Effect of 2-Deoxyglucose on Cell Wall Formation in Saccharomyces cerevisiae and Its Relation to Cell Growth Inhibition

Abstract

The growth inhibition and the lysis of Saccharomyces cerevisiae caused by 2deoxy-D-glucose (2-DG) were shown to be a consequence of unbalanced cellular growth and division. The lysis, but not the repression of growth and osmotic fragility of cells, could be suppressed by the addition of mannitol as an osmotic stabilizer. This result, as well as the morphological changes observed in the cells and changes in the chemical composition of the cell walls, showed that S. cerevisiae grown in the presence of 2-DG formed weakened cell walls responsible for the osmotic fragility. Evidence is presented for the first time demonstrating the incorporation of 2-DG into yeast cell wall material. Other data suggest that the inhibition of yeast growth by 2-DG results from an interference of phosphorylated metabolites of 2-DG with metabolic processes of glucose and mannose involved in the synthesis of structural cell wall polysaccharides.

Dynamics of cell wall structure in Saccharomyces cerevisiae

“…Increased sensitivity to sonication [150,156] and hypotonic shock [157,158] has also been used to detect mutants with a cell wall defect. 2-Deoxyglucose, which is incorporated in the cell wall and causes cell lysis in growing areas, may presumably also be e¡ectively used to identify cell wall mutants [159,160]. Alternatively, the culture ¢ltrate may be screened for increased amounts of cell wall proteins or for incomplete CWP^polysaccharide complexes indicative of defective cell wall assembly [84,150].…”

A family of hexosephosphate mutases in Saccharomyces cerevisiae

“…The complexity of the effects of 2-deoxyglucose and the pro-posed biochemical mechanism for its toxicity have been summarized by Gancedo and Serrano (1989). Osmotic lysis due to a weakened cell wall caused by the inhibition of mannan and glucan synthesis accounts for the lethal effect (Biely et al, 1971;Johnson, 1968). One of the participating reactions in the conversion of 2-deoxyglucose into its inhibitory form, UDP-2-deoxyglucose, is catalysed by PGM.…”

A comparison of the toxic effects of 2‐deoxy‐D‐glucose and 2‐deoxy‐2‐fluoro‐D‐hexoses on Saccharomyces cerevisiae cells and protoplasts

“…Growth was followed by measuring t h e absorbance at 420 nm of t,he cell suspensions in 0.2 cm wide cuvettes. Preparation and cultivation of protoplasts : Protoplasts were prepared from exponential phase cells grown in t h e RIDDER medium by the procedure given elsewhere (BIELY et al 1973). After tn-o washings with 0.8 M mannitol solution in 0.1 M phosphate buffer (pH 6), the protoplasts were suspended in the synthetic medium containing 2% glucose or mannose supplied with 0.7 M manni-to1 and grown a t 30 "C under occasional stirring.…”

“…1975, TSIOMEEKO et al 1978. The inhibition of polysaccharide synthesis results in lysis of growing cells due t o disturbance of balanced cell wall growth (JOHNSON 1968, BIELY et al 1973.…”

“…1971, KRLTKY et al 1975) and FG (BIELY et al 1973) on growth and sonie metabolic activities of 8. cerevisiae cells and protoplasts showed that FG is more toxic than DG. Particularly t.he synthesis of cell wall glucan was found to be extremely FG-sensitive (BIELY et al 1973). Siniilar studies with FM have not been done yet,.…”