Phosphorylation of 2-deoxy-D-glucose by yeast hexokinase: Competition between 2-deoxy-d-glucose and glucose

Multifaceted effects of antimetabolite and anticancer drug, 2‐deoxyglucose on eukaryotic cancer models budding and fission yeast

“…This mutant was shown to be resistant to 2‐DG when grown on carbon sources such as raffinose which is not a substrate for hexokinase . This observation is consistent with the previous report that the toxic product of 2‐DG is 2‐DG‐6‐P which will be formed only after the action of hexokinase on 2‐DG .…”

“…The entry of 2‐DG into the cells is mediated by hexose transporters, and these transporters represent integral membrane proteins encoded by at least 17 genes ( HXT1 – 17 ) in S. cerevisiae and by 8 genes ( ght1–8 ) in S. pombe . In yeasts, the formation of 2‐DG‐6‐P by hexokinase was reported as early as 1955 . Upon entry into the cells, the cytoplasmic hexokinase acts on 2‐DG to form 2‐DG‐6‐P.…”

“…In S. cerevisiae, a mutant resistant to the toxic effects of 2‐DG was isolated, and this resistance was assumed to be due to the presence of an intracellular phosphatase able to hydrolyze the toxic 2‐DG‐6‐P . The enzyme has its maximum activity in the physiological range and its presence reduced the accumulation of 2‐DG‐6‐P indicating the presence of a gene detoxifying the toxic 2‐DG product; 2‐DG‐6‐P .…”

Oxidative phosphorylation by subcellular particles from yeast

“…Since it had been found in experiments not shown here that particles prepared by washing with sucrose contained appreciable quantities of glucose 6-phosphate dehydrogenase, parallel experiments were included here in which 2-deoxyglucose was substituted for glucose in the ATP-trapping system. Woodward & Hudson (1955) have shown that yeast hexokinase phosphorylates 2-deoxy.. glucose and glucose at comparable rates. However, the further metabolism of the phosphorylated product should be much slower with 2-deoxy sugar, and thus the latter is the preferred acceptor in many situations.…”

Effects of d-glucosamine and glucose analogues on glycogen biosynthesis in vitro

“…The observation that glucose phosphorylation in brain is inhibited competitively by D-glucosamine and N-acetyl-D-glucosamine (Harpur & Quastel, 1949) was followed by extensive work on the effects of these amines and their analogues, e.g. 2-deoxy-D-glucose, on glucose transport across cell membranes (Nakada, Morita & Wick, 1955;Woodward & Hudson, 1955), glycolysis (Harpur & Quastel, 1949;Woodward, 1952;Woodward, Cramer & Hudson, 1953;Woodward & Hudson, 1953Tower, 1958), respiration (Woodward & Hudson, 1954;Tower, 1958) and tissue growth (Ely, Tull & Hard, 1952;Woodward, 1952;Ely, Tull & Schanen, 1953;Quastel & Cantero, 1953;Woodward & Hudson, 1953;Ball, Wick & Sanders, 1957;Bernstein & Black, 1959). Srinivasan & Quastel (1958), however, observed that D-glucosamine or N-acetyl-D-glucosamine stimulates the formation of oligosaccharides containing the respective amino sugar by yeast invertase, yeast lactase and extracts of Aerobacter aerogenes.…”