chairman's introduction 573 



ideal ; for (a) the process does not obey the kinetics of diffusion ; (h) while 

 any transport must involve motion of something from here to there, we 

 are still so ignorant of the mechanism that any emphasis on its resemblance 

 to diffusion may be prejudicial ; and (c) the term suggests a mechanism 

 very different from that of active transport, whereas it is quite conceivable 

 that the same "ferryboat" may be capable of either w^orking at active 

 transport or coasting along uncoupled from energy expenditure, depending 

 on the concentration of permeant. It might therefore be worth considering 

 a classification of specific transport into active transport and passive trans- 

 port; these terms seem as neutral as possible with respect to mechanism, 

 and they are clearly distinguished from non-specific permeability due to 

 direct diffusion (either through lipid or through an aqueous pore) rather 

 than to transport by some sort of carrier. 



What is the evidence for the existence of specific transport systems — 

 and of the corollary impermeability of a membrane to substances for which 

 such a system is lacking ? 



I. Crypticity 



With the discovery of more and more enzymes many cases have been 

 recognized, in all kinds of biological material, in which cells showed little 

 or no enzyme activity when intact but became active after mechanical 

 disruption or after chemical damage to the membrane (e.g. by toluene). 

 While this crypticity clearly suggested a permeability barrier, the evidence 

 was not rigorous; for the phenomenon could also conceivably be due to 

 the presence of the enzyme in the cell in a masked or inactive form. 



Late developments with bacteria produced one case in which the latter 

 alternative could be excluded. The well-known inability of many bacteria 

 to utilize citrate (or certain related members of the tricarboxylic acid 

 cycle) might be due to a permeability barrier or to absence of the required 

 enzymes. However, citrate was shown to be an obligatory intermediate in 

 the biosynthesis of glutamate from glucose in Aerobacter aerogenes [i]. 

 Since cells could be shown to be unable to utilize exogeneoiis citrate under 

 conditions where they must be rapidly metabolizing endogenous citrate, a 

 permeability barrier to citrate could be inferred [2].* 



* Reliance on studies with intact cells, combined with scepticism concerning 

 the possibility of a permeability barrier to citrate, was responsible for prolonged 

 doubt among many investigators concerning the existence of the tricarboxylic acid 

 cycle in microbes. In retrospect, indeed, it is rather ironical to find Professor Sir 

 Hans Krebs himself among this group [3]. Similar barriers did not interfere with 

 the recognition of the cycle in mammalian cells. Reconsidering this difference, one 

 is led to wonder whether bacteria, growing often in highly dilute environments, 

 might not need to retain tenaciously their intracellular pools of essential inter- 

 mediates (such as those of the tricarboxylic acid cycle), whereas the environment 

 of the mammalian cell might m.ake this requirement unnecessary. In a related 



