Studies on the Action of Antibiotics on Bacterial Metabolism. V On A Site of the Action of Chloramphenicol

Abstract

At present, considerable informations were presented on the inhibitory actions of chloramphenicol on enzymatic reactions in both growing and resting bacterial cells. The following reactions are reported as to the inhibitions of chloramphenicol; the formation of adaptive enzyme^1,2) or the synthesis of protein,^3–5) the activity of bacterial lipase,⁶⁾ the reduction of nitrite,⁷⁾ the metabolism of aromatic amino acids^8–10) and the oxidation of dicarboxylic acids.^11–12)

Recently the production of α-ketoglutarate with many kinds of microorganisms has been reported and also a number of studies^{17),20),35–39)} put forward on the mechanism of α-ketoglutarate fermentation.

Some pathways of the production of α-ketoglutarate from glucose were already suggested as follows; (I) α-ketoglutarate was produced from glucose via pyruvate and (II) α-ketoglutarate was formed directly from glucose (C₆ → C₅+ CO₂), so that its formation did never occur through pyruvate nor by condensation of pyruvate with the fragment such as C₂- or C₃-compound produced during fermentation. The first pathway (I) may again be divided into following two ways; (a) the one via the tricarboxylic acid cycle and (b) the other via a pathway different from the tricarboxylic acid cycle. Katagiri and Tochikura⁴⁰⁾ supported the pathway (I)-(b) with coli-aerogenes bacteria and suggested a new pathway in which α-ketoglutarate is formed by the condensation reaction of pyruvate and acetyl-Co A.

As regards the action of chloramphenicol upon the reaction system of the formation of α-ketoglutarate from pyruvate, there suggested at least three ways; the first was the inhibiting action on the formation or breakdown of citrate (in case of (I)-(a)), the second was its action on the condensation reaction of pyruvate and acetate, (in case of (I)-(b)) and the third was the case in which E. coli fermented pyruvate specifically in the presence of chloramphenicol by other pathways different from both conventional tricarboxylic acid cycle and pyruvate-acetate reaction.

In the present papers, investigations have been undertaken to trace the mode of action of chloramphenicol with the purpose of examining of the possibilities of these three ways mentioned above.