Intestinal absorption (Homo sapiens)

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Bibliography

1. Weinglass AB, Köhler MG, Nketiah EO, Liu J, Schmalhofer W, Thomas A, Williams B, Beers L, Smith L, Hafey M, Bleasby K, Leone J, Tang YS, Braun M, Ujjainwalla F, McCann ME, Kaczorowski GJ, Garcia ML.; ''Madin-Darby canine kidney II cells: a pharmacologically validated system for NPC1L1-mediated cholesterol uptake.''; PubMed Europe PMC Scholia
2. Veyhl M, Keller T, Gorboulev V, Vernaleken A, Koepsell H.; ''RS1 (RSC1A1) regulates the exocytotic pathway of Na+-D-glucose cotransporter SGLT1.''; PubMed Europe PMC Scholia
3. Wright EM, Loo DD, Hirayama BA, Turk E.; ''Surprising versatility of Na+-glucose cotransporters: SLC5.''; PubMed Europe PMC Scholia
4. Wu L, Fritz JD, Powers AC.; ''Different functional domains of GLUT2 glucose transporter are required for glucose affinity and substrate specificity.''; PubMed Europe PMC Scholia
5. Pessin JE, Bell GI.; ''Mammalian facilitative glucose transporter family: structure and molecular regulation.''; PubMed Europe PMC Scholia
6. Santer R, Schneppenheim R, Dombrowski A, Götze H, Steinmann B, Schaub J.; ''Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome.''; PubMed Europe PMC Scholia
7. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA.; ''The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1).''; PubMed Europe PMC Scholia
8. Burant CF, Takeda J, Brot-Laroche E, Bell GI, Davidson NO.; ''Fructose transporter in human spermatozoa and small intestine is GLUT5.''; PubMed Europe PMC Scholia
9. Davidson NO, Hausman AM, Ifkovits CA, Buse JB, Gould GW, Burant CF, Bell GI.; ''Human intestinal glucose transporter expression and localization of GLUT5.''; PubMed Europe PMC Scholia
10. Quick M, Tomasevic J, Wright EM.; ''Functional asymmetry of the human Na+/glucose transporter (hSGLT1) in bacterial membrane vesicles.''; PubMed Europe PMC Scholia
11. Thorens B, Cheng ZQ, Brown D, Lodish HF.; ''Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells.''; PubMed Europe PMC Scholia
12. Martín MG, Turk E, Lostao MP, Kerner C, Wright EM.; ''Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption.''; PubMed Europe PMC Scholia
13. Colville CA, Seatter MJ, Jess TJ, Gould GW, Thomas HM.; ''Kinetic analysis of the liver-type (GLUT2) and brain-type (GLUT3) glucose transporters in Xenopus oocytes: substrate specificities and effects of transport inhibitors.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
CHOL	Metabolite	CHEBI:16113 (ChEBI)
EZE	Metabolite	CHEBI:49040 (ChEBI)
EZE	Metabolite	CHEBI:49040 (ChEBI)
Fru	Metabolite	CHEBI:15824 (ChEBI)
Fru, Gal, Glc	Complex	R-ALL-189219 (Reactome)
Fru, Gal, Glc	Complex	R-ALL-189246 (Reactome)
Fru	Metabolite	CHEBI:15824 (ChEBI)
GLUT2 / SLC2A2 tetramer	Complex	R-HSA-70422 (Reactome)
Gal	Metabolite	CHEBI:17118 (ChEBI)
Gal, Glc	Complex	R-ALL-189227 (Reactome)
Gal, Glc	Complex	R-ALL-189254 (Reactome)
Glc	Metabolite	CHEBI:17925 (ChEBI)
NPC1L1-1	Protein	Q9UHC9-2 (Uniprot-TrEMBL)
NPC1L1-1	Protein	Q9UHC9-2 (Uniprot-TrEMBL)
NPC1L1:ezetimibe complex	Complex	R-HSA-265464 (Reactome)
Na+	Metabolite	CHEBI:29101 (ChEBI)
RSC1A1	Protein	Q92681 (Uniprot-TrEMBL)
SLC2A2	Protein	P11168 (Uniprot-TrEMBL)
SLC2A5	Protein	P22732 (Uniprot-TrEMBL)
SLC5A1	Protein	P13866 (Uniprot-TrEMBL)
phytosterols	Metabolite	CHEBI:26125 (ChEBI)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	CHOL	Arrow	R-HSA-265443 (Reactome)
CHOL			R-HSA-265443 (Reactome)
EZE			R-HSA-265456 (Reactome)
	Fru, Gal, Glc	Arrow	R-HSA-189242 (Reactome)
Fru, Gal, Glc			R-HSA-189242 (Reactome)
	Fru	Arrow	R-HSA-189222 (Reactome)
Fru			R-HSA-189222 (Reactome)
GLUT2 / SLC2A2 tetramer		mim-catalysis	R-HSA-189242 (Reactome)
	Gal, Glc	Arrow	R-HSA-8932955 (Reactome)
Gal, Glc			R-HSA-8932955 (Reactome)
NPC1L1-1			R-HSA-265456 (Reactome)
NPC1L1-1		mim-catalysis	R-HSA-265443 (Reactome)
NPC1L1-1		mim-catalysis	R-HSA-265545 (Reactome)
	NPC1L1:ezetimibe complex	Arrow	R-HSA-265456 (Reactome)
	Na+	Arrow	R-HSA-8932955 (Reactome)
Na+			R-HSA-8932955 (Reactome)
			R-HSA-189222 (Reactome)	The reversible transport of extracellular fructose into the cytosol is mediated by SLC2A5, also known as GLUT5. In the small intestine, SLC2A5 is localized on the lumenal surfaces of enterocytes (Davidson et al. 1992) and mediates the uptake of dietary fructose, which can be released into the circulation in a separate transport step mediated by basolaterally localized SLC2A2 (GLUT2). The specificity of SLC2A5 has been worked out by studying sugar transport in Xenopus oocytes expressing recombinant human SLC2A5 protein (Burant et al. 1992).
			R-HSA-189242 (Reactome)	The reversible facilitated diffusion of fructose, galactose, and glucose from the cytosol to the extracellular space is mediated by tetrameric SLC2A2 (also known as GLUT2) transporter in the plasma membrane. In the epithelial cells of the small intestine, the basolateral localization of SLC2A2 (Thorens et al. 1990) enables hexose sugars derived from the diet and taken up by the action of the SLC5A1 (SGLT1) and SLC2A5 (GLUT5) transporters to be released into the circulation. The specificity of the SLC2A2 transporter has been established directly through biochemical assays of purified recombinant proteins (Colville et al. 1993; Wu et al. 1998) and indirectly through studies of patients deficient in SLC2A2 transporter protein (Santer et al. 1997).
			R-HSA-265443 (Reactome)	Dietary cholesterol is taken up into enterocytes from the gut lumen in a reaction mediated by plasma membrane-associated NPC1L1 protein. This role for NPC1L1 was first observed in studies of a mouse model system (Altman et al. 2004). Subsequent studies of human cultured cells confirmed the participation of NPC1L1 in cholesterol transport across membranes but suggested that this transport process might not be a major factor in dietary cholesterol uptake (Davies et al. 2005). Detailed studies in Maden-Darby canine kidney cells, both mediated by endogenous (canine) NPC1L1 and by overexpressed human protein, indicate a major role for NPC1L1 in the uptake of extracellular cholesterol. These studies have also shown that ezetimibe binds both human and canine proteins and renders them incapable of mediating cholesterol uptake. The molecular mechanisms of cholesterol transport and ezetimibe inhibition, however, remain unclear (Weinglass et al. 2008).
			R-HSA-265456 (Reactome)	Human NPC1L1, associated with the plasma membrane, binds ezetimibe and becomes incapable of mediating cholesterol uptake. The molecular mechanisms of cholesterol transport and ezetimibe inhibition, however, remain unclear (Garcia-Calvo et al. 2005; Weinglass et al. 2008).
			R-HSA-265545 (Reactome)	Dietary phytosterols (sterols derived from plants) are taken up into enterocytes from the gut lumen. The reaction is thought to be mediated by plasma membrane-associated NPC1L1 protein. Detailed studies in Maden-Darby canine kidney cells, both mediated by endogenous (canine) NPC1L1 and by overexpressed human protein, indicate a major role for NPC1L1 in the uptake of extracellular sterol. These studies have also shown that ezetimibe binds both human and canine proteins and renders them incapable of mediating sterol uptake. The molecular mechanisms of cholesterol transport and ezetimibe inhibition, however, remain unclear (Weinglass et al. 2008).
			R-HSA-8932955 (Reactome)	The transport of extracellular glucose (Glc) and galactose (Gal) into the cytosol, coupled to the uptake of two sodium ions for each hexose transported, is mediated by sodium/glucose cotransporter 1 (SLC5A1, also known as SGLT1), localized on the luminal surfaces of enterocytes (Wright et al. 2004). The specificity of SLC5A1 has been worked out by studying sugar transport in plasma membrane vesicles containing recombinant human SLC5A1 protein (Quick et al. 2003). Consistent with these in vitro results, children lacking functional SLC5A1 protein fail to absorb dietary glucose and galactose (Martin et al. 1996). The transport activity of SLC5A1 was decreased upon co-expression of regulatory solute carrier protein family 1 member 1 (RSC1A1, aka RS1). RSC1A1 exhibits glucose-dependent, short-term inhibition of SLC5A1 by inhibiting the release of vesicles from the trans-Golgi network (Veyhl et al. 2006).
RSC1A1		TBar	R-HSA-8932955 (Reactome)
SLC2A5		mim-catalysis	R-HSA-189222 (Reactome)
SLC5A1		mim-catalysis	R-HSA-8932955 (Reactome)
	phytosterols	Arrow	R-HSA-265545 (Reactome)
phytosterols			R-HSA-265545 (Reactome)