The role of amino acids in the regulation of hydrogen sulfide production during ultradian respiratory oscillation of Saccharomyces cerevisiae

We previously demonstrated that periodic H2S production during aerobic cont inuous culture of Saccharomyces cerevisiae resulted in ultradian respirator y oscillation, and that H2S production was dependent on the activity of sul fate uptake and the level of sulfite. To investigate the mechanism of regul ation of the sulfate assimilation pathway and of respiratory oscillation, s everal amino acids were pulse-injected into cultures during respiratory osc illation. Injection of sulfur amino acids or their derivatives perturbed re spiratory oscillation, with changes in the H2S production profile. Four maj or regulators of H2S production in the sulfate assimilation pathway and res piratory oscillation were identified: (1) O-acetylhomoserine, not O-acetyls erine, as a sulfide acceptor, (2) homoserine/ threonine as a regulator of O -acetylhomoserine supply, (3) methionine/S-adenosyl methionine as a negativ e regulator of sulfate assimilation, and (4) cysteine (or its derivatives) as an essential regulator. The results obtained after the addition Of DL-pr opargylglycine (5 muM and 100 muM) and cystathionine (50 muM) suggested tha t the intracellular cysteine level and cystathionine gamma -lyase, rather t han methionine/S-adenosylmethionine, play an essential role in the regulati on of sulfate assimilation and respiratory oscillation. Based on these resu lts and those of our previous reports, we propose that periodic depletion o f cysteine (or its derivatives), which is involved in the detoxification of toxic materials originating from respiration, causes periodic H2S producti on.