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EFFECT OF THE ANTIBIOTIC, CYCLOHEXIMIDE, ON THE METABOLISM AND GROWTH OF SACCHAROMYCES PASTORIANUS
Author(s) -
Coursen Bradner W.,
Sisler Hugh D.
Publication year - 1960
Publication title -
american journal of botany
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.218
H-Index - 151
eISSN - 1537-2197
pISSN - 0002-9122
DOI - 10.1002/j.1537-2197.1960.tb14904.x
Subject(s) - cycloheximide , biology , biochemistry , toxicity , metabolism , yeast , glutamine , protein biosynthesis , amino acid , chemistry , organic chemistry
Coursen, B. W., and H. D. Sisler (U. Maryland, College Park.) Effect of the antibiotic, cycloheximide, on the metabolism and growth of Saccharomyces pastorianus. Amer. Jour. Bot. 47(7): 541–549. Illus. 1960.—Studies were made of the toxicity of cycloheximide and certain of its derivatives to Saccharomyces pastorianus Hansen. The ED 50 values for cycloheximide, its semicarbazone derivative and its oxime derivative are 0.018, 0.37, and 12.0.p.p.m., respectively. In auxanographic and liquid culture tests involving 160 organic and biochemicals, only certain methylated ring ketones and vitamin A alcohol or acetate showed appreciable antagonistic activity to the toxicity of cycloheximide. Yeast cells exposed to 3.16 p.p.m. of cycloheximide and incubated for 30 min. with uniformly labeled 14 C glucose remove about 10% less activity from the medium than untreated cells. Measurements of radioactivity in compounds extracted from cells with 80% ethanol showed the presence of appreciable activity in the glutamine from untreated cells but no measurable activity in this compound from treated cells. Activity in glutamic acid from treated cells was reduced while activity in alanine and aspartic acid was increased when compared with the activity in these compounds from untreated cells. There were other differences, also, especially in the levels of activity in organic phosphorus compounds, but, in many cases, the activity in compounds from treated cells was similar to that in the corresponding compounds from untreated cells. It is possible that the antibiotic interferes with the metals involved in the enzymatic reaction leading to the synthesis of glutamic acid and glutamine or it may act as an inhibitory analog in the synthesis of these or similar compounds. The apparent interference of cycloheximide with the formation of a CO‐NH bond in the synthesis of glutamine suggests also that peptide bond formation in protein synthesis may be similarly affected. A block of glutamine synthesis by cycloheximide may be sufficient to account for the toxicily of the antibiotic, but the failure of exogenous sources of glutamine to reverse the toxicity indicates that other reactions in cell metabolism may be as sensitive to cycloheximide as the synthesis of glutamine.