Effect of inhibitors on the metabolism of cells in tissue culture and on foot-and-mouth disease virus synthesis

Abstract

Metabolic studies have been made with suspensions of pig-kidney cells grown in tissue culture. Oxygen uptake, carbon dioxide output and glycolysis have been measured in the presence of arsenite, fluoride, cyanide, 2,4-dinitrophenol, and upon the addition of glucose, succinate and glutamate. The cells possessed the conventional glycolytic, the Krebs cycle and terminal oxidative pathways of metabolism, together with some aspects of respiratory control as demonstrated by the Pasteur and Crabtree effects. Cells between 2 and 9 days in tissue culture showed a progressive decline in oxygen uptake and an increase in glycolytic activity. It was found that the energy for a single multiplication cycle of foot-and-mouth disease virus could be supplied by the oxidation of glucose or of endogenous fat. This could be completely replaced by glycolysis in the presence of inhibitors of terminal oxidations. Arsenite and fluoride inhibition of virus multiplication was not primarily due to their action on the Krebs cycle and glycolysis respectively. Virus synthesis was inhibited by p-fluorophenylalanine but not by ethionine, 2,6-diaminopurine, azaguanine, thiouracil and azathymine.