Transport of Glucose Through the Cell Membrane
Before glucose can be used by the body’s tissue cells, it must be transported through the tissue cell membrane into the cellular cytoplasm. However, glucose cannoteasily diffuse through the pores of the cell membranebecause the maximum molecular weight of particles that can diffuse readily is about 100, and glucose has a molecular weight of 180. Yet glucose does pass to the interior of the cells with a reasonable degree of freedom by the mechanism of facilitated diffusion. Basi-cally, they are the following. Penetrating through the lipid matrix of the cell membrane are large numbers of protein carrier molecules that can bind with glucose. In this bound form, the glucose can be transported by the carrier from one side of the membrane to the other side and then released. Therefore, if the concentration of glucose is greater on one side of the membrane than on the other side, more glucose will be transported from the high-concentration area to the low-concentration area than in the opposite direction.
The transport of glucose through the membranes of most tissue cells is quite different from that which occurs through the gastrointestinal membrane or through the epithelium of the renal tubules. In both these cases, the glucose is transported by the mechanism of active sodium-glucose co-transport, in which active transport of sodium provides energy for absorbing glucose against a concentration difference. This sodium co-transport mechanism functions only in certain special epithelial cells that are specifically adapted for active absorption of glucose. At other cell membranes, glucose is transported only from higher concentration toward lower concentration by facilitated diffusion, made possible by the special binding properties of mem-brane glucose carrier protein.
The rate of glucose transport as well as transport of some other monosaccharides is greatly increased by insulin. When large amounts of insulin are secreted by the pancreas, the rate of glucose transport into most cells increases to 10 or more times the rate of transport when no insulin is secreted. Conversely, the amounts of glucose that can diffuse to the insides of most cells of the body in the absence of insulin, with the exception of liver and brain cells, are far too little to supply the amount of glucose normally required for energy metab-olism.
In effect, the rate of carbohydrate utilization by most cells is controlled by the rate of insulin secretion from the pancreas.
Immediately on entry into the cells, glucose combines with a phosphate radical in accordance with the following reaction:
This phosphorylation is promoted mainly by the enzyme glucokinase in the liver and by hexokinase in most other cells. The phosphorylation of glucose is almost completely irreversible except in the liver cells, the renal tubular epithelial cells, and the intestinal epithelial cells; in these cells, another enzyme, glucosephosphatase, is also available, and when this is activated,it can reverse the reaction. In most tissues of the body, phosphorylation serves to capture the glucose in the cell. That is, because of its almost instantaneous binding with phosphate, the glucose will not diffuse back out, except from those special cells, especially liver cells, that have phosphatase.