Energetics of Polymerization: A Contrlbutlon to an Understandlna" of Proteln Svnthesls To the Editor
I wish to point out inconsistencies in the article "Energetics of Polvmerization" bv Herbert C. Friedman which aDpeared in-the August 1986 edition of this Journal. What I particularlv disaaree with is the notion that "the energetics of o ~ d e r e d - ~ r o t & synthesis requires the utilization. . .of the equivalent of four 'high-energy' phosphate bonds so that mechanistically a system had to be elaborated that satisfied these pre-existing requirements." Friedman suggests-that protein synthesis requires more energy than polynucleic acid synthesis because of the necessitv of selectine one out of 20 amino acids versus one out of oniy four nucfeotides. I t seems to me that, a priori, the amount of ordering demanded in selectine amino acids is rather small and requires little energy. If s"=R In W where W = 1/20 then S = 6 cal/dea mole and TS (at 298 K) = 1.8 Kcal/mole. Less than the en& in one "high-energy" phosphate bond. Further, the amount of ordering required to select amino acids for gramicidin S is the same as for large proteins, but its synthesis actually uses half the phosphate bond energy used for large protein synthesis (per amino acid residue). One should beware of assuming that living organisms are maximally efficient. Evolutionary change proceeds by chance and "jury-rigging" new systems out of available parts. Final configurations are often more complex and less efficient than would he so for systems engineered from scratch. If the ordering problem is a maior factor in the enerev requirements of protein synthesis then perhaps it has somethin2 to do with the complexities of translation between nuccic acid and peptide polymers. But this is not a priori required of living systems, and i t is misleading to say that this much energy had to be required for protein synthesis. Jay Splvack Biological and Physical Science State University of New Y o h Agricultural and Technical College Cobleskill. NY
To the Editor
Spivack's line of thinking runs like this: The argument that protein synthesis is "expensive" merely means that i t is inefficient, a result of chance happenings that one really should not try to interpret; the expense has nothing to do with the circumstance that apart ofthis process is cokerned withselectionout of a large poolof different amino acids, but it has to do with the fact that we happen to be dealing with a complex or complicated process. I would like to submit that the comnlexitv of nrotein svnthesis is wreciselv a consequence df the fact that selection is a necessary a i d integral part of the process. As I tried tomakeabundantly clear in my article, the details of the complexities of protein synthesis are. from the viewooint of evolution, in part arbitrarv. One c o d d invent, if one were clever enough, an alternate system serving the same ends, but the energetics are necessarily
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independent of that end. It is biologically somewhat unsatisfactory to say that enerm expenditure is s i m ~ l av functionand an incidental function to b o o G o f org&fzational complexity, that is, of purely mechanistic complications; this view completely ignores any possihle functiunnl grounds for .that complexity. The fact that rhe individual reactions of protein synthesis cannot be precisely nailed down as to their energetic correlates simply follows from the difficulties of measuring the eneraetics of these reactions. This was the point ofthe paper. ~ i f i i r u l t i eincarryingout i measurements should not hlind one to (1) the predirtahle outcome that these measurements,once they are made, will haw toadd up to the observed orwall energy expenditure, and (2) the functional correlates of such measurements. As to thecalculation uf theenergy necessary toachieve the selection of one particular amino acid from a mixture of 20, the equation proposed hy Spivack dues not take into consideration the selectivity required for the synthesis of proteins. In fact, the higher theselectivity of the process, the higher its entrodc cost. One can areue that if a svstem had ivolved that would have required &en more energy expenditure, the selectivity associated with protein synthesis would have been even higher; i. e., the error-frequency would have been less. While the synthesis of gramicidin S can afford a low selectivity since there are only 10 peptide bonds formed in the process, the manufacture of a protein of say 1000 amino acids would result in negligible yields if sucha low selectivity were used. Thus, in fact, the example of gramicidin S further supports the point I tried to make in the paper. Perhaps a difficulty in understanding the correlation between energy expenditure and selectivity lies in the circumstance that-in accord with old-established principles of coupled reactions-energy expenditure has to take place within or in association with the individual steps whose agareaate -- . result is protein svnthesis. but that the rationale for such energy exienditurLlies in the process of selectivity that is not immediately obvious when the energetics of the individual steps as such are considered. Precisely the same argument holds for the energetics of ordered RNA or ordered DNA formation, since the recognition of the ordering process as such, although a necessary part of the process, is not as obviously apparent as the fact that a certain amount of energy is actually expended. Spivack's approach to protein synthesis emphasizes the lack of maximal efficiency of living organisms. I t stresses " 'jury-rigging' (of) new systems out of available parts", and i t insists that "final configurations" are not "engineered from scratch". This attitude toward efficiency and toward raw materials is not unknown to biologists when considering living systems a t the oraanismic level. Thus. for examnle. in adiscussion on orchids,stephen ~ a ~yo u l (in d "The panda's Thumb") says "they are jury-rigged from a limited set of available components", that they were "not made by an ideal engineer" and that one finds here "a collection of parts generally fashioned for other purposes". I would like to submit that generalizations made at the organismic level should not be transferred unquestioningly to events and functions a t the molecular level. Herbert C. Frledmann Deparlment of Biochemistry and Molecular Biology The University ot Chicago 920 East 58th St. Chicago, IL 60637
