On the meaning of effects of substrate structure on biological transport.

No single approach or simple combination of approaches will bring us an understanding of membrane transport, how it occurs, how it is driven and how it drives other processes. The particularity of the minds of individual investigators usually ensures that numerous attacks on a problem are undertaken, and also that these attacks are continued, and reapplied even after other investigators may have begun to deplore them. This article was in the first instance initiated for myself, to rethink what it is that my associates and I hope to achieve by one set of approaches, namely by observing the results of modifying the structure of substrates on their transport. To a degree I am taking a precaution that we do not decide that such studies are obsolescent, that the approach is indirect, a "black box" and born of a lack of courage for direct isolative approaches, or that only superficial objectives can be pursued by the approach, simply because superficial objectives are so often pursued by it. Perhaps it is enough to point out that even after isolation of a catalytic system or one of its components, much can be learned by looking for substrates t ha t it handles in unusual ways. Consider how well this statement applies to chymotrypsin. No doubt it also applies to the leucine-binding protein and other binder proteins. Such isolated proteins may also be "black boxes" to direct inspection. Perhaps it is a fragmentary rather than a universal truth that the information one gets by isolation is so unique as to deserve sole attention. On the contrary, each step of isolation appears to increase the advantage with which other methods of study can be applied. Having begun my analysis, I will proceed, however, to try to illustrate what this approach can do by examples (one in some detail) of what it is now doing, a