EFFECTS ON PERMEABILITY AND ACTIVE TRANSPORT 913 



PM/g cells and by 4.7 //moles Hg++/g cells. The inhibition-concentration 

 curves are said to conform to the equation ^ = (I) (1 — i)ji and hence to 

 suggest reaction of the mercurial with a phosphate carrier X, according to 

 I + X :±5: IX.* This equation is simply that for noncompetitive inhibition 

 and it is difficult to understand how it would serve to indicate any partic- 

 ular mechanism by which transport is depressed. Mitchell then proceeds 

 to calculate the number of carrier molecules for 100 molecules of intra- 

 cellular phosphate; since the cells contained 147 //moles P,/g cells, 1.5 and 

 3.2 molecules of PM and Hg++, respectively, are required for 50% inhibition 

 per 100 molecules of internal P^. It was apparently assumed that if 50% 

 inhibition is given by these numbers of molecules, 100% inhibition would 

 be given by twice these, namely, 3.0 and 6.4 molecules of PM and Hg++, 

 respectively. If this were true titration or zone C inhibition, this would be 

 correct, but inspection of the curves shows that it is not; indeed, it is evi- 

 dent that approximately 20 and 40 //moles/g cells of PM and Hg++ are 

 needed for 90% inhibition (curves do not reach complete inhibition, which 

 would require appreciably more of the mercurials). Therefore, his conclusion 

 that the number of carriers is not more than 3% of the internal P, is not 

 valid. In addition, the mercurials must be bound to cell components other 

 than a hypothetical carrier, so that under any circumstances it would be 

 difficult to estimate the relative amount of carrier present, just as it is 

 impossible to calculate the amount of an enzyme present in a complex 

 mixture by the quantity of mercurial required for 50% inhibition. 



Transmembrane and Transcellular Transports 



The uptake of a substance into a cell is often a process different from 

 the transport across a layer of the cells. If a substance is moved against 

 a concentration gradient from one medium into a similar medium, it is 

 an active transport, whereas accumulation of a substance within a cell can 

 be the result of binding. A good example of this is the transport of triiodo- 

 thyroacetate by rat intestine (Herz et al., 1961). The mucosal -^ serosal 

 transport is inhibited 93% by 1 raM Hg++, but the accumulation in the 

 tissue is actually accelerated 16%. The cellular uptake was postulated to 

 be due mainly to binding. The accumulation of Fe+++ (Saltman et al, 1955) 

 and Cu++ (Saltman et al., 1959) by rat liver slices is slightly stimulated by 

 p-MB, and it is very likely that these are instances of binding to intracel- 

 lular ligands. There is sometimes not so clear a separation of transmembrane 

 and transcellular transports. Rat intestinal slices accumulate Ca++ to a tis- 



* Mitchell gives the equation as ^ = (I)i7(l — i), changing his symbols to those 

 used in the present work, which is obviously incorrect, since it would mean that the 

 inhibition would vary inversely with the inhibitor concentration, so I have taken the 

 liberty of rewriting it. 



