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The history of the "high-energy phosphates" and "high-energy phosphate bond" terms along with the squiggle bond and their connection with the flow of energy in biological systems, are outlined elsewhere in this Website. The role of these terms in fostering and maintaining the decades-old misconception of "exothermic bond breaking" are a primary focus of EXBAN. These terms, however, are not the sole semantic impediments to an understanding of bioenergetics, and of the molecular basis of energy changes in chemical reactions and physical processes in general. Other troublesome terms or phrases lend support to the misconception that the rupture of chemical bonds is accompanied by an energy release. Several of these are listed below.

"Cutting and Splicing"

    These are terms associated, in particular, with recombinant DNA technology and are therefore presently fashionable. The term "cutting" in this context refers to the hydrolysis of phosphodiester linkages in DNA or RNA, often at base-specific sites along the polymer chain. The single-strand breaks in the phosphodiester linkages that result from hydrolysis reactions catalyzed by restriction enzymes occur either at exactly opposite positions on the two strands to give rise to "blunt ends", or offset at specific palindromic sequences generating "sticky ends". These hydrolysis reactions are exothermic and spontaneous in the thermodynamic sense, as are hydrolysis reactions of nucleic acids and proteins in general. However, these hydrolysis reaction are catalyzed with appropriate enzymes, although RNA does undergo a slow hydrolysis in alkaline solution. The use of the shorthand term "cutting", while emphasizing the significant aspect of the reaction, i.e. breakage of the DNA strand, supports the widespread misconception that it is the bond breaking that produces the energy release. However, those students who have been convinced that bond breaking requires an input of energy, are likely to conclude, as evidenced by responses to exam questions, that the "cutting process" must be endothermic. The term "cutting" tends to disguise the hydrolytic nature of the reaction in which both bond making and breaking are occurring.

    It is in reality the reverse, the condensation or "splicing" reaction, in which the relatively-weak phosphodiester bond has to be formed following rupture of the stronger bonds at the ends of the 2 DNA stands, that is endothermic and endergonic. Emphasis only on the phosphodiester bond formation inherent in the term "splicing" suggests, erroneously again, that it is the bond formation that requires energy. Those students again, who know that bond formation is exothermic, are likely to conclude, again incorrectly, that the splicing reaction resulting in the phosphodiester linkage must therefore be exothermic. It would seem that students are "damned if they do and damned if they don't". In the same manner as with the overall synthesis of DNA and proteins, joining two DNA strands, or closing the nick with the "splicing reaction", is in fact endothermic and endergonic, i.e. it does not occur spontaneously. It must be pushed by coupling to a reaction that is spontaneous. The "splicing" reaction requires more than just DNA ligase as a catalyst for it to occur. The free energy of hydrolysis of the phosphoanhydride linkage of the NAD+ or ATP cofactor is required to drive the process. The manner in which this coupling can occur as viewed from a bond breaking and making perspective is considered in the "Bond Making and Breaking Tutorial".
    With reference to the discussion of sterol biosynthesis found in many texts Prof. Ray Fort finds that, perhaps with some sense of frustration, there is some "woofing and tweeting about energy-rich bonds". In his course website he points out that there is no such thing as an energy-rich bond and discusses the chemical basis of the Acetyl CoA as an acetyl transfer agent.


    This widely used term is analogous to "cutting ", but with a somewhat longer history, with both referring essentially to the same process. The term "cleavage" is, more often than not, employed in describing the result of a hydrolysis reaction. The term "hydrolytic cleavage", in this case, is also frequently encountered, and is less ambiguous.

"Energy Stored in Bonds"

    This phrase tends to be encountered in general chemistry texts but can be found in physical chemistry texts as well. It represents as with the other terms listed here, a convenient shorthand for a process that demands a more lengthy description to appreciate. Consider the following situation. A non-chemist interested in the environment and energy sources in the future, asks a chemist why hydrogen represents a good fuel. They understand that the molecule is simply composed of two hydrogen atoms bonded together, and want to know where the energy comes from. The response, without further elaboration, could well be that "the energy is stored in the bond". It is not difficult to imagine that the non-chemist would conclude that "if the energy is stored in the bond", then if there were no bond there would be no energy. It would seem entirely reasonable to conclude that energy release associated with hydrogen as a fuel must derive from breaking the bond. A distinctly clearer response would require that it be pointed out that good chemical fuels involve molecules in which the bonds holding them together are relatively weak, so that in reactions, e.g. involving oxygen (O2(g)), those weaker bonds are replaced by stronger ones in the products, water (H2O) in the case of the combustion of hydrogen.

    It is not difficult to understand why it is often suggested that students would be better off if left with their inconsistencies; i.e. to live with the convenient misconception that bond breaking is exothermic in their biology courses, but endothermic when dealing with problems in chemistry. There are, however, inconsistencies in this matter within biology itself. Retaining the misconception that the rupture of , e.g. the high-energy phosphate bond is exothermic, more often than not, it conceded that the rupture of H-bonding in the denaturation of DNA or the melting of ice, does requires an input of energy.



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