The inhibition of tissue respiration and alcoholic fermentation at different catabolic levels by ethyl carbamate (urethan) and arsenite

Abstract

1. A hypothesis is given concerning the action of urethan and arsenite on malignant growth. Two assumptionsares made:-

(a) the enzyme system responsible for energy production in malignant tumours is working at maximal rate, contrary to the corresponding enzyme system in normal tissues. (b) a given concentration of urethan or arsenite blocks an equal part of the sensitive enzyme(s), by which a measurable effect of a small concentration of these inhibitors on the catabolism will only be obtained in case of maximal turnover rate.

2. Experiments with kidney and liver minces and with yeast have shown that indeed the inhibition caused by urethan and arsenite increases with increasing rate of respiration or fermentation.

3. If the enzyme concentration is not considered to be negligible as compared to the substrate concentration, as is done in the theory of and , the increase of inhibition with increasing turnover number can be made plausible by enzyme kinetics for the much simplified case of one single enzyme.

4. The dependence of inhibition upon the turnover number of the catabolic enzyme system in tumours is discussed in relation to other possible causes of the effect of urethan and arsenite on malignant growth.