Sodium-glucose transport proteins
solute carrier family 5 (sodium/glucose cotransporter), member 1 Identifiers Symbol SLC5A1 Alt. symbols SGLT1 Entrez 6523 HUGO 11036 OMIM 182380 RefSeq NM_000343 UniProt P13866 Other data Locus Chr. 22 q13.1 solute carrier family 5 (sodium/glucose cotransporter), member 2 Identifiers Symbol SLC5A2 Alt. symbols SGLT2 Entrez 6524 HUGO 11037 OMIM 182381 RefSeq NM_003041 UniProt P31639 Other data Locus Chr. 16 p11.2 solute carrier family 5 (low affinity glucose cotransporter), member 4 Identifiers Symbol SLC5A4 Alt. symbols SGLT3, SAAT1, DJ90G24.4 Entrez 6527 HUGO 11039 RefSeq NM_014227 UniProt Q9NY91 Other data Locus Chr. 22 q12.1-12.3
Sodium-dependent glucose cotransporters (SGLT) are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron (SGLT2 in PCT and SGLT1 in PST). They contribute to renal glucose reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be reabsorbed along the nephron (98% in PCT, via SGLT2). In case of too high plasma glucose concentration (hyperglycemia), glucose is excreted in urine (glucosuria); because SGLT are saturated with the filtered monosaccharide. One must know that glucose is never secreted by the nephron.
The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family.
Gene Protein Acronym Tissue distribution
in proximal tubule
Contribution to glucose
SGLT1 S3 segment 2:1 10 SLC5A2 Sodium/GLucose
SGLT2 predominately in the
S1 and S2 segments
Including SGLT1 and SGLT2, there are total seven members in the human protein family SLC5A, several of which may also be sodium-glucose transporters.
First, the Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule, cell actively (requires ATP) transports sodium from this cell into the peritubular capillary. This creates a downhill sodium gradient inside the proximal tubule cell. The SGLT proteins use the energy from this downhill sodium gradient created by the ATPase pump to transport glucose across the apical membrane against an uphill glucose gradient. Therefore, these co-transporters are an example of secondary active transport. (The GLUT uniporters then transport the glucose across the basolateral membrane, into the peritubular capillaries.) Both SGLT1 and SGLT2 are known as symporters, since both sodium and glucose are transported in the same direction across the membrane.
Discovery of sodium-glucose cotransport
- ^ Wright EM, Hirayama BA, Loo DF (January 2007). "Active sugar transport in health and disease". J. Intern. Med. 261 (1): 32–43. doi:10.1111/j.1365-2796.2006.01746.x. PMID 17222166.
- ^ Wright EM (January 2001). "Renal Na(+)-glucose cotransporters". Am. J. Physiol. Renal Physiol. 280 (1): F10–8. PMID 11133510.
- ^ Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509
- ^ Miller D, Bihler I (1961). "The restrictions on possible mechanisms of intestinal transport of sugars". In Kleinzeller A. Kotyk A. Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Czech Academy of Sciences & Academic Press. pp. 439–449.
- ^ Wright EM, Turk E (February 2004). "The sodium/glucose cotransport family SLC5". Pflugers Arch. 447 (5): 510–8. doi:10.1007/s00424-003-1063-6. PMID 12748858. "Crane in 1961 was the first to formulate the cotransport concept to explain active transport . Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was [is] coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type."
- ^ Boyd CA (March 2008). "Facts, fantasies and fun in epithelial physiology". Exp. Physiol. 93 (3): 303–14. doi:10.1113/expphysiol.2007.037523. PMID 18192340. "p. 304. “the insight from this time that remains in all current text books is the notion of Robert Crane published originally as an appendix to a symposium paper published in 1960 (Crane et al. 1960). The key point here was 'flux coupling', the cotransport of sodium and glucose in the apical membrane of the small intestinal epithelial cell. Half a century later this idea has turned into one of the most studied of all transporter proteins (SGLT1), the sodium–glucose cotransporter."
F- and V-type ATPase (3.A.2) P-type ATPase (3.A.3)
- 3.A.3.1.1: Na+/K+ transporting: ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP1B4, ATP1G1
- 3.A.3.1.4: H+/K+ transporting, nongastric: ATP12A
- 3.A.3.2: Ca+ (SERCA, PMCA, SPCA) / Ca++ transporting: ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, ATP2C1
- 3.A.3.8.8: flippase: ATP8A2
By group SLC1–10
- (6) sodium- and chloride- dependent sodium:neurotransmitter symporters (SLC6A1, SLC6A2, SLC6A3, SLC6A4, SLC6A5, SLC6A6, SLC6A7, SLC6A8, SLC6A9, SLC6A10, SLC6A11, SLC6A12, SLC6A13, SLC6A14, SLC6A15, SLC6A16, SLC6A17, SLC6A18, SLC6A19, SLC6A20)
- (7) cationic amino-acid transporter/glycoprotein-associated (SLC7A1, SLC7A2, SLC7A3, SLC7A4) glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A9, SLC7A10, SLC7A11, SLC7A13, SLC7A14)
- (8) Na+/Ca2+ exchanger (SLC8A1, SLC8A2, SLC8A3)
- (9) Na+/H+ exchanger (SLC9A1, SLC9A2, SLC9A3, SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9A10, SLC9A11)
- (12) electroneutral cation-Cl cotransporter (SLC12A1, SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7, SLC12A8, SLC12A9)
- (15) proton oligopeptide cotransporter (SLC15A1, SLC15A2, SLC15A3, SLC15A4)
- (16) monocarboxylate transporter (SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14)
- (17) vesicular glutamate transporter (SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC17A9)
- (21) organic anion transporting (SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B4, SLCO1C1) (SLCO2A1, SLCO2B1) (SLCO3A1) (SLCO4A1, SLCO4C1) (SLCO5A1) (SLCO6A1)
- (22) organic cation/anion/zwitterion transporter (SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC22A10, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC22A19, SLC22A20)
- (24) Na+/(Ca2+-K+) exchanger (SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC24A6)
- (25) mitochondrial carrier (SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, SLC25A7, SLC25A8, SLC25A9, SLC25A10, SLC25A11, SLC25A12, SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A30, SLC25A31, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46)
- (26) multifunctional anion exchanger (SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A10, SLC26A11)
- (32) vesicular inhibitory amino-acid transporter (SLC32A1)
- (33) Acetyl-CoA transporter (SLC33A1)
- (35) nucleoside-sugar transporter (SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5) (SLC35B1, SLC35B2, SLC35B3, SLC35B4) (SLC35C1, SLC35C2) (SLC35D1, SLC35D2, SLC35D3) (SLC35E1, SLC35E2, SLC35E3, SLC35E4)
- (36) proton-coupled amino-acid transporter (SLC36A1, SLC36A2, SLC36A3, SLC36A4)36A2 ·
- (37) sugar-phosphate/phosphate exchanger (SLC37A1, SLC37A2, SLC37A3, SLC37A4)
- (38) System A & N, sodium-coupled neutral amino-acid transporter (SLC38A1, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6, SLC38A10)
- (39) metal ion transporter (SLC39A1, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A14)
- (40) basolateral iron transporter (SLC40A1)
- (41) MgtE-like magnesium transporter (SLC41A1, SLC41A2, SLC41A3)
- (43) Na+-independent, system-L like amino-acid transporter (SLC43A1, SLC43A2, SLC43A3)
- (45) Putative sugar transporter (SLC45A1, SLC45A2, SLC54A3, SLC45A4)
- (46) Folate transporter (SLC46A1, SLC46A2)
- (48) Heme transporter
SLCO1–4 Ion pumps
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