Carriers, respiratory

FIGURE 19-33 Bacterial respiratory chain, (a) Shown here are the respiratory carriers of the inner membrane of E. coli. Eubacteria contain a minimal form of Complex I, containing all the prosthetic groups normally associated with the mitochondrial complex but only 14 polypeptides. This plasma membrane complex transfers electrons from NADH to ubiquinone or to (b) menaquinone, the bacterial equivalent of ubiquinone, while pumping protons outward and creating an electrochemical potential that drives ATP synthesis. 

Oligomycin is an antibiotic that inhibits respiration in intact mitochondria. Respiration is not inhibited in uncoupled mitochondria, i.e., those mitochondria in which 02 consumption occurs but in which no ATP is synthesized. Thus, oligomycin does not block respiratory carriers, in contrast to inhibitors such as rotenone and cyanide. Instead, oligomycin blocks proton translocation through the F component to the F( component, through a specific interaction with a subunit of the membrane-associated F . The subscript o in the term F was originally used to indicate the oligomycin-sensitive" complex. 

Many of these copper proteins are enzymes, and the copper is a part of their active group (Nos. 1, 10-14 in Table 4), while others have no known enzyme activity (Nos. 2-9). As far as is known, none of these proteins functions as a respiratory carrier, as hemocyanin does in mollusks. It has been suggested, but not proven, that the human liver copper protein of Morell et al. (M32) and the hepatic mitochondrocuprein of Porter et al. (P13, P15) may function as copper storage proteins, similar perhaps to ferritin in the case of iron. 

An effective respiratory carrier must be able to pick up oxygen from the lungs and deliver it to peripheral tissues. Oxygen dissociation curves for substances A and B are shown in Figure 10.4. What would be the disadvantage of each of these substances as a respiratory carrier Where would the curve for an effective carrier appear in the figure ... 

A substance must exhibit the following characteristics before it can be considered to behave as a respiratory carrier (Potter, 1940) ... 

Whether coenzyme I was concerned in the earlier experiments was not determined and has not mnce been determined. The evidence from these studies was suggestive of the participation of ascorbic acid as a respiratory carrier. It was, however, only suggestive and not conclusive, for the authors did not demonstrate either with their lactate dehydrogenase or hexose diphosphate systems the direct reduction of dehydroascorbic acid to ascorbic acid. 

Evidence for the Action of Ascorbic Acid-Dehydroascorbic Acid as a Respiratory Carrier in vivo... 

If the DHA-AA system is acting as a respiratory carrier in vivo, then one would expect that the subjection of plant tissues to anaerobic conditions would lead to a fall in concentration, if not to the complete disappearance of DHA. An analogous phenomenon is certainly observed with cytochrome in portions of intact potato tissue. The reduction of cytochrome under anaerobic conditions and its reoxidation on admittance of air may be observed spectroscopically by visual examination of the cytochrome spectrum of the tubers in vivo (Hill and Scarisbrick, 1951). Moreover, these changes are produced quite rapidly within 60 to 90 minutes of the alteration of the atmosphere around the tubers (HiU and Barker, 1951). 

Although the biochemical evidence would suggest therefore that ascorbic acid may act as a respiratory carrier, the previous remarks have served to emphasize that, as yet, we have no clear evidence that it is so... 

The botanical biochemists have unusual opportunities for studying simple biological systems in which ascorbic acid may participate. The present writer was interested to learn from another paper in this volume (Mapson, 1953) that there is no clear evidence from plants that ascorbic acid acts as a respiratory carrier in vivo. On the other hand, the reduced form (AA) can certainly act as a hydrogen donor. 

Figures 8 and 9 show the sequential arrangement of the respiratory carriers. These carriers have prosthetic groups that can be reversibly oxklized and reduced by gaining or loosing electrons and have redox potential increasing from — 0 35 to -I- 0-81 V. The net drop of about 1 1 V corresponds to a total drop in free energy of about 52,000 cals. (Fig. 9). The arrangement of the respiratory carriers permits a stepwise liberation of this energy, which can then easily be trapped and conserved.

Fio. 10. Schematic representation of the organization of the respiratory carriers in the four complexes, described by Green and associates. 

Fio. 11. Difference spectra of the respiratory carriers of rat-liver mitochondria. The solid line illustrates the optical density under aerobic conditions, and the dashed line... 

Fig. 13. Schematic illustration of the asymmetric orientation of the respiratory carriers in the mitochondrial coupling membrane. This specific orientation ( loops ) drives the separation of charges across the mitochondrial membrane, and thus creates...

Flavoprotein, Warburg s yellow enzyme, is a widely distributed natural pigment which acts as a respiratory carrier in the oxidation of hexose phosphates, malate and alcohol. It is a conjugated protein, the prosthetic flavin of which was discovered by Szent-Gybrgyi, who named it cytoflave prior to its indentifica-tion with vitamin Bg. In the absence of the protein component, the flavin has no respiratory activity. 

Functions.— Riboflavin phosphate, when combined with a protein, forms the respiratory carrier, or yellow catalyst of Warburg, which takes part in the dehydrogenation of glucose, lactic acid and other important intermediate metabolites. Hence, riboflavin is probably required for the growth and maintenance of every animal tissue. 

Glucose, lactate, succinate, aliphatic and amino acids, and other substances oxidised by animal tissues are very stable in solution, and are not obviously affected by atmospheric oxygen at ordinary temperatures. In the tissues, however, they are rapidly and effectively oxidised at body temperature, which for cold-blooded animals may be as low as 10 C. These combustions are brought about by a series of chain reactions, often of surprising complexity, which include (i.) respiratory catalysts, and (ii.) respiratory carriers. 

A. Dehydrogenases, dehydrases, oxido-reductases or hydrogen-transportases are widely distributed in vertebrate, invertebrate and plant tissues. Most of them are highly specific enzymes, and operate in association with respiratory carriers, which are much less specific. As a class, they are inhibited by narcotics, but not by cyanide. Important examples are ... 

In the yellow enzyme, the prosthetic group is the phosphate of ribofiavin, or vitamin Bg (p. 256). The flavoprotein carrier differs from hematin carriers in three respects (i.) it does not contain iron and is not inhibited by CO, HCN and H S (ii.) it requires the presence of an additional carrier, co-enzyme II (iii.) it is capable of being reoxidised by free oxygen without the aid of an oxidase. At the same time, flavoprotein can work in conjunction with cytochrome to form a system containing three successive respiratory carriers. 

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