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 (or sodium-glucose linked transporter, 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. Glucose is never secreted by a healthy nephron.

Types

The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family. In addition to SGLT1 and SGLT2, there are five other members in the human protein family SLC5A, several of which may also be sodium-glucose transporters.^[1]

Gene	Protein	Acronym	Tissue distribution in proximal tubule^[2]	Na⁺:Glucose Co-transport ratio	Contribution to glucose reabsorption (%)^[3]
SLC5A1	Sodium/GLucose coTransporter 1	SGLT1	S3 segment	2:1	10
SLC5A2	Sodium/GLucose coTransporter 2	SGLT2	predominantly in the S1 and S2 segments	1:1	90

SGLT2 inhibitors for diabetes

Main article: Gliflozin

SGLT2 inhibitors, also called gliflozins,^[4] are used in the treatment of type II diabetes. Examples include dapagliflozin (Farxiga,Farxiga), canagliflozin (Invokana) and empagliflozin (Jardiance).

Function

Firstly, an Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule cell uses ATP molecules to move 3 sodium ions outward into the blood, while bringing in 2 potassium ions. This action creates a downhill sodium ion gradient from the outside to the inside of the proximal tubule cell (that is, in comparison to both the blood and the tubule itself).

The SGLT proteins use the energy from this downhill sodium ion gradient created by the ATPase pump to transport glucose across the apical membrane, against an uphill glucose gradient. These co-transporters are an example of secondary active transport. Members of the GLUT family of glucose uniporters then transport the glucose across the basolateral membrane, and into the peritubular capillaries. Because sodium and glucose are in the same direction across the membrane, SGLT1 and SGLT2 are known as symporters.

History

In August 1960, in Prague, Robert K. Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.^[5]

Crane's discovery of cotransport was the first-ever proposal of flux coupling in biology.^[6]^[7]

References

↑ Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509
↑ 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.
↑ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
↑ 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 [7]. 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.

External links

Sodium-Glucose Transport Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)

Membrane transport protein: ion pumps, ATPases / ATP synthase (TC 3A2-3A3)

F-, V-, and A-type ATPase (3.A.2)

H⁺ (F-type)	H⁺ transporting, mitochondrial: ATP5A1 ATP5B ATP5C1 ATP5C2 ATP5D ATP5E ATP5F1 ATP5G1 ATP5G2 ATP5G3 ATP5H ATP5I ATP5J ATP5J2 ATP5L ATP5L2 ATP5O ATP5S

H⁺ (V-type)	H⁺ transporting, lysosomal: ATP6AP1 ATP6AP2 ATP6V1A ATP6V1B1 ATP6V1B2 ATP6V1C1 ATP6V1C2 ATP6V1D ATP6V1E1 ATP6V1E2 ATP6V1F ATP6V1G1 ATP6V1G2 ATP6V1G3 ATP6V1H ATP6V0A1 ATP6V0A2 ATP6V0A4 ATP6V0B ATP6V0C ATP6V0D1 ATP6V0D2 ATP6V0E ATP6V0E1 TCIRG1

A-ATPase	found in Archea

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.3.1.2: H⁺/K⁺
H⁺/K⁺ exchanging: ATP4A
ATP4B

3.A.3.1.4: H⁺/K⁺ transporting, nongastric: ATP12A

3.A.3.2: Ca²⁺ (SERCA, PMCA, SPCA) / Ca²⁺ transporting: ATP2A1
ATP2A2
ATP2A3
ATP2B1
ATP2B2
ATP2B3
ATP2B4
ATP2C1

3.A.3.5: Cu²⁺ transporting: ATP7A
ATP7B

3.A.3.8.8: flippase: ATP8A2

Other/ungrouped:

Na⁺/K⁺ – H⁺

Mg²⁺ transporting: ATP3
Class I, type 8: ATP8A1
ATP8B1
ATP8B2
ATP8B3
ATP8B4
Class II, type 9: ATP9A
ATP9B
Class V, type 10: ATP10A
ATP10B
ATP10D
Class VI, type 11: ATP11A
ATP11B
ATP11C
type 13: ATP13A1
ATP13A2
ATP13A3
ATP13A4
ATP13A5

see also ATPase disorders

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1):	high affinity glutamate and neutral amino-acid transporter SLC1A1 2 3 4 5 6 7

(2):	facilitative GLUT transporter SLC2A1 2 3 4 5 6 7 8 9 10 11 12 13 14

(3):	heavy subunits of heterodimeric amino-acid transporters SLC3A1 2

(4):	bicarbonate transporter SLC4A1 2 3 4 5 6 7 8 9 10 11

(5):	sodium glucose cotransporter SLC5A1 2 3 4 5 6 7 8 9 10 11 12

(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

(10):	sodium bile salt cotransport SLC10A1 SLC10A2 SLC10A3 SLC10A4 SLC10A5 SLC10A6 SLC10A7 10A1 10A2 10A3 10A7

SLC11–20

(11):	proton coupled metal ion transporter SLC11A1 SLC11A2 11A3

(12):	electroneutral cation-Cl cotransporter SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9

(13):	human Na⁺-sulfate/carboxylate cotransporter SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5

(14):	urea transporter SLC14A1 SLC14A2

(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 1 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC17A9

(18):	vesicular monoamine transporter SLC18A1 SLC18A2 SLC18A3

(19):	folate/thiamine transporter SLC19A1 SLC19A2 SLC19A3

(20):	type III Na⁺-phosphate cotransporter SLC20A1 SLC20A2

SLC21–30

(21):	Organic anion-transporting polypeptide 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

(23):	Na+-dependent ascorbic acid transporter SLC23A1 SLC23A2 SLC23A3 SLC23A4

(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

(27):	fatty acid transport proteins SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6

(28):	Na⁺-coupled nucleoside transport (SLC28A1 SLC28A2 SLC28A3

(29):	facilitative nucleoside transporter SLC29A1 SLC29A2 SLC29A3 SLC29A4

(30):	zinc efflux SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6 SLC30A7 SLC30A8 SLC30A9 SLC30A10

SLC31–40

(31):	copper transporter SLC31A1

(32):	Vesicular glutamate transporter 1 SLC32A1

(33):	Acetyl-CoA transporter SLC33A1

(34):	type II Na⁺-phosphate cotransporter SLC34A1 SLC34A2 SLC34A3

(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 SLC36A436A2

(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

SLC41–48

(41):	Magnesium transporter E SLC41A1 SLC41A2 SLC41A3

(42):	Ammonia transporter RhAG RhBG RhCG

(43):	Na⁺-independent, system-L like amino-acid transporter SLC43A1 SLC43A2 SLC43A3

(44):	Choline-like transporter SLC44A1 SLC44A2 SLC44A3 SLC44A4 SLC44A5

(45):	Putative sugar transporter SLC45A1 SLC45A2 SLC54A3 SLC45A4

(46):	Folate transporter SLC46A1 SLC46A2

(47):	multidrug and toxin extrusion SLC47A1 SLC47A2

(48):	Heme transporter

SLCO1–4

O1A2 O1B1 O1B3 O2B1 O431 O4A1

Ion pumps

Symporter, Cotransporter	Na⁺/K⁺,Cl⁻ Na⁺/P_i3 Na⁺/Cl⁻ Na⁺/glucose Na⁺/I⁻ Cl⁻/K⁺ 4 5

Antiporter (exchanger)	Na⁺/H⁺ Na⁺/Ca²⁺ Na⁺/(Ca²⁺-K⁺) - Cl⁻/HCO− 3 (Band 3) Cl⁻-formate Cl⁻-oxalate

see also solute carrier disorders

This article is issued from Wikipedia - version of the Wednesday, March 02, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.