Energy Transfer Mechanisms in Mitochondria

The thesis is developed that an acceptable model of biological energy coupling must have universal application. The paired moving charge model of mitochondrial energy coupling is examined from the standpoint of this thesis. Fundamental to this model is the notion that energy coupling involves interaction between paired uncompensated charged species in two vectorially aligned and spatially separated reaction centers. The two charge-separating devices are assumed to be the electron transfer chain (in chloroplast and mitochondria) and intrinsic ionophores (in all transducing organelles and kinases). The universality of the ionophore principle becomes then the crucial test of the validity of the paired moving charge model. The multiple facets of ionophoremediated coupled processes are explored, e.g., coupled hydrolysis of ATP, hormonal control of ion movements, and active transport.The design and performance of living systems reflect to a profound degree two sets of principles-the principles of heredity and the principles of energy. The double helix principle of nucleic acid construction enunciated by Watson and Crick two decades ago (1) has been shown by overwhelming evidence to apply across the board to the hereditary process in all types of cells and in all forms of life. Moreover, all the events and systems that translate the hereditary process reflect with great fidelity both the centrality and the uniqueness of the double helix principle. The systems that execute replication (ribosomes, messenger RNA, transfer RNA, chromosomes, and the mitotic apparatus) and that control replication (genes, cistrons, and operons) are in fact molecular devices for the precise translation of the double helix principle. The point to be made is that, given a universal principle of heredity, then all the agents, systems, and tactics that underlie the execution of this principle must also be universal in nature. The ribosome and transfer RNA are two such examples in the structural domain. The mechanisms of protein and nucleic acid synthesis are examples in the functional domain. The universality of the genetic code is an example in the domain of molecular strategy.We have considered elsewhere the compelling nature of the case for the proposition that the principles of energy, like those of heredity, must be universal in character in biological systems (2, 3). We shall restrict our treatment of energy to the molecular tactics by which two processes are coupled one to another. Energy coupling subtends the most crucial aspects of energy in biological systems, and in our view, the understanding of all other aspects of energy, such as catalysis, is derivative from the fundamental principles of energy coupling. In the previous communication of this series, we have proposed and developed a model for mitochondrial energy coupling (4). Since the principles that underlie the model were arrived at by the fitting of theory and experiment, the ability of the model to rationalize mitochondrial energy coupling is in large measure a reflect...

Section: Universal Molecular Devices For Charge Separationmentioning

confidence: 99%

Paired moving charges in mitochondrial energy coupling. II. Universality of the principles for energy coupling in biological systems.

Green¹,

Reible²

1975

“…If one positions a negative ion at the center of coordinates, the probability density G(r) of finding the nearest positive ion between distances r and r + dr is G(r) = 47rr2p exp -47rp f x2e~/xdx}, [1] ra where p is the density of positive charges and [2 DkT [2] with e the magnitude of the ionic charge, D the dielectric constant, kT has its customary meaning, and a is the distance of nearest approach. The medium is assumed homogeneous and isotropic.…”

Section: Classification Of Charge Separationsmentioning

confidence: 99%

“…In the charge pair model presently under development (1)(2)(3)(4)(5) the pairing of opposite charges is the fundamental principle by which the operation of mitochondria and of other bioenergetic systems is rationalized. This pairing has so far been treated as a postulate.…”

Section: Introductionmentioning

confidence: 99%

“…For dielectric constants 10 or less pairing is absolute, for 20 there is some tendency towards pairing, and at 78 it is nonexistent. Pairing, partner exchange or charge substitution, inhibition, and antiport uncoupling can be rationalized within this framework.In the charge pair model presently under development (1)(2)(3)(4)(5) the pairing of opposite charges is the fundamental principle by which the operation of mitochondria and of other bioenergetic systems is rationalized. This pairing has so far been treated as a postulate.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Physical basis of charge pairing in mitochondria.

Kemény¹,

Singer²

1975

The postulate of charge pairing in the mitochondrial inner membrane is justified by applying a formula due to Fuoss to calculate the probability density for the distance between a positive and a negative charge. For dielectric constants 10 or less pairing is absolute, for 20 there is some tendency towards pairing, and at 78 it is nonexistent. Pairing, partner exchange or charge substitution, inhibition, and antiport uncoupling can be rationalized within this framework.In the charge pair model presently under development (1)(2)(3)(4)(5) the pairing of opposite charges is the fundamental principle by which the operation of mitochondria and of other bioenergetic systems is rationalized. This pairing has so far been treated as a postulate. Due to its fundamental significance it needs to be justified and its limitations must be explored.The distribution of all charges in and near the mitochondrial inner membrane is a problem of discouraging complexity unless some simplifying principle is recognized. The experimental techniques available in the field tend to focuson the electrons in the electron transfer chain. This point of view does not seem to lead to a successful theory. It was necessary to recognize that energy passes between two charges (6, 7), and that these charges are of-opposite sign (1). One of them can be the electron. Classification of charge separationsThere are two fields which have historically dealt with the distribution of charges from the point of view of our present interests. One is physical chemistry, as exemplified by the theory of catalysis (8), which deals with charge separations of the order of 1 A. The other one is the theory of electrolytes (9), which is valid for distances between charges larger than a few Angstroms, so that specifically quantum mechanical effects can be ignored. The medium here is characterized by a dielectric constant, which of course also means charge separation, but on a scale usually much smaller than 1 A. The charge separations of primary bioenergetic interest fall into the range of competence of the theory of electrolytes.The separation of ions in electrolytic solutions was investigated by Fuoss (9, 10). If one positions a negative ion at the center of coordinates, the probability density G(r) of finding the nearest positive ion between distances r and r + dr is G(r) = 47rr2p exp -47rp f x2e~/xdx}, In an electrolytic solution charges of both signs are free to move in three-dimensional space. The only restrictions arise from the mutual electrostatic interaction of the ions themselves and their distance of nearest approach a in Eq. [1]. This means that there is a competition between the energetic effect of the attractive Coulomb interaction favoring the nearest possible approach of opposite charges and the entropy effect favoring separations of the order of p -" due to the larger configurational volume available at larger separations. Low values of the dielectric constant make the Coulomb interaction dominant and charges tend to pair. High values of the dielec...

“…The charge pair model of bioenergetics (1)(2)(3)(4)(5) is based on the recognition of two basic features of bioenergetic systems: (i) separated opposite charges move in pairs, and (Hi) free energy, consisting of the interaction energy of the charges with each other and with the medium, is always at a local minimum apart from thermal fluctuations. These principles have been elaborated and fruitfully applied.…”

mentioning

confidence: 99%

Charge pair model of bioenergetics: redox enzymes.

Kemény¹,

Mahanti²

1976

A model of electron transfer between redox enzymes is constructed on the assumption that the apoenzyme contains orientable units, which are tentatively identified with flipping amino acids. The model is based on the entatic state hypothesis, and the rate of electron transfer is derived.The charge pair model of bioenergetics (1-5) is based on the recognition of two basic features of bioenergetic systems: (i) separated opposite charges move in pairs, and (Hi) free energy, consisting of the interaction energy of the charges with each other and with the medium, is always at a local minimum apart from thermal fluctuations. These principles have been elaborated and fruitfully applied. This paper is concerned with the further development of the theory, as applied to oxidative phosphorylation.Oxidative phosphorylation is a process consisting of a very large number of steps if all chemical reactions and charge motions are considered. It is a conservative process, although its efficiency has not been reliably determined (6-7). We would expect each step to be carefully designed to avoid unnecessary loss of free energy. The only way to avoid losses completely is by blocking all reactions. A certain amount of loss must be designed into the system, since the purpose is to convert the free energy of substrate into the free energy of ATP. Here we will consider a fundamentally conservative design and ignore losses as a first approximation.Let us consider the magnitude of the free energies and activation free energies involved. Since the activation energies are often only a few RT (R is the gas constant; T, the absolute temperature) (8, 9), none of the steps should necessarily involve large energy barriers. If they do, they probably have to be attributed not to electron transfer but to other processes. The free energy transferred from a single electron to Mg++Pi-or Mg++ADP-on each crossing of the membrane is approximately 7.5 kcal/mol. This transfer is probably broken down into several steps, although a single step transferring all the energy at once would do in principle. Energies of reactions in general could easily be higher than this last value, and special devices must be available to keep energies and activation energies of all reactions within the above bounds. These devices are the electron transfer chain and the ionophoric complexes. How do they perform their tasks? This paper deals with the redox enzymes of the electron transfer chain. Part 2 continues with electron transfer and includes discussion of ionophoric complexes.The presence or absence of the electron can be readily de- (Fig. 1). The intersections fall between the oxidized and reduced equilibrium coordinates (11,12). In the initial state the solid lines apply; in the final state the broken ones do. We assume all parabolas have the same curvature. Electron transfer has to conserve energy and the transitions are vertical. Consequently, transfer is possible only if xi and x2 are momentarily such that the vertical lines connecting the two parabolas on ea...