In The hitchhiker's guide to the galaxy a ship is hidden thanks to the "somebody else's problem" principle, namely people will ignore something problematic that isn't their problem. The reaction yield of enzymes is not something often discussed. The reason is pretty self evident: differentiating between low abundance products would be a minefield of pesky technical issues. So it is somebody else's problem.
Catalytic promiscuity on the same substrate
There are some cases where catalytic promiscuity on the same substrate is known, that is, there is a poor reaction yield. Mammalian serine racemase catalyses both racemisation and β-elimination. The balance depends on conditions, including ATP and divalent cations, rather than a universal 50% reaction yield; elimination can also help regulate D-serine levels, so it need not simply reflect a failure of selection. Another example are some sequiterpene synthases from plants and fungi, which convert a single compound farnesylpyrophosphate into a variety of different compound, a fraction of which are known to be bioactive —evolutionary plasticity plays a part, but that's a tangent for another time. In both cases, like most reactions, an unstable intermediate is formed which is forced in a direction that it would not spontaneously, but the enzyme residues do not always stop it. So a near-zero uncatalysed rate is surely a factor —but it is not the main factor.
Selection is surely a main factor. Low-turnover wasteful promiscuous activities are tolerated either because they are too small and/or their suppression would affect the main activity too much.
Enzyme evolution is never straightforward. In secondary metabolism suicide enzymes are sometimes found: even though the cellular cost of, say, a 200 aa enzyme is more than 200 ATP, not much product is needed, so that extravagant expenditure does not dent the cellular economy or is cheaper than having a series of extra enzymes. Less dramatically, in secondary metabolism there are several examples of enzyme reactions that, were I to design them with the standard cellular biochemical logic, I would adopt more, but straightforward, steps. Enzyme efficiency correlates with the requirement of the product, so these insanely complicated steps are kept because they do not need a high catalytic activity. So if I were to place a wager on what enzymes have the lowest reaction yield, I would place it on enzymes with low catalytic efficiency (≈low selection) and the most diabolical reaction (≈zero uncatalysed rate). Ironically, these enzyme are enzymes to avoided at all costs, so there is no sane way of knowing…
Enzyme evolution is never straightforward. In secondary metabolism suicide enzymes are sometimes found: even though the cellular cost of, say, a 200 aa enzyme is more than 200 ATP, not much product is needed, so that extravagant expenditure does not dent the cellular economy or is cheaper than having a series of extra enzymes. Less dramatically, in secondary metabolism there are several examples of enzyme reactions that, were I to design them with the standard cellular biochemical logic, I would adopt more, but straightforward, steps. Enzyme efficiency correlates with the requirement of the product, so these insanely complicated steps are kept because they do not need a high catalytic activity. So if I were to place a wager on what enzymes have the lowest reaction yield, I would place it on enzymes with low catalytic efficiency (≈low selection) and the most diabolical reaction (≈zero uncatalysed rate). Ironically, these enzyme are enzymes to avoided at all costs, so there is no sane way of knowing…
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