Rich 1984 Biochim Biophys Acta

From Bioblast
Jump to navigation Jump to search
Publications in the MiPMap
Rich PR (1984) Electron and proton transfers through quinones and cytochrome bc complexes. Biochim Biophys Acta 768:53-79.

» PMID: 6322844

Rich Peter R (1984) Biochim Biophys Acta

Abstract: It is the aim of this article to discuss the details of electron and proton transfers through quinones and cytochrome bc complexes. Emphasis will be placed on the molecular organisation and mobility of components, on the chemistry of the individual redox steps, and on the relation of these factors to overall protonmotive ability.

Bioblast editor: Gnaiger E

Selected quotes

  • "Solid state" and "liquid state" as extremes of molecular organisation: The biological electron transfer chains consist of a number of large multiprotein complexes which generally span the lipid bilayer membranes in which they are situated. They are often connected to each other electronically by smaller components, which may be located in the membrane or in the aqueous phase. A specific example of the interaction of succinate dehydrogenase and NADH dehydrogenase with the bc1 complex in mitochondria will be used for discussion. It is known that quinone plays a role as the electronic connector. Two extreme types of molecular organisation may be envisaged, which may loosely be termed 'liquid state' and 'solid state' (Figs. 1A and B) [19,20]. In a liquid-state system, one or all components are freely diffusing and hence randomly arranged in the membrane as a two-dimensional solution. Such a notion was originally applied to the quinone pool of mitochondria by Green [21] and by Kröger and Klingenberg [22]. Interactions occur by collisional processes and long-lived intermediates are not readily observed, since electron transfer is rapid after an appropriate complex has been formed [23]. The system will be rate-limited by diffusional processes and an increase in reactant concentrations will produce an increased rate. In an ideal solution, a quinol produced by a given dehydrogenase is potentially able to interact with a large number of cytochrome bc1 complexes within its expected lifetime. This number of complexes, N, will be determined by the cycling time (between quinol and quinone) of the quinol, by diffusion constants, by association/dissociation rate constants, and by the distances between components. (N.B., In the following, N represents the number of acceptors within range of a quinol of lifetime t. The actual number of acceptors which lie in the area swept out by a single given quinol will be rather lower than N.)
  • The other extreme type of molecular organisation might be loosely termed 'solid state' [19,20]. The bc complexes themselves can be considered to be such solid-state devices, since electrons which enter a complex from quinol are not transferred to other acceptors in like complexes. One could similarly envisage that electron transfer from, for example, a dehydrogenase to a bc1 complex could occur by such a solid-state mechanism (Fig. 1B), with the required quinone being permanently associated with each dehydrogenase/bc unit. Indications that such complexes exist come from observations that such structures as site I/bc units [35-37], succinate dehydrogenase/bc units [38,39] and bf/Photosystem I units [40] may be isolated. Furthermore, the vesicle reconstitution experiments of Ragan et al. [41-43] demonstrated that stoichiometric associations between Complex I and Complex III could occur if sufficiently high protein concentrations were used. In such a case, no 'Q-pool' behaviour was observed. Only when sufficient lipid was added was Q pool behaviour restored [42]. It was suggested, however, that the mobility in this case was provided by movement of protein-quinone complexes, rather than by free quinone. The notion of permanently bound quinone was presented in extreme form recently by Yu and Yu [44], who claim to have ruled out the possibility that exchange between free and bound forms of ubiquinone occurs. In such 'solid-state' reactions, reaction rate becomes limited by an internal rate constant of one of the component units. Rates of useful collisions do not determine flux and the appropriate electron transferring complex is present at all times.
  • The two cases described above are clearly extreme examples and intermediate modes of operation are feasible. The essential figure of interest is N, the number of units which can potentially interact within the turnover time of the system, varying from 1 (solid state behaviour) to all ('solution' behaviour). In practice, it will generally become impossible to distinguish a system with an N in excess of 10 from ideal solution behaviour.
  • A further complication is the possibility that patches of like components may form in certain regions of the membrane. .. In such a situation of patching, it becomes feasible to favour particular electron transfer pathways between components which patch together, even although on a local scale the liquid state is still operative. A switch between random and non-random component distribution in membranes as a means of control has been suggested by Schiffman [47].
  • In practice, it would actually be difficult to distinguish such saturation of binding sites from an effect caused by loss of ideal solution behaviour, at the high concentrations of quinone which would be required.
  • The first suggestion that the ubiquinone acts as a lipid soluble cofactor between dehydrogenases and bc1 complexes in mitochondria was made by Green in 1962 [21].
  • The idea that mobility of some sort must exist is evident from the stoichiometry of the components and their kinetic behaviour. For example, in mitochondria, cytochrome bc1 complex is generally present in a significant molar excess over site I and yet NADH is able to reduce all of the cytochrome bc1 complexes rapidly. Similarly, succinate dehydrogenase (generally around one-third per bc1 complex) is able to reduce all of these same cytochrome bcl complexes. .. Further evidence for the mobility comes from an extension of the Kröger and Klingenberg approach to include loosely-bound inhibitors [53], from studies of the additivity of rates of simultaneous oxidation of several substrates (Ref. 54, and the more detailed analysis of Ref. 3), and from the experiments of Schneider et al. [55,56] which showed that diffusion distance between components could be changed by lipid dilution.
  • Such studies demonstrate that the simple notion of a mobile quinone pool in stoichiometric excess of the electron-transferring multiproteins is in essence, at least, operative in systems which are undergoing multiple-turnover electron transfers.
  • Although the notion of the mobile quinone pool is borne out experimentally from many points of view, there is a number of observations which clearly indicate that caution must be exercised in its general application. Additional factors (such as discussed in subsection IIA) which prevent the ideal behaviour must then be considered. For example, Gutman [3] has discussed anomalies in the additivities of rates of substrate oxidation in mammalian mitochondria which are not always in accordance with the predictions of a fully mobile quinone pool, and has suggested that the quinone pool becomes functionally compartmented into domains.
  • the redox chemistry is complicated by the fact that the overall two-hydrogen-atom redox change of Q/QH2 must be considered in terms of individual one-electron and one-proton transfers, and hence allows many possible routes of redox equilibration.
  • the two stoichiometric inhibitors of the bc1 systems, antimycin A [50] and myxothiazol [151,152] are without effect on quinol-plastocyanin oxidoreductase activity of the bf complexes.
  • Electron and proton transfers through quinones: There is no evidence to suggest that either hydrogen atom (1H+ plus le-) or hydride ion (1H+ plus 2e-) transfers are able to occur.
  • in aprotic media, where the species Q, Q- and Q2- are feasible, one generally obtains two reversible waves in cyclic voltammetric studies, .. In more protic solvents, however, the behaviour becomes much more complex, as protonated species begin to dominate the reaction pathways. The waves often become irreversible when chemical (in this case protonation/deprotonation) reactions have to occur to allow the electrochemical transfers, and reductive and oxidative waves can become very widely separated.
  • .. at around pH 7 in aqueous media, the active reductant quinol species is the anionic quinol, QH-, whereas the active oxidant quinone species is the protonated quinone, QH+.
  • .. a number of cytochrome bc1 preparations have been described which contain substoichiometric amounts of ubiquinone-10, and yet are able to function catalytically when supplied with a range of quinol donors (e.g., Refs. 8 and 117 119). .. It appears unlikely, therefore, that the copurified quinone of the bc complexes plays an essential role as a permanently associated prosthetic group, but instead is essentially 'trapped' at its site of interaction during purification.

Some numerical values

  • 2·106 cm2/g protein for the surface area of the inner membrane [25]
  • cytochrome bc1 content of around 0.2 nmol per mg protein [26]
  • area per bc1 dimer of around 200 000 Anström2 (2000 nm2) [27]
  • diffusion coefficient, D, for ubiquinone of 10-8 cm2·s-1 by analogy with phospholipid; D of 1·10-9 cm2·s-1 has recently been suggested [14]
  • throughput of the cytochrome bc1 complex can be as high as 200 electrons/s per monomer in state 3 mitochondria (Einstein-Smoluchowski equation)
  • ratio of active quinone/bc1 monomer of at least 5 [22]
  • turnover time per Q species of around 50 ms (assuming two electrons are throughput to cytochrome c from each QH2 ↔ Q cycle)
  • distance travelled x for the quinol form (assuming that it is quinol for only one-half of the 50 ms cycle) of around 2240 Angström (224 nm)
  • approx. 80 cytochrome bc1 dimers are potentially reachable by a given quinol during its lifetime in state 3
  • assuming a bc1 throughput of around 20 electrons s-1 per monomer
  • then x becomes 7000 Angström (700 nm)
  • N rises to around 800
  • the entire length of UQ-10 is 56 Angström [179]

Comments

  • The concept of supercomplexes has received increasing attention, with limited connection between the original literature (see references in Rich 1984) and more recent reviews, reflected partially in different terms used for identical concepts. Here a harmonization of fundamental terms is attempted:
Rich (1984) Enriquez, Lenaz (2014)
stoichiometric associations between Complex I and Complex III - in such a case, no 'Q-pool' behaviour was observed super-assembly in the physiological role of coenzyme Q
solid state model solid model
liquid state model random collision model
"Solid state" and "liquid state" as extremes of molecular organisation .. The essential figure of interest is N - the number of acceptors within range of a quinol of lifetime t Recently, the plasticity model has been developed to incorporate the solid and the random collision model as extreme situations of a dynamic organization


Cited by

  • Komlodi et al (2021) Simultaneous measurement of respiration and redox state of the Coenzyme Q pool in mitochondrial preparations. Bioenerg Commun 2021.3 doi:10.26124/bec:2021-0003


Labels:



Enzyme: Complex III  Regulation: Q-junction effect 



MitoFit 2021 CoQ