Respiration, and phosphorylation

Respiration and phosphorylation usually are tightly coupled processes if phosphorylation stops, so, as a rule, does respiration and vice versa. As an example, respiration slows down greatly if mitochondria run out of ADP (fig. 

Let us now determine what the material particle, possessing the chemical energy excess, provides for the communication channel (conjugation) between respiration and phosphorylation. According to data obtained by biochemists, there are three highly active intermediate products... 

Chemical reaction conjugation on membrane catalysts is considered [30,31] as the simplest model of conjugated processes proceeding in mitochondria. Some functions of this model may be applied to the description of several aspects of respiration and phosphorylation conjugation mechanism. 

Therefore, as a mitochondrion membrane is broken, it somewhat disrupts communications between two conjugated reactions (respiration and phosphorylation). Hence, as expected, phosphorylation is completely terminated. This kinetic behavior of the system, both unclear and unusual at first glance, is quite logical, and is associated with the membrane origin of the ATP synthesis. 

The above discussion, which mostly considers kinetic and chemical aspects to explain respiration and phosphorylation unconjugation, makes clear the action of uncouplers of different origins. Moreover, no principal difference in the mechanism of uncouplers and open mitochondrial surface is observed, because uncouplers increase membrane conductivity for H+ ions and, therefore, promote its partial break in places of uncoupler injection. 

Unfortunately, although the scheme shown in Figure 3.4 clearly presents the type of chemical conjugation between respiration and phosphorylation, nevertheless, biochemists experience difficulties with the perception of a purely chemically formulated scheme. We suggest that this very circumstance prevents them from an adequate perception of the whole scheme. All in all, this is not surprising because for biochemists scheme visualization is associated with an indication of directions or rather process routes, frequently without taking into account stoichiometry and other physical processes that are absolutely necessary for chemists. 

At the molecular level, the scheme of the H+-ATP-synthase reaction mechanism is quite simple. It illustrates the interaction between two conjugated reactions respiration and phosphorylation, and the exclusive role of the H+ ions in the structural organization of this interrelation. Moreover, energy (i.e. thermodynamic) conjugation is reasonably substantiated from a physicochemical position. 

Kohler, P. and Bachmann, R. (1980) Mechanisms of respiration and phosphorylation in Ascaris muscle mitochondria. Mol. Biochem. Parasitol. 1 75-92. 

Kaiser, et al. [276] studied another example of inhibition of phosphorylation process by coumarins. In that study, it was shown that imperatorin, a fiiranocoumarin from Imperatoria ostruthium L. and Ammi majus L., inhibited respiration and phosphorylation of isolated mitochondria of the liver in the presence of succinate [276,326]. 

In a number of cases, the eflBciency of oxidative phosphorylation in the mitochondria of developing systems, as judged by the magnitude of the P 0 ratio, has been found to be less than that of mitochondria from fully differentiated tissues, and it has been suggested that such mitochondria may not yet have developed all of the fundamental machinery necessary for coupling respiration and phosphorylation [blowfly muscle (Lewis and Slater, 1954), rat muscle (Kiessling, 1962), honeybee flight muscle (Balboni, 1967), rat liver (Mintz et al., 1967), and rat brain (Milstein et al, 1968)]. 

Vasington FD, Murphy JV (1962) Ca " uptake by rat kidney mitochondria and its dependence on respiration and phosphorylation. J Biol Chem 237 2670-2677... 

A summary of the major findings on the incorporation of labeled amino acids into proteins is (1) every tissue that has been tested has been found to incorporate into its proteins, in vitro as well as in vivo, every common labeled amino acid (n-form) presented to it (2) so far one amino acid which is not a normal protein constituent—ethionine—has been found to be incorporated, two others—a-aminoadipic acid and a-aminobutyric acid —were not incorporated (3) the rate of incorporation varies with the amino acid and the tissue from approximately 0.1 to 10 micromoles per gram of protein per hour (4) the incorporation of a single amino acid appears to be largely independent of the presence of others except for specific accelerating effects of a few amino acids (5) labeled amino acids are incorporated by peptide linkage (6) in most but not all cases inhibitors of respiration and phosphorylation inhibit amino acid incorporation and protein synthesis (7) there is evidence that in some cases cofactors (unidentified) are involved. 

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... 

A partial uncoupling of respiration and phosphorylation would render part of the respiration ineffective and would thus result in a higher basal rate. 

---