This passive system is mediated by a family of 14 glucose transporter (GLUT) isoforms found in cell membranes. They are designated GLUT-1 to GLUT-14. These monomeric protein transporters exist in the membrane in two conformational states (Fig. 8.10). Extracellular glucose binds to the transporter, which then alters its conformation, transporting glucose across the cell membrane via facilitated diffusion. Because GLUT transport one molecule at a time, they are uniporters.
1.
Tissue specificity: GLUT display a tissue-specific pattern of expression.
For example, GLUT-3 is the primary isoform in neurons. GLUT-1 is abundant in RBC and the blood–brain barrier but is low in adult muscle, whereas GLUT-4 is abundant in muscle and adipose tissue. [Note: The number of GLUT-4 transporters active in these tissues is increased by insulin. (See p. 311 for a discussion of insulin and glucose transport.)] GLUT-2 is abundant in the liver, kidneys, and pancreatic β cells. The other GLUT isoforms also have tissue-specific distributions.
2.
Specialized functions: In facilitated diffusion, transporter-mediated glucose movement is down a concentration gradient (that is, from a high concentration to a lower one, therefore requiring no energy). For example, GLUT-1, GLUT-3, and GLUT-4 are primarily involved in glucose uptake from the blood. In contrast, GLUT-2, in the liver and kidneys, can either transport glucose into these cells when blood glucose levels are high or transport glucose from these cells when blood glucose levels are low (for example, during fasting). GLUT-5 is unusual in that it is the primary transporter for fructose (not glucose) in the small intestine and the testes (see p. 87).
B. Sodium-and ATP-dependent cotransport system
This energy-requiring process transports glucose against (up) its concentration gradient (that is, from low extracellular concentrations to higher intracellular concentrations) as Na+ is transported down its electrochemical gradient. [Note: The gradient is created by the Na+potassium (K+) ATPase (see Fig. 7.10, p. 87).] Because this secondary active transport process requires the concurrent uptake (symport) of Na+, the transporter is a sodium-dependent glucose cotransporter (SGLT). This type of cotransport occurs in the epithelial cells of the intestine (see p. 87), renal tubules, and choroid plexus. [Note: The choroid plexus, part of the blood–brain barrier, also contains GLUT-1.]
V. GLYCOLYSIS REACTIONS
The conversion of glucose to pyruvate occurs in two stages (Fig. 8.11). The first five reactions of glycolysis correspond to an energy-investment phase in which the phosphorylated forms of intermediates are synthesized at the expense of ATP. The subsequent reactions of glycolysis constitute an energy-generation phase in which a net of two molecules of ATP are formed by substrate-level phosphorylation (see p. 102) per glucose molecule metabolized.
A. Glucose phosphorylation
Phosphorylated sugar molecules do not readily penetrate cell membranes because there are no specific transmembrane carriers for these compounds and because they are too polar to diffuse through the lipid core of membranes. Therefore, the irreversible phosphorylation of glucose (Fig.
8.12) effectively traps the sugar as cytosolic glucose 6-phosphate and commits it to further metabolism in the cell. Mammals have four isozymes (I–IV) of the enzyme hexokinase that catalyze the phosphorylation of glucose to glucose 6-phosphate.