Energy Transfer from Adenosine Triphosphate

  • Published on

  • View

  • Download

Embed Size (px)


<ul><li><p>Energy Transfer from Adenosine Triphosphate</p><p>John Ross*Department of Chemistry, Stanford UniVersity, Stanford, California 94305</p><p>ReceiVed: October 5, 2005; In Final Form: February 14, 2006</p><p>We suggest a direct molecular mechanism of energy transfer from adenosine triphosphate (ATP) in hydrolysisand phosphorylation reactions, from chemical energy into mechanical energy. Upon hydrolysis of ATP, saybound to a protein, the electrostatic energy of Coulombic repulsion of the ions adenosine diphosphate andphosphate is available to assert a force on a neighboring molecular group in the protein and can do work onthat group, or as the ions recede from each without asserting such a force, they gain relative kinetic energy,which, in the absence of dissipative collisions that turn this kinetic energy into heat, can be converted intoany other form of energy and work by an impulse, a collision with a neighboring group, without restrictions.Either possibility can be used as a source of activation energy for reactions, as a source of energy to surmountenergy barriers in conformational changes, and as a source of work to be done, as in muscle. In some systemswhere the Gibbs free energy change is fully utilized, all of this energy is turned into mechanical energy, andwe suggest a similar mechanism. From the literature we cite some experimental evidence and several quotationsindicative of the possibility of our suggestion.</p><p>I. Introduction</p><p>Adenosine triphosphate, ATP, is an universal energy carrierin biological systems; it hydrolyzes and carries out manyphosphorylation reactions that proceed spontaneously. For thereaction</p><p>the standard Gibbs free energy change isG ) -31 kJ/molat pH 7 in the presence of magnesium at pMg) 3, and underphysiological conditions the Gibbs free energy change,G, isabout-50 kJ/mol.1</p><p>The free energy liberated in the hydrolysis of ATP isharnessed to drive reactions that require an input of free energy,such as muscle contraction. In turn, ATP is formed from ADPand HPO4-2 when fuel molecules are oxidized in chemotrophsor when light is trapped in phototrophs. This ATP-ADP cycleis the fundamental mode of energy exchange in biologicalsystems.1 Reactions of this type1 are ubiquitious: for metabo-lism, for pumping ions against chemical and electrical gradients,for generating conformational changes in proteins, etc.</p><p>The universality of the use of ATP is a marvel: what is itsbasis; how and why was ATP (and similarly GTP) selected forthis role; how is energy stored in ATP; how is energy transferredwhen ATP reacts?</p><p>Westheimer wrote an incisive article in 1978,2 addressingsome of these questions. We quote from his summary:</p><p>...the existence of a genetic material such as DNA requires acompound for a connecting link that is at least divalent. In orderthat the resulting material remain within a membrane, it shouldalways be charged, and therefore the linking unit should havea third ionizable group. The linkage is conveniently made byester bonds, but, in order that the ester be hydrolytically stable,that charge should be negative and should be physically close</p><p>to the ester groups. All of these conditions are met by phosphoricacid, and no other alternative is obvious. Furthermore, phos-phoric acid can form monoesters of organic compounds thatcan decompose by mechanisms other than nucleophilic attack,a mechanism that allows them sufficient reactivity in intermedi-ary metabolism... This remarkable combination of thermody-namic instability and kinetic stability was noted... by Lippmann.3</p><p>In this article we suggest a direct molecular mechanism ofenergy release and tranfer in hydration and phosphorylationreactions of ATP, from chemical energy into mechanical energy.The emphasis is first on the Coulombic repulsion between ADPand phosphate, and second, on the release of all the availableenergy in ATP. We know of no other prior suggestion on thisspecific topic.</p><p>II. Proposal for Molecular Energy Release from ATP inHydrolysis and Phosphorylation Reactions</p><p>The energy source in ATP has been described as due to ahigh energy bond and is so presented in standard texts. Thesource of the high energy has been assigned to Coulombicrepulsion of ADP and phosphate and to resonance effects.1</p><p>We gain some insight into the order of magnitude of theCoulombic repulsion in two very simple, separate ways. First,compareG of reaction 2, rewritten in greater detail, but withMg omitted with that of the hydrolysis of phosphoglycerate. In</p><p>reaction 3 there is only hydrolysis of a phosphorus-oxygen* Author to whom correspondence should be addressed. E-mail:</p><p></p><p>ATP-4 + H2O f ADP-3 + HPO4</p><p>-2 + H+ (1)</p><p>6987J. Phys. Chem. B2006,110,6987-6990</p><p>10.1021/jp0556862 CCC: $33.50 2006 American Chemical SocietyPublished on Web 03/16/2006</p></li><li><p>bond and no Coulombic repulsion of the post-hydrolysisproducts. In reaction 2 there is also hydrolysis of a phosphorus-oxygen bond followed by formation of relative kinetic energyin the reaction products due to reduction of Coulombic repulsion.As the two negative ions recede from each other to infiniteseparation we may estimate the (maximum) relative kineticenergy to be the difference in the standard Gibbs free energyof reaction 2,-31 kJ/mol, and that of reaction 3,-10 kJ/mol,which is about- 21 kJ/mol.1 A possible difference in resonanceenergy in these two reactions is ignored in this estimate.</p><p>A second estimate can be made with the most simpleelectrostatic calculation. The change in relative kinetic energy,K, of two ions A and B, of like charge with magnitudeszAandzB, with initial separationri and final separationrj is</p><p>where0 is the permittivity of free space, 8.85 10-12 F/m, is the relative permittivity of the medium, ande is the electroniccharge, 1.6 10-19 C. To calculate ranges of possible valuesof K, we need to choose ranges of the final separation andthe permittivity of the medium in which the hydrolysis of ATPtakes place. We take the initial separation to be 0.3 nm, whichis approximately the P-P distance in ATP, and the finalseparation to be 0.4 nm. The relative permittivity of water is78, and we estimate that the relative permittivity of a hydro-phobic environment, as in a protein fold, is 20.4 It could beconsiderably lower, perhaps 2-4. In Table 1 we list severalpossibilities, all for ) 20 and the distances indicated: Thefirst line combines the charge of the proton, in reaction 2, withthe charge of the phosphate; the second line neglects the chargeof the proton. The next two lines consider the presence ofdivalent Mg on ADP. Line 3 combines the charge of the protonwith that of the phosphate; line 4 neglects the charge of theproton. To obtain the values ofK for the relative permittivityof 10 (80), multiply the values ofK in the table by a factor of2 (divide by 4); to obtain the values for the case of the finalseparation distance at infinity, multiply the values in the tableby 4. For these ranges of conditions the entries in the table arewithin an order of magnitude of the first estimate of 21 kJ/mol.Thus the kinetic energy obtained from a reduction of theCoulombic repulsion is in the range of two-thirds of the standardGibbs free energy change of hydrolysis and in the range ofsomewhat less than half of the Gibbs free energy change underphysiological conditions.</p><p>The discussion presented here holds equally well for reactionsof ATP with pyrophosphate as one of the products.</p><p>An increase in ionic strength of the solution in which reaction2</p><p>occurs increases the shielding of the two negative ions and hencereduces the Coulombic repulsion. (This shielding produces theprimary salt effect in the kinetics of ions.)</p><p>As the HPO4-2 ion moves away from the ADP ion due toCoulombic repulsion, the relative kinetic energy of the two ions,in the absence of other interactions, increases. If ADP is held</p><p>in place, for example, by binding to a segment of an enzyme,then the HPO4-2 ion acquires all of this energy. If both ionsare free to move, then HPO4-2 acquires about 70% of therelative kinetic energy.</p><p>The essence of the present proposal is:Upon hydrolysis of ATP, the force due to the Coulombic</p><p>repulsion of the product ions can act on a neighboring moleculargroup in the protein and can do mechanical work on it bydisplacing it. If the ions recede from each other without assertingsuch a force, then they gain kinetic energy, which can, prior todissipation into heat, be transferred in an impulse, a collisionwith a neighboring group, into mechanical work. In either casethe mechanical energy generated can be wholly converted intoany other form of energy or work without any restrictions. IfATP is tightly bound to an enzyme, then upon hydrolysis the-phosphate may not be able to move away from ADP and theCoulomb repulsion is retained as potential energy until thebinding is reduced.</p><p>In some systems the Gibbs free energy change available fromthe reaction of ATP is fully utilized and all of this energy isturned into mechanical energy. This energy conversion occurslikely in the same way, due to the remaining electronic repulsion,as for that part due to the Coulombic repulsion.</p><p>For full conversion from chemical to mechanical energy nodissipation may occur. Dissipation may take place throughcollisions in which mechanical translational energy is changedto a statistical distribution, heat, or through various types ofinelastic collisions. Such events are precluded for very shorttime scales. For a relative kinetic energy of the phosphate of20 kJ/mol, for example, the phosphate ion moves about 0.1 nmin 0.3 ps. If no other collisions occur in that short time interval,as is likely, then the phosphate can transfer its kinetic energyto a neighboring molecular group and can thus achieve, say, aconformational change.</p><p>The mechanical energy being discussed, 20-50 kJ/mol, ison the order of 10-20 times thermal energy, 0.25 kJ/mol, andtherefore thermal fluctuations can be expected to have a minoreffect on the present argument.</p><p>More sophisticated calculations are of course possible, yetthe simplest calculations yield interesting concordant results.</p><p>III. Utilization of Mechanical Energy Obtained from ATP</p><p>The mechanical energy, generated from chemical energy inATP, in the products to be formed in the hydrolysis andphosphorylation reactions of ATP may serve different purposes.</p><p>First, the mechanical energy can produce work at themolecular level. Human inventions of the conversion of chemi-cal energy into work in a cyclic process require either a batteryconnected to a motor, or require the production of heat and itsusage in thermal engines, at reduced efficiency.</p><p>Second, the mechanical kinetic energy can be directly usedto surmount energy barriers on the reaction coordinate. Comparethis efficient conversion of electrostatic energy into mechanicalenergy, say, for surmounting a barrier or any other need forenergy, with providing a reaction complex, as in a unimolecularreaction, with thermal energy (heat). This thermal energy isgenerally distributed over all degrees of freedom statistically.A fluctuation has to occur to place sufficient energy into a givendegree of freedom, say, one bond, for reaction to occur. It takestime for such a fluctuation to take place, and hence thermalexcitation is less efficient (requires more energy and takeslonger) than activation by mechanical energy.</p><p>Third, the mechanical energy produced can be transferred tobring about a conformational change in the protein that requires</p><p>TABLE 1: Estimates of K, the Relative Kinetic Energya</p><p>zA zBK</p><p>(kJ/mol)</p><p>1. -3 -1 182. -3 -2 363. -1 -1 64. -1 -2 12</p><p>a The symbols are defined in the text.</p><p>K )zAzBe</p><p>2</p><p>40(1ri - 1rj) (4)</p><p>6988 J. Phys. Chem. B, Vol. 110, No. 13, 2006 Ross</p></li><li><p>energy input simply by the force exerted by the Coulombicrepulsion between ADP and phosphate on neighboring groupsin the enzyme.</p><p>Fourth, the repulsion between the negative ions, both inhydrolysis and in phosphorylation, enhances the rate of separa-tion of the products and thus leads to rapid completion of thereactions.</p><p>The suggestion made here for the conversion of chemicalinto mechanical energy can encompass several different sce-narios: (1) Suppose transfer of chemical energy occurs at agiven time, say, to effect a configurational change in the enzyme.There may be subsequent steps of configurational changesenergized by the first one. (2) The transfer of chemical energymay occur at different times. Suppose ATP is tightly bound toan enzyme as in actomycin; hydrolysis may take place, but the-phosphate cannot move away from ADP. In this case therecan be no reduction in the Coulombic repulsion and hence noconversion of that potential energy into mechanical work. Aftersome time interval the binding may be reduced, some reductionin the Coulomb repulsion may occur, and some mechanical workmay be done on neighboring groups. (3) Step 2 may occur morethan once, and thus energy from ATP may be distributed overseveral steps of the enzyme cycle.</p><p>All these advantages lead to the universal use of ATP as anenergy source in plants and animals.</p><p>IV. Possible Experimental Evidence for the PresentSuggestion</p><p>In this section we seek experimental indications for theutilization of the mechanical energy generated from the chemicalenergy available from ATP as suggested here. There is no proofof the suggestion, but the subsections list reasonable indicationsof its possibility.</p><p>A. Efficiency of Utilization of Energy from ATP. In manycases the energy available from ATP is not fully used; someenergy is dissipated. In other cases, however, the energyavailable from ATP is fully utilized.5,6 In the latter case it isclear that the mechanical energy generated from the repulsionof the product ions is also fully utilized, and the free energychange of the hydrolysis step is small. In refs 5 and 6 it wasshown that one ATP is utilized for each mechanical step inmyosin-V. The step size is 36 nm, and the maximum load is2.5 pN. The product of these numbers translates to 54 kJ/mol,well within experimental error of the full utilization of the Gibbsfree energy change of the hydrolysis of ATP under physiologicalconditions. Another example of full utilization, near 100%efficiency in ATP synthase, is given in ref 7.</p><p>The research described in refs 5 and 6 was done in vitro, inwater, which is likely a place for dissipation to occur due tothe collision of the phosphate ion with water molecules. Henceit is worthwhile noting that no measurable dissipation of themechanical energy takes place in these examples.</p><p>B. Crystal Structure of Monomeric Actin in the ATPState.8 The authors compare the crystal structures of the actinmonomer (G-actin) in the ATP and the ADP states... Acomparison of the structures in the two states reveals how therelease of the nucleotide-phosphate triggers a sequence ofevents that propagate into a loop to helix transition in the DNaseI-binding loop in subdomain 2.</p><p>C. The Role of MeH73 in Actin Polymerization and ATPHydrolysis.9 ...the imidazole of (Me)H73 does not make directcontact with the...</p></li></ul>


View more >