Characteristics of glucose transporters (uniporters)
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| Figure 7.5 Comparison of the transport kinetics of facilitated diffusion and simple diffusion. The rate of transport of substrate is plotted against the concentration of substrate in the extracellular medium. In common with enzyme catalysis, transporter-catalyzed uptake has a maximum transport rate, Tmax (saturable). Kt is the concentration at which the rate of substrate uptake is half maximal. For simple diffusion, the transport rate is slower and directly proportional to substrate concentration. |
| MEMBRANE ANCHORING PROTEINS |
| Lateral movements of some membrane proteins are restricted by their tethering to macromolecular assemblies inside (cytoskeleton) and/or outside (extracellular matrix) the cell, and, in some cases, to membrane proteins of adjacent cells, e.g. in tight junctions between epithelial cells. Lateral diffusion of erythrocyte integral membrane proteins, band 3 (Cl-/HCO3- antiporter) and glycophorin, is limited by indirect interaction with spectrin, a cytoskeletal protein, through ankyrin and band 4.1, respectively. Such interactions are so strong that they limit lateral diffusion of band 3. Hereditary spherocytosis and elliptocytosis are human diseases caused by genetic defects of spectrin. Ankyrin mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Deficiency of ankyrin also affects the intracellular targeting of Na+/K+-ATPase and Na+/ Ca2+ antiporter in cardiac muscle cells (see Fig. 7.6), resulting in the elevation of intracellular Ca2+ which triggers an arrhythmia. The intracellular targeting of Na+/K+-ATPase in kidney is inhibited by the mutation of the γ-subunit of this ATPase. The defect is implicated in renal hypomagnesaemia. |
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| FORMATION OF ANTIBODIES TO PHOSPHOLIPIDS |
| A 54-year-old woman was admitted to the hospital because of acute renal failure and thrombocytopenia. The patient had been in excellent health until 5 weeks earlier, when she began to have respiratory symptoms with fever that was unresponsive to antibiotics. Examination of the renal biopsy specimen revealed abnormalities in all components of the cortex, defining the membranoproliferative pattern of glomerular injury. |
| Comment. Among the conditions associated with the glomerular injury, a thrombotic angiopathy was considered, and then finally the antiphospholipid antibody syndrome was favored, since titer of anti-cardiolipin antibody was elevated. The antiphospholipid antibody syndrome was initially diagnosed on the basis of recurrent arterial and venous thrombosis leading to stroke and myocardial infarction, recurrent spontaneous abortions and fetal wastage, thrombocytopenia, and various neurologic manifestations. These antibodies are also found in systemic lupus erythematosus. |
| Glucose transporters are essential for facilitated diffusion of glucose into cells. The glucose transporter family comprises five major species, named GLUT-1 to GLUT-5 (Table 7.4). They are transmembrane proteins similar in size, all having about 500 amino acid residues and 12 transmembrane helices. GLUT-1, in red blood cells, has a Km of ∼2 mmol/L; most of the GLUT-1 molecules are active under fasting conditions (glucose concentration of 5 mmol/L; 90 mg/dL). In contrast, pancreatic islet β-cells express GLUT-2, with a Km of more than 10 mmol/L (180 mg/dL). In response to the intake of food and resulting increase in blood glucose concentration,
GLUT-2 molecules mediate an increase in the cellular uptake of glucose, leading to insulin secretion (see Chapter 20). Cells in insulin-sensitive tissues such as muscle and adipose have GLUT-4. Insulin stimulates translocation of GLUT-4 from intracellular vesicles to the plasma membrane, facilitating glucose uptake during meals.
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