Metabolic studies with 2-deoxyhexoses: I. Mechanisms of inhibition of growth and fermentation in baker's yeast

I. A study has been made to elucidate the mechanisms involved in the inhibition produced by 2-deoxyhexoses (2-deoxyglucose and 2-deoxygalactose) on yeast growth and fermentation.2. Inhibition of both growth and fermentation were dependent on the phosphorylation of the 2 deoxysugar. They cannot be explained either by an interference of the 2-deoxysugar with the transport and phosphorylation of the substrate or by a block of glucose phosphate isomerase (D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9) by 2-deoxyglueose-6-phosphate.3. A major factor in the inhibition of glycolysis seems to be an interference with the entrance of the fermentable sugars into the cells by the intracellular accumulated 2-deoxyhexoses phosphates. Inhibition of growth was much higher than of glycolysis, and it is not a direct consequence of the latter. It seems to be related to a block in the synthesis of structural polysacchafides by a trapping of uridine nucleotides by the phosphorylated derivatives of the 2-deoxysugars.4. Besides its inhibitory effect on glycolysis, the 2-deoxyglucose had a lethal effect on yeast which seems to be dependent on the presence of a source of energy and was more apparent in growing than in resting cells.This work was supported in part by a Grant (RG-8o4 I) from the United States Public Health Service.Peer reviewe