H₂O₂, but not menadione, provokes a decrease in the ATP and an increase in the inosine levels in Saccharomyces cerevisiae

Abstract

When Saccharomyces cerevisiae cells, grown in galactose, glucose or mannose, were treated with 1.5 mM hydrogen peroxide (H 2 O 2 ) for 30 min, an important decrease in the ATP, and a less extensive decrease in the GTP, CTP, UTP and ADP-ribose levels was estimated. Concomitantly a net increase in the inosine levels was observed. Treatment with 83 mM menadione promoted the appearance of a compound similar to adenosine but no appreciable changes in the nucleotide content of yeast cells, grown either in glucose or galactose.Changes in the specific activities of the enzymes involved in the pathway from ATP to inosine, in yeast extracts from (un)treated cells, could not explain the effect of H 2 O 2 on the levels of ATP and inosine. Application of a mathematical model of differential equations previously developed in this laboratory pointed to a potential inhibition of glycolysis as the main reason for that effect. This theoretical consideration was reinforced both by the lack of an appreciable effect of 1.5 mM (or even higher concentrations) H 2 O 2 on yeast grown in the presence of ethanol or glycerol, and by the observed inhibition of the synthesis of ethanol promoted by H 2 O 2 . Normal values for the adenylic charge, ATP and inosine levels were reached at 5, 30 and 120 min, respectively, after removal of H 2 O 2 from the culture medium. The strong decrease in the ATP level upon H 2 O 2 treatment is an important factor to be considered for understanding the response of yeast, and probably other cell types, to oxidative stress.

Oxidative stress response to menadione and cumene hydroperoxide in the opportunistic fungal pathogen Candida glabrata

“…1A shows that LP cells of C.g.BG14 (wt) can resist up to 0.2 mM menadione and that this resistance is dependent on Cta1. Menadione is a cytotoxic quinone that generates superoxide and it has been shown that exposure to menadione induces the expression of S.c. and S.p.Cta1 (Nakagawa et al 1995, Osorio et al 2003. This result suggests that the superoxide generated by menadione is dismutated to H 2 O 2 , which is then reduced by the catalase.…”

Efficient RNA Polyuridylation by Noncanonical Poly(A) Polymerases

“…These data strongly suggest that the ability of tCid1 to incorporate uridylyl residues instead of adenylyl residues is specific to this polymerase. We next determined whether UTP could still out-compete ATP at physiologically relevant ratios, given that ATP is present in a 2-to 10-fold molar excess over UTP in vivo (3,31). tCid1 was incubated with (A) 15 and ATP in a 10-fold molar excess over UTP or with the combination of UTP, CTP, and GTP (Fig.…”

Regulatory Circuits of the AAA+ Disaggregase Hsp104

“…7D slow or fast branch on right is determined by the occupancy of NBD1 with ATP, which in turn depends on the levels of ATP and ADP as well as on the nucleotide state of NBD2. Under normal growth conditions, the ATP concentration in the yeast cytosol is in the low millimolar range whereas the ADP level is ϳ5-10 times lower (40). The concentration of ADP is relevant because ADP is a competitive inhibitor (41) and thus increases the apparent K m for ATP.…”