Sodium/glucose cotransporter 1 (SGLT1) also known assolute carrier family 5 member 1 is aprotein in humans that is encoded by theSLC5A1gene[4][5] which encodes the production of the SGLT1 protein to line theabsorptive cells in thesmall intestine and the epithelial cells of thekidney tubules of thenephron for the purpose of glucose uptake into cells.[6] Recently, it has been seen to have functions that can be considered as promising therapeutic target to treat diabetes and obesity.[7] Through the use of the sodium glucose cotransporter 1 protein, cells are able to obtain glucose which is further utilized to make and store energy for the cell.
The sodium glucose cotransporter 1 is classified as anintegral membrane protein that is made up of 14alpha-helices constructed from the folding of 482-718 amino acid residues with both theN andC-terminal residing upon the extracellular side of the plasma membrane.[8] It is hypothesized that the protein containsprotein kinase A andprotein kinase C phosphorylation sites, which serve to regulate the proteins conformational shape through phosphorylation of amino acids withATP.[8][9]
Glucose transporters are integralmembrane proteins that mediate the transport ofglucose and structurally related substances acrosscellular membranes. Two families of glucose transporter have been identified: thefacilitated diffusion glucose transporter family (GLUT family), also known asuniporters, and the sodium-dependent glucose transporter family (SGLT family), also known ascotransporters orsymporters.[10] TheSLC5A1 gene encodes the sodium glucose cotransporter protein that is involved in the facilitated transport of glucose andgalactose intoeukaryotic andprokaryotic cells.[5] The role of the sodium-glucose cotransporter 1 is to absorbD-glucose andD-galactose from thebrush-border membrane of the small intestines,[11][12] while also exchanging sodium ions and glucose from the tubule of the nephron.[13] The SGLT1 protein is able to uptake glucose through cellular membranes through coupling the energy generated from cotransporting 2 sodium ions with glucose through a symport mechanism.[14] This protein does not use ATP as energy source.[14]
The sodium glucose cotransporter is original arranged with an outward-facing conformation with open receptors in preparation for 2 sodium ions and glucose to simultaneously bind.[6] Once bound, the protein receptor will change conformation to an occluded conformation, which prevents the dissociation of the sodium ions and glucose.[6] The protein will then change conformations once more to an inward-facing conformation in which allows sodium and glucose to dissociate.[6] The protein then returns to the outward-facing conformation state, ready to bind more sodium ions and glucose.[6]
Co-transport proteins of mammalian cell membranes had eluded efforts of purification with classical biochemical methods until the late 1980s. These proteins had proven difficult to isolate because they contain hydrophilic and hydrophobic sequences and exist in membranes only in very low abundance (<0.2% of membrane proteins). The rabbit form of SGLT1 was the first mammalian co-transport protein ever to be cloned and sequenced, and this was reported in 1987.[15] To circumvent the difficulties with traditional isolation methods, a novelexpression cloning technique was used. Size-fractionation of large amounts of rabbit intestinal mRNA with preparativegel electrophoresis were then sequentially injected intoXenopus oocytes to ultimately find the RNA species that induced the expression of sodium-glucose cotransport.[15]
SLC5A1 is medically relevant because of its role in the absorption of glucose and sodium, however, mutations in the gene can cause medical implications. Amissense mutation[4] in theSLC5A1 gene of exon 1 can cause problems creating the SGLT1 protein, leading to a very rareglucose-galactose malabsorption disease.[4] This is because the mutation destroys the transport function.[4] Glucose-galactose malabsorption occurs when the lining of the intestinal cells cannot take in glucose and galactose which prevents the use of those molecules in catabolism and anabolism. The disease has symptoms that consist of watery and/or acidicdiarrhea which is the result of water retention in the intestinal lumen and osmotic loss created by non-absorbed glucose, galactose and sodium.[16] Patients must stick to a diet devoid of these two sugars, or life-threatening diarrhea will occur.[17]
In humans without this genetic disorder, SGLT1 is key to the operation oforal rehydration therapy. By adding sodium and glucose to water, the co-transporter is allowed to transport all three, helping to speed up water absorption.[18]
^abcdeLodish H, Berk A, Kaiser CA, Krieger M, Bretscher A, Ploegh H, et al. (April 2016).Molecular cell biology (Eighth ed.). New York.ISBN9781464183393.OCLC949909675.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: overridden setting (link)
^Avendaño C, Menéndez JC (2008). "Drugs That Inhibit Signalling Pathways for Tumor Cell Growth and Proliferation".Medicinal Chemistry of Anticancer Drugs. Elsevier. pp. 251–305.doi:10.1016/b978-0-444-52824-7.00009-3.ISBN9780444528247.
^Hamilton KL, Butt AG (December 2013). "Glucose transport into everted sacs of the small intestine of mice".Advances in Physiology Education.37 (4):415–426.doi:10.1152/advan.00017.2013.PMID24292921.S2CID8525585.
Turk E, Klisak I, Bacallao R, Sparkes RS, Wright EM (September 1993). "Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1".Genomics.17 (3):752–754.doi:10.1006/geno.1993.1399.PMID8244393.
Martín MG, Turk E, Lostao MP, Kerner C, Wright EM (February 1996). "Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption".Nature Genetics.12 (2):216–220.doi:10.1038/ng0296-216.PMID8563765.S2CID2372635.
Obermeier S, Hüselweh B, Tinel H, Kinne RH, Kunz C (October 2000). "Expression of glucose transporters in lactating human mammary gland epithelial cells".European Journal of Nutrition.39 (5):194–200.doi:10.1007/s003940070011.PMID11131365.S2CID22976632.
Roll P, Massacrier A, Pereira S, Robaglia-Schlupp A, Cau P, Szepetowski P (February 2002). "New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families".Gene.285 (1–2):141–148.doi:10.1016/S0378-1119(02)00416-X.PMID12039040.
