ENTRY       hsa04973                    Pathway
NAME        Carbohydrate digestion and absorption - Homo sapiens (human)
DESCRIPTION Dietary carbohydrate in humans and omnivorous animals is a major nutrient. The carbohydrates that we ingest vary from the lactose in milk to complex carbohydrates. These carbohydrates are digested to monosaccharides, mostly glucose, galactose and fructose, prior to absorption in the small intestine. Glucose and galactose are initially transported into the enterocyte by SGLT1 located in the apical brush border membrane and then exit through the basolateral membrane by either GLUT2 or exocytosis. In a new model of intestinal glucose absorption, transport by SGLT1 induces rapid insertion and activation of GLUT2 in the brush border membrane by a PKC betaII-dependent mechanism. Moreover, trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/alpha-gustducin to activate PLC-beta2 and PKC-beta II. Fructose is transported separately by the brush border GLUT5 and then released out of the enterocyte into the blood by GLUT2.
CLASS       Organismal Systems; Digestive system
PATHWAY_MAP hsa04973  Carbohydrate digestion and absorption
DRUG        D00216  Acarbose (JAN/USAN/INN)
            D00625  Miglitol (JP18/USAN/INN)
            D01665  Voglibose (JP18/USAN/INN)
            D02381  Aspartame (NF/INN)
            D08836  Acesulfame potassium (NF)
            D08862  Aspartame acesulfame (NF)
            D09779  Emiglitate (JAN/INN)
            D10669  Sotagliflozin (USAN/INN)
DBLINKS     GO: 0044245 0001951
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        278  AMY1C; amylase alpha 1C [KO:K01176] [EC:3.2.1.1]
            279  AMY2A; amylase alpha 2A [KO:K01176] [EC:3.2.1.1]
            276  AMY1A; amylase alpha 1A [KO:K01176] [EC:3.2.1.1]
            280  AMY2B; amylase alpha 2B [KO:K01176] [EC:3.2.1.1]
            277  AMY1B; amylase alpha 1B [KO:K01176] [EC:3.2.1.1]
            3938  LCT; lactase [KO:K01229] [EC:3.2.1.108 3.2.1.62]
            8972  MGAM; maltase-glucoamylase [KO:K12047] [EC:3.2.1.20 3.2.1.3]
            93432  MGAM2; maltase-glucoamylase 2 (putative) [KO:K12047] [EC:3.2.1.20 3.2.1.3]
            6476  SI; sucrase-isomaltase [KO:K01203] [EC:3.2.1.48 3.2.1.10]
            6523  SLC5A1; solute carrier family 5 member 1 [KO:K14158]
            476  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
            477  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
            478  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
            480  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:7.2.2.13]
            23439  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
            481  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
            482  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
            483  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
            486  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
            6514  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
            3101  HK3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
            3098  HK1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
            3099  HK2; hexokinase 2 [KO:K00844] [EC:2.7.1.1]
            80201  HKDC1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
            2542  SLC37A4; solute carrier family 37 member 4 [KO:K08171]
            2538  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
            57818  G6PC2; glucose-6-phosphatase catalytic subunit 2 [KO:K01084] [EC:3.1.3.9]
            92579  G6PC3; glucose-6-phosphatase catalytic subunit 3 [KO:K01084] [EC:3.1.3.9]
            6518  SLC2A5; solute carrier family 2 member 5 [KO:K08143]
            5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
            5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
            8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
            5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
            5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
            5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
            207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
            208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
            10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
            776  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
            5579  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
            80834  TAS1R2; taste 1 receptor member 2 [KO:K04625]
            83756  TAS1R3; taste 1 receptor member 3 [KO:K04626]
            346562  GNAT3; G protein subunit alpha transducin 3 [KO:K19729]
            23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
            5330  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
            5331  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
            5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
COMPOUND    C00011  CO2
            C00031  D-Glucose
            C00033  Acetate
            C00076  Calcium cation
            C00089  Sucrose
            C00092  D-Glucose 6-phosphate
            C00095  D-Fructose
            C00124  D-Galactose
            C00163  Propanoate
            C00165  Diacylglycerol
            C00208  Maltose
            C00238  Potassium cation
            C00243  Lactose
            C00246  Butanoic acid
            C00282  Hydrogen
            C00369  Starch
            C00707  Xylan
            C00714  Pectin
            C00760  Cellulose
            C01330  Sodium cation
            C01355  Fructan
            C01835  Maltotriose
            C02049  Limit dextrin
            C05981  Phosphatidylinositol-3,4,5-trisphosphate
            C08822  Gum arabic
            C12284  Saccharin sodium anhydrous
            C12285  Sucralose
REFERENCE   PMID:16586532
  AUTHORS   Drozdowski LA, Thomson AB
  TITLE     Intestinal sugar transport.
  JOURNAL   World J Gastroenterol 12:1657-70 (2006)
            DOI:10.3748/wjg.v12.i11.1657
REFERENCE   PMID:14642859
  AUTHORS   Wright EM, Martin MG, Turk E
  TITLE     Intestinal absorption in health and disease--sugars.
  JOURNAL   Best Pract Res Clin Gastroenterol 17:943-56 (2003)
            DOI:10.1016/S1521-6918(03)00107-0
REFERENCE   PMID:18393659
  AUTHORS   Kellett GL, Brot-Laroche E, Mace OJ, Leturque A
  TITLE     Sugar absorption in the intestine: the role of GLUT2.
  JOURNAL   Annu Rev Nutr 28:35-54 (2008)
            DOI:10.1146/annurev.nutr.28.061807.155518
REFERENCE   PMID:19001049
  AUTHORS   Mace OJ, Lister N, Morgan E, Shepherd E, Affleck J, Helliwell P, Bronk JR, Kellett GL, Meredith D, Boyd R, Pieri M, Bailey PD, Pettcrew R, Foley D
  TITLE     An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine.
  JOURNAL   J Physiol 587:195-210 (2009)
            DOI:10.1113/jphysiol.2008.159616
REFERENCE   PMID:16186415
  AUTHORS   Kellett GL, Brot-Laroche E
  TITLE     Apical GLUT2: a major pathway of intestinal sugar absorption.
  JOURNAL   Diabetes 54:3056-62 (2005)
            DOI:10.2337/diabetes.54.10.3056
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:17222166
  AUTHORS   Wright EM, Hirayama BA, Loo DF
  TITLE     Active sugar transport in health and disease.
  JOURNAL   J Intern Med 261:32-43 (2007)
            DOI:10.1111/j.1365-2796.2006.01746.x
REFERENCE   PMID:12512027
  AUTHORS   Santer R, Hillebrand G, Steinmann B, Schaub J
  TITLE     Intestinal glucose transport: evidence for a membrane traffic-based pathway in humans.
  JOURNAL   Gastroenterology 124:34-9 (2003)
            DOI:10.1053/gast.2003.50009
REFERENCE   PMID:11562503
  AUTHORS   Stumpel F, Burcelin R, Jungermann K, Thorens B
  TITLE     Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum.
  JOURNAL   Proc Natl Acad Sci U S A 98:11330-5 (2001)
            DOI:10.1073/pnas.211357698
REFERENCE   PMID:15546855
  AUTHORS   Wright EM, Loo DD, Hirayama BA, Turk E
  TITLE     Surprising versatility of Na+-glucose cotransporters: SLC5.
  JOURNAL   Physiology (Bethesda) 19:370-6 (2004)
            DOI:10.1152/physiol.00026.2004
REFERENCE   PMID:12750891
  AUTHORS   Uldry M, Thorens B
  TITLE     The SLC2 family of facilitated hexose and polyol transporters.
  JOURNAL   Pflugers Arch 447:480-9 (2004)
            DOI:10.1007/s00424-003-1085-0
REFERENCE   PMID:7555019
  AUTHORS   Van Beers EH, Buller HA, Grand RJ, Einerhand AW, Dekker J
  TITLE     Intestinal brush border glycohydrolases: structure, function, and development.
  JOURNAL   Crit Rev Biochem Mol Biol 30:197-262 (1995)
            DOI:10.3109/10409239509085143
REFERENCE   PMID:5089892
  AUTHORS   Marsh MN
  TITLE     Digestive-absorptive functions of the enterocyte.
  JOURNAL   Ann R Coll Surg Engl 48:356-68 (1971)
REFERENCE   PMID:12583961
  AUTHORS   Guarner F, Malagelada JR
  TITLE     Gut flora in health and disease.
  JOURNAL   Lancet 361:512-9 (2003)
            DOI:10.1016/S0140-6736(03)12489-0
REFERENCE   PMID:11427691
  AUTHORS   Topping DL, Clifton PM
  TITLE     Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides.
  JOURNAL   Physiol Rev 81:1031-64 (2001)
            DOI:10.1152/physrev.2001.81.3.1031
REL_PATHWAY hsa04530  Tight junction
            hsa04742  Taste transduction
            hsa04970  Salivary secretion
            hsa04972  Pancreatic secretion
KO_PATHWAY  ko04973
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