Living on a Knife Edge

Charles Darwin, The Variation of Animals and Plants under Domestication (1868) 

This is a state similar to what you can observe in a river in calm conditions although water is constantly being supplied from above, it is flowing away at exactly the same rate, with the result that not only does the flow rate remain 

As a specific example, let us consider the human disease phenylketonuria, which is caused by the lack of an essential enzyme, phenylalanine 4-monooxygenase. I shall return to this in the next chapter, and for the moment it is sufficient to say that people who lack the enzyme completely have the disease, but people who have only half of the normal amount of enzyme have no related health problems at aU half the normal amount of enzyme appears to be just as good as the full amount. How can this be If they have half the normal amount of enzyme (as they do, in this and other similar cases), then the reaction the enzyme catalyzes should proceed half as fast, and ought this not have at least some effect If not, does this not mean that normal individuals have at least twice as much of the enzyme as they need, and that the human species could evolve to become more efficient by decreasing the amount they make, thereby releasing precious resources for other purposes  

This happens to be an example that has been very thoroughly studied in the human species, as phenylketonuria is a serious disease that is easily diagnosed 

The answer turns ont to be one of mathematical necessity, and explaining it will require some care. There are two biochemical points to consider at the outset. In the first place, most metabolic systems spend a large amonnt of their time in steady states, and we can go some way toward nnderstanding how biochemical systems behave by restricting the discnssion to steady states. In doing this, however, we should keep in mind that it is only a beginning, because many of the most interesting moments in the life of a cell involve transitions from one steady state to another. 

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The conclusion from all of this is that we do not live on a knife edge. We do not need natural selection to explain the observation that much of metabolism can be represented simply as a set of pools of major metabolites at approximately constant concentrations, with chemical flows between them that proceed at rates that over short timescales vary little or not at all. Systems of enzymes catalyzing diverse sets of reactions readily achieve steady states because that is almost an automatic property of such systems. Assigning kinetic properties haphazardly to all the enzymes in a system normally does not produce any exotic properties for the whole system as Kacser and Bums remarked three decades ago, almost any set of enzymes will generate a steady state with all fluxes in operation, with intermediate pools at their proper levels, and so on. So, desirable as these properties may be, we have no need to invoke natural selection to explain them. 

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