ENTRY       hsa04975                    Pathway
NAME        Fat digestion and absorption - Homo sapiens (human)
DESCRIPTION Fat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, dietary TAG is hydrolyzed to fatty acids (FA) and monoacylglycerols (MAG) by pancreatic lipase. These products are then emulsified with the help of phospholipids (PL) and bile acids (BA) present in bile to form micelles. Free FAs and MAGs are taken up by the enterocyte where they are rapidly resynthesized in endoplasmic reticulum (ER) to form TAG. PLs from the diet as well as bile - mainly LPA - too are absorbed by the enterocyte and are acylated to form phosphatidic acid (PA), which is also converted into TAG. Absorbed cholesterol (CL) is acylated to cholesterol esters (CE). Within the ER, TAG joins CE and apolipoprotein B (ApoB) to form chylomicrons that enter circulation through the lymph.
CLASS       Organismal Systems; Digestive system
PATHWAY_MAP hsa04975  Fat digestion and absorption
DRUG        D01966  Ezetimibe (JAN/USP/INN)
            D04028  Orlistat (JAN/USP/INN)
            D05060  Mitratapide (USAN/INN)
            D06283  Varespladib sodium (USAN)
            D09208  Cetilistat (JAN/USAN/INN)
            D09637  Lomitapide (USAN/INN)
            D09638  Lomitapide mesylate (USAN)
            D10657  Pradigastat sodium (USAN)
            D10664  Pradigastat (USAN)
DBLINKS     GO: 0044241 0030299
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        8513  LIPF; lipase F, gastric type [KO:K14452] [EC:3.1.1.3]
            5406  PNLIP; pancreatic lipase [KO:K14073] [EC:3.1.1.3]
            5407  PNLIPRP1; pancreatic lipase related protein 1 [KO:K14074] [EC:3.1.1.3]
            5408  PNLIPRP2; pancreatic lipase related protein 2 (gene/pseudogene) [KO:K14075] [EC:3.1.1.3]
            1056  CEL; carboxyl ester lipase [KO:K12298] [EC:3.1.1.13 3.1.1.3]
            8399  PLA2G10; phospholipase A2 group X [KO:K01047] [EC:3.1.1.4]
            26279  PLA2G2D; phospholipase A2 group IID [KO:K01047] [EC:3.1.1.4]
            30814  PLA2G2E; phospholipase A2 group IIE [KO:K01047] [EC:3.1.1.4]
            50487  PLA2G3; phospholipase A2 group III [KO:K01047] [EC:3.1.1.4]
            64600  PLA2G2F; phospholipase A2 group IIF [KO:K01047] [EC:3.1.1.4]
            81579  PLA2G12A; phospholipase A2 group XIIA [KO:K01047] [EC:3.1.1.4]
            84647  PLA2G12B; phospholipase A2 group XIIB [KO:K01047] [EC:3.1.1.4]
            5319  PLA2G1B; phospholipase A2 group IB [KO:K01047] [EC:3.1.1.4]
            5322  PLA2G5; phospholipase A2 group V [KO:K01047] [EC:3.1.1.4]
            5320  PLA2G2A; phospholipase A2 group IIA [KO:K01047] [EC:3.1.1.4]
            391013  PLA2G2C; phospholipase A2 group IIC [KO:K01047] [EC:3.1.1.4]
            1208  CLPS; colipase [KO:K14460]
            948  CD36; CD36 molecule [KO:K06259]
            2806  GOT2; glutamic-oxaloacetic transaminase 2 [KO:K14455] [EC:2.6.1.1]
            2169  FABP2; fatty acid binding protein 2 [KO:K08751]
            2168  FABP1; fatty acid binding protein 1 [KO:K08750]
            376497  SLC27A1; solute carrier family 27 member 1 [KO:K08745] [EC:6.2.1.-]
            10999  SLC27A4; solute carrier family 27 member 4 [KO:K08745] [EC:6.2.1.-]
            10554  AGPAT1; 1-acylglycerol-3-phosphate O-acyltransferase 1 [KO:K13509] [EC:2.3.1.51]
            10555  AGPAT2; 1-acylglycerol-3-phosphate O-acyltransferase 2 [KO:K13509] [EC:2.3.1.51]
            8611  PLPP1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
            8613  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
            8612  PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
            80168  MOGAT2; monoacylglycerol O-acyltransferase 2 [KO:K14457] [EC:2.3.1.22]
            346606  MOGAT3; monoacylglycerol O-acyltransferase 3 [KO:K14456] [EC:2.3.1.20 2.3.1.22]
            8694  DGAT1; diacylglycerol O-acyltransferase 1 [KO:K11155] [EC:2.3.1.20 2.3.1.75 2.3.1.76]
            84649  DGAT2; diacylglycerol O-acyltransferase 2 [KO:K11160] [EC:2.3.1.20 2.3.1.75]
            949  SCARB1; scavenger receptor class B member 1 [KO:K13885]
            29881  NPC1L1; NPC1 like intracellular cholesterol transporter 1 [KO:K14461]
            39  ACAT2; acetyl-CoA acetyltransferase 2 [KO:K00626] [EC:2.3.1.9]
            38  ACAT1; acetyl-CoA acetyltransferase 1 [KO:K00626] [EC:2.3.1.9]
            64240  ABCG5; ATP binding cassette subfamily G member 5 [KO:K05683]
            64241  ABCG8; ATP binding cassette subfamily G member 8 [KO:K05684]
            337  APOA4; apolipoprotein A4 [KO:K08760]
            338  APOB; apolipoprotein B [KO:K14462]
            4547  MTTP; microsomal triglyceride transfer protein [KO:K14463]
            335  APOA1; apolipoprotein A1 [KO:K08757]
            19  ABCA1; ATP binding cassette subfamily A member 1 [KO:K05641]
COMPOUND    C00010  CoA
            C00040  Acyl-CoA
            C00162  Fatty acid
            C00165  Diacylglycerol
            C00187  Cholesterol
            C00416  Phosphatidate
            C00422  Triacylglycerol
            C00681  1-Acyl-sn-glycerol 3-phosphate
            C00865  Phospholipid
            C01558  Bile salt
            C01885  1-Acylglycerol
            C02112  2-Acylglycerol
            C02530  Cholesterol ester
REFERENCE   PMID:19158321
  AUTHORS   Iqbal J, Hussain MM
  TITLE     Intestinal lipid absorption.
  JOURNAL   Am J Physiol Endocrinol Metab 296:E1183-94 (2009)
            DOI:10.1152/ajpendo.90899.2008
REFERENCE   PMID:20522896
  AUTHORS   Goodman BE
  TITLE     Insights into digestion and absorption of major nutrients in humans.
  JOURNAL   Adv Physiol Educ 34:44-53 (2010)
            DOI:10.1152/advan.00094.2009
REFERENCE   PMID:19280719
  AUTHORS   Niot I, Poirier H, Tran TT, Besnard P
  TITLE     Intestinal absorption of long-chain fatty acids: evidence and uncertainties.
  JOURNAL   Prog Lipid Res 48:101-15 (2009)
            DOI:10.1016/j.plipres.2009.01.001
REFERENCE   PMID:15286736
  AUTHORS   Shi Y, Burn P
  TITLE     Lipid metabolic enzymes: emerging drug targets for the treatment of obesity.
  JOURNAL   Nat Rev Drug Discov 3:695-710 (2004)
            DOI:10.1038/nrd1469
REFERENCE   PMID:20148678
  AUTHORS   Mansbach CM, Siddiqi SA
  TITLE     The biogenesis of chylomicrons.
  JOURNAL   Annu Rev Physiol 72:315-33 (2010)
            DOI:10.1146/annurev-physiol-021909-135801
REFERENCE   PMID:19116371
  AUTHORS   Shi Y, Cheng D
  TITLE     Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism.
  JOURNAL   Am J Physiol Endocrinol Metab 297:E10-8 (2009)
            DOI:10.1152/ajpendo.90949.2008
REFERENCE   PMID:10924713
  AUTHORS   Ros E
  TITLE     Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk.
  JOURNAL   Atherosclerosis 151:357-79 (2000)
            DOI:10.1016/S0021-9150(00)00456-1
REFERENCE   PMID:12621063
  AUTHORS   Yen CL, Farese RV Jr
  TITLE     MGAT2, a monoacylglycerol acyltransferase expressed in the small intestine.
  JOURNAL   J Biol Chem 278:18532-7 (2003)
            DOI:10.1074/jbc.M301633200
REFERENCE   PMID:17495606
  AUTHORS   Levy E, Spahis S, Sinnett D, Peretti N, Maupas-Schwalm F, Delvin E, Lambert M, Lavoie MA
  TITLE     Intestinal cholesterol transport proteins: an update and beyond.
  JOURNAL   Curr Opin Lipidol 18:310-8 (2007)
            DOI:10.1097/MOL.0b013e32813fa2e2
REFERENCE   PMID:18830418
  AUTHORS   Williams KJ
  TITLE     Molecular processes that handle -- and mishandle -- dietary lipids.
  JOURNAL   J Clin Invest 118:3247-59 (2008)
            DOI:10.1172/JCI35206
REFERENCE   PMID:11504671
  AUTHORS   Lu K, Lee MH, Patel SB
  TITLE     Dietary cholesterol absorption; more than just bile.
  JOURNAL   Trends Endocrinol Metab 12:314-20 (2001)
            DOI:10.1016/S1043-2760(01)00433-7
REFERENCE   PMID:14976303
  AUTHORS   Klett EL, Patel SB
  TITLE     Biomedicine. Will the real cholesterol transporter please stand up.
  JOURNAL   Science 303:1149-50 (2004)
            DOI:10.1126/science.1095519
REFERENCE   PMID:17002594
  AUTHORS   Wang DQ
  TITLE     Regulation of intestinal cholesterol absorption.
  JOURNAL   Annu Rev Physiol 69:221-48 (2007)
            DOI:10.1146/annurev.physiol.69.031905.160725
REFERENCE   PMID:19663632
  AUTHORS   Patel JP, Brocks DR
  TITLE     The effect of oral lipids and circulating lipoproteins on the metabolism of drugs.
  JOURNAL   Expert Opin Drug Metab Toxicol 5:1385-98 (2009)
            DOI:10.1517/17425250903176439
REFERENCE   PMID:15891388
  AUTHORS   Hussain MM, Fatma S, Pan X, Iqbal J
  TITLE     Intestinal lipoprotein assembly.
  JOURNAL   Curr Opin Lipidol 16:281-5 (2005)
            DOI:10.1097/01.mol.0000169347.53568.5a
REFERENCE   PMID:20493784
  AUTHORS   Kindel T, Lee DM, Tso P
  TITLE     The mechanism of the formation and secretion of chylomicrons.
  JOURNAL   Atheroscler Suppl 11:11-6 (2010)
            DOI:10.1016/j.atherosclerosissup.2010.03.003
REL_PATHWAY hsa00561  Glycerolipid metabolism
            hsa04530  Tight junction
            hsa04972  Pancreatic secretion
            hsa04976  Bile secretion
KO_PATHWAY  ko04975
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