KEGG   PATHWAY: hsa04975Help
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
BRITE hierarchy
Pathway map
hsa04975  Fat digestion and absorption
hsa04975

Ortholog table
Disease
H00845  Familial amyloidosis
H00930  Hypoalphalipoproteinemia
H01108  CD36 deficiency
H01213  Gallbladder disease
H01270  Familial hypobetalipoproteinemia (FHBL)
Drug
D01966  Ezetimibe (JAN/USAN/INN)
D04028  Orlistat (JAN/USAN/INN)
D06283  Varespladib sodium (USAN)
D08107  Varespladib (USAN/INN)
D08221  Varespladib methyl (USAN)
D09637  Lomitapide (USAN/INN)
D09638  Lomitapide mesylate (USAN)
D10657  Pradigastat sodium (USAN)
D10664  Pradigastat (USAN)
Other DBs
BSID: 194385
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:3.1.1.3 3.1.1.13]
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]
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:2.3.1.22 2.3.1.20]
8694  DGAT1; diacylglycerol O-acyltransferase 1 [KO:K11155] [EC:2.3.1.76 2.3.1.75 2.3.1.20]
84649  DGAT2; diacylglycerol O-acyltransferase 2 [KO:K11160] [EC:2.3.1.75 2.3.1.20]
949  SCARB1; scavenger receptor class B member 1 [KO:K13885]
29881  NPC1L1; NPC1 like intracellular cholesterol transporter 1 [KO:K14461]
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]
10999  SLC27A4; solute carrier family 27 member 4 [KO:K08745] [EC:6.2.1.-]
39  ACAT2; acetyl-CoA acetyltransferase 2 [KO:K00626] [EC:2.3.1.9]
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Hussain MM, Fatma S, Pan X, Iqbal J
  Title
Intestinal lipoprotein assembly.
  Journal
Curr Opin Lipidol 16:281-5 (2005)
Reference
  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
KO pathway
ko04975   

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