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
NETWORK     nt06320  APOB-LDLR signaling
  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)
            D10557  Evolocumab (USAN/INN)
            D10621  Bococizumab (USAN/INN)
            D11398  Frovocimab (USAN)
            D11648  Volanesorsen (USAN/INN)
            D11650  Volanesorsen sodium (USAN)
            D11753  Evinacumab (USAN/INN)
            D11931  Inclisiran (USAN/INN)
            D12293  Inclisiran sodium (JAN)
            D12460  Muvalaplin (USAN)
DBLINKS     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 [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
REL_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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