SPECIFICITY OF TRANSPORT 



proposed to occur by means of the action of a niutarotase (Keston, 

 1954). This possibility was excluded by showing that the intestinal 

 monosaccharide system transports the cyclic ether, 1-dcoxyglucose, 

 which is of course not subject to mutarotation (Crane and Krane, 

 1956). 



Inhibitors not recognized to be transported may also assist in 

 describing the site. Phloretin, the aglycone of phlorizin, inhibits the 

 glucose transport system of human erythrocytes at least 50 times 

 as strongly as phlorizin does. Phloretin, the free diphenol, is com- 

 petitive in its action; both phenolic groups are necessary, and com- 

 parison of analogs has indicated that the magnitude of the spatial 

 separation of these two hydroxyl groups is important. Accordingly, 

 this distance may be an important parameter in the description of 

 the monosaccharide transport site. Phloretin, as well as stilbestrol and 

 other potent analogs of phloretin are, to complicate investigation, 

 fixed by red blood cells at sites far more abundant than the transport 

 sites (LeFevre and Marshall, 1959). 



In contrast, it is phlorizin, the glycoside, that inhibits monosac- 

 charide transport in the intestine and the kidney, and its entry into 

 Ehrlich ascites tumor cells. Alvarado and Crane (1962) find phlori- 

 zin a competitive inhibitor for sugar transport into intestinal strips, 

 phloretin being less than 1 per cent as active as the glycoside. 



Findings on transport systems for organic anions in the kidney 

 and in the diaphragm, and on transport systems for organic cations, 

 could also be selected for a similar complementary consideration of 

 the nature and function of the transport sites concerned. Similarly, 

 the anions (thiocyanate, perchlorate, periodate, iodate, chlorate, 

 hypochlorite, nitrate, nitrite, bromate, and numerous others) com- 

 peting with iodide for transport by the thyroid, gastric, and salivary 

 glands form an interesting series. Divalent cation transports (e.g., 

 of sulfate by the kidney) are also known. Limited explorations have 

 been made of the effect of structure on purine transport. 



In summary, we may say that the transport of amino acids and 

 sugars by their respective transport-mediating sites appears to occur 

 for a wider range of molecular structures than can be handled by 

 most enzymatic reactions. The patterns of specificity are sufficiently 

 unlike those of most enzymes, suggesting that ordinary known en- 

 zymes in special locations are usually not the mediators of transport. 



In this connection we should remember that transport also 

 discriminates between solutes (e.g., the alkali metal ions) not sub- 



69 



