A Non-Particulate,Dinitrocresol-Resistant,Glycolytic,Phosphorylating Mechanism Present in Malignant and Certain Normal Tissues

Abstract

Summary

1. In liver and brain there are two distinct mechanisms for phosphorylation, which may be separated by centrifligation of the tissue homogenates: (1) particulate elements dependent on oxidation of succinate or other substrates of the tricarboxylic acid cycle and (2) water-soluble or at least water-borne systems glycolyzing hexose diphosphate. In the Walker 256 tumor the major part of the phosphorylating effect appears to be induced by the water-soluble, hexose diphosphate glycolyzing system, which functions equally well under aerobic and anaerobic conditions. 2. While the oxidative phosphorylation carried out by liver and brain particles with succinate or a-ketoglutarate is readily blocked by extremely dilute solutions of dini-troeresol, the water-borne, glycolytic, phosphorylating system which' passes into the supernate on centrifuging the homogenate is not suppressed by dinitrocresol, even when used at concentrations from 100- to 500-fold those which completely suppress aerobic phosphorylation of washed liver particles. The phosphorus uptake of the tumor particles, which in any case is substantially less than that of liver and brain particles, is only partially suppressed under anaerobic conditions. Furthermore, a substantial part of the activity appears to be maintained at concentrations of DNC which completely block phosphorus uptake by liver particles. The phosphorus uptake of the tumor supernate is, like that of the liver and brain supernates, entirely unaffected by concentrations of DNC 100- to 500-fold those required to suppress the oxidative phosphorylation of liver particles. 3. The peculiar behavior of tumor particles under aerobic conditions and also when exposed to certain concentrations of DNC suggests the possibility that at least a part of the phosphorus uptake of tumor particles may be attributable to the anaerobic phosphorylating mechanism, which, even after extensive washing, remains attached to or associated with the tumor particles.