Cellular hexose transport (Homo sapiens)
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Description
Hexoses, notably fructose, glucose, and galactose, generated in the lumen of the small intestine by breakdown of dietary carbohydrate are taken up by enterocytes lining the microvilli of the small intestine and released from them into the blood. Uptake into enterocytes is mediated by two transporters localized on the lumenal surfaces of the cells, SGLT1 (glucose and galactose, together with sodium ions) and GLUT5 (fructose). GLUT2, localized on the basolateral surfaces of enterocytes, mediates the release of these hexoses into the blood (Wright et al. 2004). GLUT2 may also play a role in hexose uptake from the gut lumen into enterocytes when the lumenal content of monosaccharides is very high (Kellet & Brot-Laroche 2005) and GLUT5 mediates fructose uptake from the blood into cells of the body, notably hepatocytes.<p>Cells take up glucose by facilitated diffusion, via glucose transporters (GLUTs) associated with the plasma membrane, a reversible reaction. Four tissue-specific GLUT isoforms are known. Glucose in the cytosol is phosphorylated by tissue-specific kinases to yield glucose 6-phosphate, which cannot cross the plasma membrane because of its negative charge. In the liver, this reaction is catalyzed by glucokinase which has a low affinity for glucose (Km about 10 mM) but is not inhibited by glucose 6-phosphate. In other tissues, this reaction is catalyzed by isoforms of hexokinase. Hexokinases are feedback-inhibited by glucose 6-phosphate and have a high affinity for glucose (Km about 0.1 mM). Liver cells can thus accumulate large amounts of glucose 6-phosphate but only when blood glucose concentrations are high, while most other tissues can take up glucose even when blood glucose concentrations are low but cannot accumulate much intracellular glucose 6-phosphate. These differences are consistent with the view that that the liver functions to buffer blood glucose concentrations, while most other tissues take up glucose to meet immediate metabolic needs.<p>Glucose 6-phosphatase, expressed in liver and kidney, allows glucose 6-phosphate generated by gluconeogenesis (both tissues) and glycogen breakdown (liver) to leave the cell. The absence of glucose 6-phosphatase from other tissues makes glucose uptake by these tissues essentially irreversible, consistent with the view that cells in these tissues take up glucose for local metabolic use.<p>Class II facilitative transporters consist of GLUT5, 7, 9 and 11 (Zhao & Keating 2007, Wood & Trayhurn 2003). View original pathway at Reactome.</div>
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SLC2A11 encodes GLUT11 (Doege H et al, 2001), another member of the class II facilitative glucose transporters. It has the highest similarity with GLUT5 and in humans, three isoforms are expressed (GLUT11A-C) (Sasaki T et al, 2001). Human GLUT11 has been shown to transport glucose and fructose but not galactose when expressed in Xenopus oocytes ( Scheepers A et al, 2005).
Four class III facilitative transporters can transport glucose. SLC2A6 encodes GLUT6, expressed mainly in brain, spleen and leucocytes (Doege H et al, 2000a). In literature, this protein is incorrectly described as GLUT9. SLC2A8 encodes GLUT8 and is expressed in brain, testis and adipose tissue (Doege H et al, 2000b). SLC2A10 (located in the Type 2 diabetes-linked region of human chromosome 20q12-13.1) encodes GLUT10, a transporter with high affinity for glucose (McVie-Wylie AJ et al, 2001) . GLUT10 is highly expressed in liver and pancreas but is present in most tissues in lower levels. Defects in SLC2A10 are the cause of arterial tortuosity syndrome (ATS), an autosomal recessive disorder characterized by tortuosity and elongation of major arteries, often resulting in death at a young age (Coucke PJ et al, 2006). SLC2A12 encodes GLUT12, which is highly expressed in skeletal muscle, heart and prostate, with lower levels in brain, placenta and kidney. It was originally cloned from the human breast cancer cell line MCF-7 (Rogers S et al, 2002).