The receptor as a coenzyme or other small molecule

The question was then posed does oxine act on bacteria by removing metals essential to bacterial welfare, or does it cause traces of metal ions to become more toxic to the bacteria The latter proved to be the case. When we incubated Staphylococcus aureus in distilled water, with oxine, with iron, and then with both chemicals together, subsequent plating out on nutritive medium showed that only bacteria that had been exposed to both oxine and iron were killed (see Table 2.3) (Albert, Gibson and Rubbo, 1953). In further work, it was found that iron is a necessary co-toxicant for all kinds of bacteria, whereas copper takes over this function for fungi. 

Oxine (HM) Ferrous sulphate (UM) Growth (Staphylococcus aureus) 

Before long, several substances with chemical constitutions very different from that of oxine, and using quite different atoms to form the chelate ring, were found to have the typical oxine mode of action on bacteria. This typical action is definable as the rapid killing of bacteria and fungi at high dilutions, requiring 

Cobalt is well known for its ability to break an oxidatively destructive chain reaction catalysed by another metal (cf. Baur and Preis, 1936). This suggested to the Dutch workers that the iron and copper complexes of oxine, pyrithione, and dimethyldithiocarbamic acid were oxidatively destroying thioctic acid (dihydrolipoic acid) (2.28) which is the essential coenzyme for the oxidative decarboxylation of pyruvic acid. This was confirmed when they found pyruvic acid accumulating in the medium (Sijpesteijn and Janssen, 1959 also personal communications from these authors). The receptor in all three examples is the small molecule (2.28) although, at the time, it caused surprise to find one of such low molecular weight. 

An earlier example of a coenzyme acting as a receptor is the porphyrin molecule of cytochrome oxidase. The lethal action of hydrogen cyanide, counter-selective for mammals, follows directly from the binding of this poison to the free valence of the chelated iron in the porphyrin. Many bacteria, lacking this enzyme, are not affected. 

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