BA, Chapman MJ, Kontush A, Miller NE
  Title
HDL-targeted therapies: progress, failures and future.
  Journal
Nat Rev Drug Discov 13:445-64 (2014)
DOI:10.1038/nrd4279
Reference
PMID:25172365
  Authors
Do RQ, Nicholls SJ, Schwartz GG
  Title
Evolving targets for lipid-modifying therapy.
  Journal
EMBO Mol Med 6:1215-30 (2014)
DOI:10.15252/emmm.201404000
Reference
PMID:26247089
  Authors
Feingold KR, Grunfeld C
  Title
Introduction to Lipids and Lipoproteins
  Journal
Endotext (2000)
Reference
PMID:25551803
  Authors
Sacks FM
  Title
The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia.
  Journal
Curr Opin Lipidol 26:56-63 (2015)
DOI:10.1097/MOL.0000000000000146
Reference
PMID:20962428
  Authors
Yasuda T, Ishida T, Rader DJ
  Title
Update on the role of endothelial lipase in high-density lipoprotein metabolism, reverse cholesterol transport, and atherosclerosis.
  Journal
Circ J 74:2263-70 (2010)
DOI:10.1253/circj.CJ-10-0934
Reference
PMID:25359426
  Authors
Wang S, Smith JD
  Title
ABCA1 and nascent HDL biogenesis.
  Journal
Biofactors 40:547-54 (2014)
DOI:10.1002/biof.1187
Reference
PMID:28971105
  Authors
Hassan M
  Title
ANGPLT3: A novel modulator of lipid metabolism.
  Journal
Glob Cardiol Sci Pract 2017:e201706 (2017)
DOI:10.21542/gcsp.2017.6
Reference
PMID:24397894
  Authors
Dijk W, Kersten S
  Title
Regulation of lipoprotein lipase by Angptl4.
  Journal
Trends Endocrinol Metab 25:146-55 (2014)
DOI:10.1016/j.tem.2013.12.005
Reference
PMID:11254896
  Authors
Huuskonen J, Olkkonen VM, Jauhiainen M, Ehnholm C
  Title
The impact of phospholipid transfer protein (PLTP) on HDL metabolism.
  Journal
Atherosclerosis 155:269-81 (2001)
DOI:10.1016/S0021-9150(01)00447-6
Reference
PMID:22661899
  Authors
Shinkai H
  Title
Cholesteryl ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases.
  Journal
Vasc Health Risk Manag 8:323-31 (2012)
DOI:10.2147/VHRM.S25238
Reference
PMID:26435212
  Authors
Norata GD, Tsimikas S, Pirillo A, Catapano AL
  Title
Apolipoprotein C-III: From Pathophysiology to Pharmacology.
  Journal
Trends Pharmacol Sci 36:675-87 (2015)
DOI:10.1016/j.tips.2015.07.001
Reference
PMID:27312323
  Authors
Zhong LY, Cayabyab FS, Tang CK, Zheng XL, Peng TH, Lv YC
  Title
Sortilin: A novel regulator in lipid metabolism and atherogenesis.
  Journal
Clin Chim Acta 460:11-7 (2016)
DOI:10.1016/j.cca.2016.06.013
Reference
PMID:22510808
  Authors
Sorrentino V, Zelcer N
  Title
Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor.
  Journal
Curr Opin Lipidol 23:213-9 (2012)
DOI:10.1097/MOL.0b013e3283532947
Reference
PMID:25003069
  Authors
Jiang W, Song BL
  Title
Ubiquitin ligases in cholesterol metabolism.
  Journal
Diabetes Metab J 38:171-80 (2014)
DOI:10.4093/dmj.2014.38.3.171
Reference
PMID:22811413
  Authors
Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK
  Title
The PCSK9 decade.
  Journal
J Lipid Res 53:2515-24 (2012)
DOI:10.1194/jlr.R026658
Reference
PMID:26015858
  Authors
Graham A, Allen AM
  Title
Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses.
  Journal
World J Cardiol 7:277-86 (2015)
DOI:10.4330/wjc.v7.i5.277
Reference
PMID:27565112
  Authors
Elustondo P, Martin LA, Karten B
  Title
Mitochondrial cholesterol import.
  Journal
Biochim Biophys Acta 1862:90-101 (2017)
DOI:10.1016/j.bbalip.2016.08.012
Reference
PMID:26041457
  Authors
Raiborg C, Wenzel EM, Stenmark H
  Title
ER-endosome contact sites: molecular compositions and functions.
  Journal
EMBO J 34:1848-58 (2015)
DOI:10.15252/embj.201591481
Reference
PMID:24554437
  Authors
van der Kant R, Neefjes J
  Title
Small regulators, major consequences - Ca(2)(+) and cholesterol at the endosome-ER interface.
  Journal
J Cell Sci 127:929-38 (2014)
DOI:10.1242/jcs.137539
Reference
PMID:20816088
  Authors
Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, Jansen P, Heeren J, Willnow TE, Nykjaer A
  Title
Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export.
  Journal
Cell Metab 12:213-23 (2010)
DOI:10.1016/j.cmet.2010.08.006
Related
pathway
hsa00100  Steroid biosynthesis
hsa00120  Primary bile acid biosynthesis
hsa00900  Terpenoid backbone biosynthesis
hsa04975  Fat digestion and absorption
hsa04976  Bile secretion
KO pathway
ko04979   
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