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Molecular biology of glucose transporters: Classification, structure and distribution

Abstract:

Hexoses like glucose, galactose and fructose serve as basic fuel molecules for eucaryotic cells. These molecules are un-able to diffuse across cellular membranes, and require trans-porter proteins for entry into and exit from cells. Three dis-tinct groups of hexose transporters have been identified and classified based on their dependence on cellular energy and its chemistry structure. Each of the transporters has different affinities for glucose and the other hexoses, which largely dic-tates their function. The hexose transporters are large integral membrane proteins. Based on the deduced amino acid se-quences of their cloned cDNAs, they have similar structures, consisting of 12 or 14 membrane-spanning regions with cyto-plasmic C-terminal and N-terminal tails. Also, they all appear to be glycosylated on one of the extracellular loops. Transport of sugars across membranes appears to result from a series of conformational changes which "flips" the transporter be-tween alternate states with the substrate binding site either facing the extracellular or cytoplasmic side of the membrane. Transport in either direction is thus possible, depending on relative substrate concentrations on either side of the mem-brane. The original protein, GLUT1, was identified in molecu-lar term's 12 years ago. In the subsequent 15 years, a family of related transporters was identified (GLUTs 1-14). The impact of these discoveries is better realized when we list a sample of the processes that utilize different members of the GLUT fam-ily: control of glycemia; insulin dependent glucose utilization; transport pathways in brain neurons and glia; mechanisms of glucose and fructose uptake in the intestinal track; reabsorp-tion of glucose in kidney tubules and jejunum; maturation of transporters during lactation and weaning; sensing of glucose levels by the pancreas and the liver; control of glucose uptake in high fat feeding; glucose uptake in response to exercise, adaptive response of energy metabolism to cellular stress.