ANALOG INHIBITION OF MEMBRANE TRANSPORT 267 



distinguished from possible inhibitions of amino acid incorporation in the 

 cell. Reference should be made to the very complete investigation of amino 

 acid transport in brain slices by Abadom and Scholefield (1962), in which the 

 many competitive inhibitions established point to several separate amino 

 acid transport systems. 



The entrance of valine, proline, and hydroxyproline into the human 

 erythrocyte is not mutually competitive, but is inhibited markedly by 

 certain sugars, such as glucose, galactose, and xylose, although not by 

 fructose (Rieser, 1961). These results would indicate that some amino acids 

 and sugars follow the same transport pathway. If this is a general phenome- 

 non, one must consider in the use of analogs of these substances the possi- 

 bility that an amino acid analog might depress glucose uptake, and thereby 

 secondarily interfere with the transport by suppressing energy generation. 



The accumulation of L-histidine by the parasitic fungus Botnjtis fabae 

 is inhibited by most other amino acids, and one transport system seems to 

 be available to all the amino acids (Jones, 1963). Substitution at the NH2 

 or COOH groups lessens or abolishes the inhibitory activity, indicating 

 that the binding to the carrier is at least partly electrostatic. 



Miscellaneous Transport Systems 



The oxidation of protocatechuate by a Flavohacterium is competitively 

 inhibited by ^-aminosalicylate and one might conclude that mutual in- 

 teraction with some enzyme is responsible. However, 59-aminosalicylate 

 does not affect the rate or extent of the oxidation in extracts, measured in 

 different ways (Hubbard and Durham, 1961). These results thus point to 

 competition for a transport system in the membrane, rather than the more 

 usual explanation. The active transport of biotin across the hamster in- 

 testine is inhibited by various analogs (e.g., biocytin, desthiobiotin, di- 

 aminobiotin, and biotin methyl ester), but the nature of the inhibition was 

 not investigated so it may not be competitive (it is not with lipoate) (Spen- 

 cer and Brody, 1964). The active influx of urate into erythrocytes is com- 

 petitively inhibited by hypoxanthine with K^ = 0.1 mM, whereas the 

 efilux consists of two components, one sensitive to hypoxanthine (Lassen 

 and Overgaard-Hansen, 1962). 



There are several instances in which the transport of inorganic ions is 

 inhibited by other related ions. The transfer and exchange of phosphate 

 across the membrane of S. aureus are inhibited by chlorate, borate, and ar- 

 senate (Mitchell, 1954), although only arsenate is able to substitute com- 

 pletely for phosphate in the exchange. The uptake of sulfate by yeast is 

 competitively inhibited by thiosulfate (Kleinzeller et al., 1959). Nitrate 

 inhibits quite well the accumulation of iodide in the rabbit ciliary body, 

 50% reduction of the tissue/medium ratio occurring at 3 vaM, but it is 

 not known if this is truly competitive (Becker, 1961). 



