Respiration coupling with phosphorylation

In true fermentation, the free energy drop between substrate (say glucose) and anaerobic end products is always modest by comparison with respiration, because fermentation is never based on electron transfer chains coupled to phosphorylation. Rather, true fermentations depend upon a variety of oxidation-reduction reactions involving organic compounds, C02, molecular hydrogen, or sulfur compounds. All these reactions are inefficient in terms of energy yield (moles ATP per mole substrate fermented), and, therefore, the mass of cells obtainable per mole of substrate is much smaller than with respiratory-dependent species. 

Like most bacteria, the Microtox strain has many metabolic pathways which function in respiration, oxidative phosphorylation, osmotic stabilization, and transport of chemicals and nutrients into and out of the cell, and which are located within or near the cytoplasmic membrane. The luciferase pathway [9], which functions as a shunt for electrons directly to oxygen at the level of reduced flavin mono-nucleotide, is also located within the cell membrane complex. This, coupled with lack of membrane-aided compartmentalization of internal functions, gives many target sites at or near the cytoplasmic membrane. These factors all contribute to a rapid response of the organisms to a broad spectrum of toxic substances. 

In Chapter 20, we saw that a proton gradient across the inner mitochondrial membrane drives the phosphorylation of ADP in respiration. The mechanism of photophosphorylation is essentially the same as that of the production of ATP in the respiratory electron transport chain. In fact, some of the strongest evidence for the chemiosmotic coupling of phosphorylation to electron transport has been obtained from experiments on chloroplasts rather than mitochondria. Chloroplasts can synthesize ATP from ADP and P in the dark if they are provided with a pH gradient. 

A third group of compounds include the antibiotics oligomycin and auro-vertin which inhibit phosphorylation. Due to the mandatory coupling between respiration and phosphorylation, they block also the respiration when it is coupled to phosphorylation, but not when it is uncoupled. Very likely, they combine irreversibly with some intermediate in the coupling sequence. The removal of the oligomycin (or aurovertin) block in phosphorylating mitochondria by uncouplers would indicate that uncouplers react at a site located between the respiratory chain... 

In environments lacking a suitable external electron acceptor - such as dioxygen, sulfate, or ferric iron - respiration is not possible. Here, many organic compounds may be metabolized by fermenting microorganisms. Microbes of this class may create ATP by a direct coupling mechanism, using a process known as substrate level phosphorylation, SLP with an ion translocation mechanism like that employed by respirers, as already described or by a combination of SLP and ion translocation.1... 

Stucki (1980, 1984) applied the linear nonequilibrium thermodynamics theory to oxidative phosphorylation within the practical range of phosphate potentials. The nonvanishing cross-phenomenological coefficients Ly(i v /) reflect the coupling effect. This approach enables one to assess the oxidative phosphorylation with H+pumps as a process driven by respiration by assuming the steady-state transport of ions. A set of representative linear phenomenological relations are given by... 

SQR (respiratory complex II) is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain (Saraste, 1999). QFR participates in anaerobic respiration with fumarate as the terminal electron acceptor (Kroger, 1978 Kroger etal., 2002) and is part of the electron transport chain catalyzing the oxidation ofvarious donor substrates (e.g., H2 or formate) by fumarate. These reactions are coupled via an electrochemical proton potential (Ap) to ADP phosphorylation with inorganic phosphate by ATP synthase (Mitchell, 1979). 

ATP synthase equilibrate with the aqueous phases of the matrix and cytosol (or incubation medium). While this may seem intuitive, in view of the extremely high conductance of water to protons, there have in recent years been a number of reports of significant anomalies in the thermodynamic and kinetic relationships between respiration, ATP synthesis and the measured AjUH+ sufficient to lead some investigators to suggest that this last parameter does not represent the true intermediate in the coupling of respiration to phosphorylation [24],... 

There is some indications that mitochondria possess a mechanism of self-elimination. This function was ascribed to the so-called permeability transition pore (PTP). The PTP is a rather large nonspecific channel located in the inner mitochondrial membrane. The PTP is permeable for compounds of molecular mass <1.5 kDa. The PTP is usually closed. A current point of view is that PTP opening results from some modification and conformation change of the ATP/ADP antiporter. Oxidation of Cys56 in the antiporter seems to convert it to the PTP in a way that is catalyzed by another mitochondrial protein, cyclophilin. When opened, the PTP makes impossible the performance of the main mitochondrial function, i.e., coupling of respiration with ATP synthesis. This is due to the collapse of the membrane potential and pH gradient across the inner mitochondrial membrane that mediate respiratory phosphorylation. Membrane potential is also a driving force for import of... 

An interesting hypermetabolic myopathy was discovered and biochemically explored by Luft et al. (L7). There was no evidence of hyperthyroidism, and mitochondria from biopsied muscle had a high rate of respiration and a loosely coupled state of oxidative phosphorylation. A few other cases of unusual myopathies with loosely coupled mitochondria have since been described (e.g., S12), although it does not seem that this is a single disease entity. 

---