| Entry |
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| Name |
Fat digestion and absorption - Homo sapiens (human)
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| 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.
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| Class |
Organismal Systems; Digestive system
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| Pathway map |
| Fat digestion and absorption |

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| Disease |
| Familial amyloidosis | | Hypoalphalipoproteinemia | | CD36 deficiency | | Gallbladder disease | | Familial hypobetalipoproteinemia (FHBL) |
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| Drug |
| Ezetimibe (JAN/USAN/INN) | | Orlistat (USAN/INN) | | Varespladib sodium (USAN) | | Varespladib (USAN/INN) | | Varespladib methyl (USAN) | | Lomitapide (USAN/INN) | | Lomitapide mesylate (USAN) |
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| Other DBs |
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| Organism |
Homo sapiens (human) [GN: hsa]
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| Gene |
| | | | | PNLIPRP1; pancreatic lipase-related protein 1 [KO: K14074] [EC: 3.1.1.3] | | PNLIPRP2; pancreatic lipase-related protein 2 [KO: K14075] [EC: 3.1.1.3] | | | | | | | | | | | | | | | | | | PLA2G1B; phospholipase A2, group IB (pancreas) [KO: K01047] [EC: 3.1.1.4] | | | | PLA2G2A; phospholipase A2, group IIA (platelets, synovial fluid) [KO: K01047] [EC: 3.1.1.4] | | | | CLPS; colipase, pancreatic [KO: K14460] | | CD36; CD36 molecule (thrombospondin receptor) [KO: K06259] | | GOT2; glutamic-oxaloacetic transaminase 2, mitochondrial (aspartate aminotransferase 2) [KO: K14455] [EC: 2.6.1.1] | | FABP2; fatty acid binding protein 2, intestinal [KO: K08751] | | FABP1; fatty acid binding protein 1, liver [KO: K08750] | | AGPAT1; 1-acylglycerol-3-phosphate O-acyltransferase 1 [KO: K13509] [EC: 2.3.1.51] | | AGPAT2; 1-acylglycerol-3-phosphate O-acyltransferase 2 [KO: K13509] [EC: 2.3.1.51] | | PPAP2A; phosphatidic acid phosphatase type 2A [KO: K01080] [EC: 3.1.3.4] | | PPAP2B; phosphatidic acid phosphatase type 2B [KO: K01080] [EC: 3.1.3.4] | | PPAP2C; phosphatidic acid phosphatase type 2C [KO: K01080] [EC: 3.1.3.4] | | MOGAT2; monoacylglycerol O-acyltransferase 2 [KO: K14457] [EC: 2.3.1.22] | | | | | | | | SCARB1; scavenger receptor class B, member 1 [KO: K13885] | | NPC1L1; NPC1-like 1 [KO: K14461] | | ABCG5; ATP-binding cassette, sub-family G (WHITE), member 5 [KO: K05683] | | ABCG8; ATP-binding cassette, sub-family G (WHITE), member 8 [KO: K05684] | | APOA4; apolipoprotein A-IV [KO: K08760] | | APOB; apolipoprotein B (including Ag(x) antigen) [KO: K14462] | | MTTP; microsomal triglyceride transfer protein [KO: K14463] | | APOA1; apolipoprotein A-I [KO: K08757] | | ABCA1; ATP-binding cassette, sub-family A (ABC1), member 1 [KO: K05641] | | SLC27A4; solute carrier family 27 (fatty acid transporter), member 4 [KO: K08745] [EC:6.2.1.-] | | |
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| Compound |
| CoA | | Acyl-CoA | | Fatty acid | | Diacylglycerol | | Cholesterol | | Phosphatidate | | Triacylglycerol | | 1-Acyl-sn-glycerol 3-phosphate | | Phospholipid | | Bile salt | | 1-Acylglycerol | | Cholesterol ester |
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| Reference |
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| Authors |
Iqbal J, Hussain MM |
| Title |
Intestinal lipid absorption. |
| Journal |
Am J Physiol Endocrinol Metab 296:E1183-94 (2009) |
| Reference |
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| Authors |
Goodman BE |
| Title |
Insights into digestion and absorption of major nutrients in humans. |
| Journal |
Adv Physiol Educ 34:44-53 (2010) |
| Reference |
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| 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) |
| Reference |
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| 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) |
| Reference |
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| Authors |
Mansbach CM, Siddiqi SA |
| Title |
The biogenesis of chylomicrons. |
| Journal |
Annu Rev Physiol 72:315-33 (2010) |
| Reference |
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| 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) |
| Reference |
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| Authors |
Ros E |
| Title |
Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk. |
| Journal |
Atherosclerosis 151:357-79 (2000) |
| Reference |
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| Authors |
Yen CL, Farese RV Jr |
| Title |
MGAT2, a monoacylglycerol acyltransferase expressed in the small intestine. |
| Journal |
J Biol Chem 278:18532-7 (2003) |
| Reference |
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| 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) |
| Reference |
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| Authors |
Williams KJ |
| Title |
Molecular processes that handle -- and mishandle -- dietary lipids. |
| Journal |
J Clin Invest 118:3247-59 (2008) |
| Reference |
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| Authors |
Lu K, Lee MH, Patel SB |
| Title |
Dietary cholesterol absorption; more than just bile. |
| Journal |
Trends Endocrinol Metab 12:314-20 (2001) |
| Reference |
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| Authors |
Klett EL, Patel SB |
| Title |
Biomedicine. Will the real cholesterol transporter please stand up. |
| Journal |
Science 303:1149-50 (2004) |
| Reference |
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| Authors |
Wang DQ |
| Title |
Regulation of intestinal cholesterol absorption. |
| Journal |
Annu Rev Physiol 69:221-48 (2007) |
| Reference |
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| 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) |
| Reference |
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| Authors |
Hussain MM, Fatma S, Pan X, Iqbal J |
| Title |
Intestinal lipoprotein assembly. |
| Journal |
Curr Opin Lipidol 16:281-5 (2005) |
| Reference |
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| Authors |
Kindel T, Lee DM, Tso P |
| Title |
The mechanism of the formation and secretion of chylomicrons. |
| Journal |
Atheroscler Suppl 11:11-6 (2010) |
| KO pathway |
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