Oxygen Is the High-Energy Molecule Powering Complex Multicellular Life: Fundamental Corrections to Traditional Bioenergetics.

Klaus Schmidt-Rohr

doi:10.1021/acsomega.9b03352

Abstract

A fundamental re-assessment of the overall energetics of biochemical electron transfer chains and cycles is presented, highlighting the crucial role of the highest-energy molecule involved, O2. The chemical energy utilized by most complex multicellular organisms is not predominantly stored in glucose or fat, but rather in O2 with its relatively weak (i.e., high-energy) double bond. Accordingly, reactions of O2 with organic molecules are highly exergonic, while other reactions of glucose, fat, NAD(P)H, or ubiquinol (QH2) are not, as demonstrated in anaerobic respiration with its meager energy output. The notion that “reduced molecules” such as alkanes or fatty acids are energy-rich is shown to be incorrect; they only unlock the energy of more O2, compared to O-containing molecules of similar mass. Glucose contains a moderate amount of chemical energy per bond (<20% compared to O2), as confirmed by the relatively small energy output in glycolysis and the Krebs cycle converting glucose to CO2 and NADH. Only in the “terminal” aerobic respiration reaction with O2 does a large free energy change occur due to the release of oxygen’s stored chemical energy. The actual reaction of O2 in complex IV of the inner mitochondrial membrane does not even involve any organic fuel molecule and yet releases >1 MJ when 6 mol of O2 reacts. The traditional presentation that relegated O2 to the role of a low-energy terminal acceptor for depleted electrons has not explained these salient observations and must be abandoned. Its central notion that electrons release energy because they move from a high-energy donor to a low-energy acceptor is demonstrably false. The energies of (at least) two donor and two acceptor species come into play, and the low “terminal” negative reduction potential in aerobic respiration can be attributed to the unusually high energy of O2, the crucial reactant. This is confirmed by comparison with the corresponding half-reaction without O2, which is endergonic. In addition, the electrons are mostly not accepted by oxygen but by hydrogen. Redox energy transfer and release diagrams are introduced to provide a superior representation of the energetics of the various species in coupled half-reactions. Electron transport by movement of reduced molecules in the electron transfer chain is shown to run counter to the energy flow, which is carried by oxidized species. O2, rather than glucose, NAD(P)H, or ATP, is the molecule that provides the most energy to animals and plants and is crucial for sustaining large complex life forms. The analysis also highlights a significant discrepancy in the proposed energetics of reactions of aerobic respiration, which should be re-evaluated.

Highlights

Bioenergetics is an important area of biochemistry, accounting for the energy driving biochemical reactions.[1−8] While it is known, in principle, that only reactions with molecular oxygen provide enough energy to make large complex organisms viable,[9] biochemistry and biology textbooks assume without proof that biochemical energy is stored in fuel molecules such as glucose.[1−5,8,10,11] In this paper, we demonstrate that this view is incorrect since most of the energy is derived from O2 with its relatively weak double bond.[12]
Textbooks describe biochemical energetics at three main levels: (i) Conceptual overviews of bioenergetics show naıve statements and diagrams about sunlight and nutrients providing the energy organisms need,[1,2,8] and it is assumed without reflection that organic fuel molecules contain the energy released in aerobic respiration.[3−5,11] (ii) In more specific summaries of respiration and photosynthesis reactions, the Gibbs free energy changes ΔrGo′ in overall reactions, such as NADH + H+ + 1/2O2 → H2O + NAD+, are given but without meaningful explanation
We have provided an intuitive and quantitative description of biochemical energetics based on chemical energy stored mostly in weak bonds, showing that O2 with its relatively weak double bond is the molecule with the highest energy per bond in biochemistry

Summary

■ INTRODUCTION

Bioenergetics is an important area of biochemistry, accounting for the energy driving biochemical reactions.[1−8] While it is known, in principle, that only reactions with molecular oxygen provide enough energy to make large complex organisms viable,[9] biochemistry and biology textbooks assume without proof that biochemical energy is stored in fuel molecules such as glucose.[1−5,8,10,11] In this paper, we demonstrate that this view is incorrect since most of the energy is derived from O2 with its relatively weak double bond.[12]. Reactions of fuel molecules in the absence of O2 are not strongly exergonic, even when a strongly bonded molecule such as CO2 is formed: C6H12O6 + 2NAD+ → 2CH3(C O)COO−(pyruvate) + 2NADH + 4H+ ΔrGo′ = −147 kJ/mol, ΔrGo′′ = −153 kJ/mol (3a). It is apparent from these examples and others given below that emnoerregy,O122,17i−n21 the reaction results in the release almost regardless of the nature of of more the fuel molecules or reaction products. The obvious interpretation of these observations is that a lot of chemical energy resides in O2.12,20,21 We had previously shown, through a generalized bond-energy analysis, that 418 kJ of heat is released per mole of O2 in the combustion of organic molecules.[12] The excellent agreement of this analysis with the experimental data has convincingly documented its validity.[12]. Recognizing O2 as the crucial high-energy molecule highlights discrepancies between free energy release and claimed ATP production in different reactions of aerobic respiration

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES