Exercise XVII 



PERMEABILITY AND ACTIVE TRANSPORT 87 



rate of diffusion is directly proportional to the 

 difference in concentration on the two sides of 

 the membrane. 



A third factor regulating the penetration of 

 substances through biological membranes is ac- 

 tive transport. This is of the highest importance, 

 and is the special subject of this week's experi- 

 ment. In active transport, a specific mechanism 

 exists, and work is done, to carry a substance 

 through a biological membrane. Specificity and 

 the expenditure of energy are the earmarks of 

 this process. Diffusion is an energy-yielding 

 process that can do work. Active transport is 

 an energy-demanding process; work must be 

 done upon it. Such active transport may take 

 substances from a higher to a lower concen- 

 tration, through a membrane that would other- 

 wise block their passage. What is much more 

 remarkable, active transport can take sub- 

 stances from a lower to a higher concentration, 

 that is, against the concentration gradient, bring- 

 ing them to many times the concentration they 

 possess in the medium from which they are being 

 absorbed. 



Active transport can be thought of as a process 

 of pumping. Little is know of the mechanism by 

 which it occurs. On the other hand, it is clear 

 that energy is required, and this is usually sup- 

 plied as ATP. The specificity of the process is 

 also apparent. Certain molecules may be passed 

 by the membrane and concentrated, while very 

 similar molecules are blocked. So, for example, 

 many cells are able to concentrate L-amino 

 acids, but not their "unnatural" D-amino acid 

 isomers. These distinctions are frequently rela- 

 tive rather than absolute; the specificity fre- 

 quently takes the form of a difference in rate of 

 transport. So, for example, galactose, glucose, 

 and fructose are all isomeric 6-carbon sugars 

 (C(5Hi206), all of about the same size and shape. 

 Yet a mammalian intestine absorbs galactose 

 more rapidly than glucose, and glucose more 

 rapidly than fructose. Similarly glucose pene- 

 trates the wall of the intestine much faster than 

 such a 5-carbon sugar as xylose or arabinose, 

 though the latter, being smaller, would diffuse 

 faster through a semipermeable membrane. On 



the death of the cells lining the lumen of the in- 

 testine, all such distinctions are lost. Now all the 

 hexoses penetrate at the same speed, and 5- 

 carbon sugars faster than 6-carbon sugars. 



We are going to study an example of the active 

 transport of glucose between two compartments 

 in the hamster: the inside or lumen of the small 

 intestine, and the "outside," normally filled by 

 the blood and lymph. 



The absorption of foodstuffs in mammals 

 takes place almost entirely in the small intestine. 

 The mucosa lining the intestine is thrown into 

 folds and ridges. Its surface is velvety with 

 numerous tiny, fingerlike projections, the villi; 

 and the individual cells lining the lumen have so- 

 called brush borders, tiny projections of cyto- 

 plasm upon their outer surface, so that this also 

 is velvety at another level of dimensions. All 

 these devices increase enormously the absorbing 

 surface of the intestine. In man it has been 

 estimated that the total intestinal area effective 

 for absorption is about 10 m^. Compare this 

 with the total area of skin, which is less than 

 2m2. 



After passing through the intestine, food sub- 

 stances are absorbed into the blood vessels or 

 lymph channels, and are transported first to the 

 liver and then to other tissues throughout the 

 body. The cells which cover the villi take an 

 active part in transferring some of these sub- 

 stances from the lumen of the intestine (the 

 mucosal side) to the outer space (the serosal side). 

 If the transfer of such a substance as glucose 

 were a matter of simple diffusion, the concentra- 

 tion on the serosal side would never become 

 greater than that on the mucosal side. In fact, 

 however, glucose is actively transported through 

 the intestine, so that it can become several times 

 more concentrated on the serosal than on the 

 mucosal side. 



The preparation and procedure we shall use 

 for studying the active transport of molecules 

 across the wall of the small intestine was devised 

 by Dr. T. H. Wilson of the Harvard Medical 

 School. The small intestine of the rat or ham- 

 ster is removed and cut into sections a few centi- 

 meters long. These sections are everted (turned 



