Effects of chloramphenicol isomers and erythromycin on enzyme and lipid synthesis induced by oxygen in wild-type and petite yeast.
The synthesis of mitochondrial enzymes induced by exposure of anaerobically grown, lipid-depleted Saccharomyces cerevisiae to oxygen is inhibited by d(-)-threo-chloramphenicol and erythromycin. The concentration of these antibiotics required to cause 50% inhibition of this synthesis is less than 1 mm; this is also approximately the concentration required to inhibit by the same amount mitochondrial protein synthesis in situ. The synthesis of unsaturated fatty acids, ergosterol, and phospholipid induced by aeration is inhibited by d(-)-threo-chloramphenicol at high concentrations (12 mm) but is unaffected by erythromycin. l(+)-threo-Chloramphenicol affects neither enzyme nor lipid synthesis and is without effect on mitochondrial protein synthesis in situ. All three compounds inhibit the oxidative activity of isolated mitochondria; the chloramphenicol isomers also inhibit phosphorylation. In a euflavine-derived petite mutant, lacking mitochondrial protein synthesis and respiration, aeration results in the normal development of lipid in the cells, but no synthesis of mitochondrial enzymes. d(-)-threo-Chloramphenicol does not inhibit lipid synthesis in these cells. Thus inhibition of mitochondrial protein synthesis with erythromycin or genetic deletion of mitochondrial protein synthesis results in loss of the capacity to synthesize enzymes during aeration. d(-)-threo-Chloramphenicol, as well as inhibiting induced enzyme formation, inhibits lipid synthesis induced by oxygen. It is unlikely that the latter effect of chloramphenicol is due to inhibition of energy production and transformation, to direct effects on lipid synthesis, or to an inhibition of mitochondrial protein synthesis. It is, however, an effect not shared with the l isomer.
D000693:Anaerobiosis; D002701:Chloramphenicol / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D004917:Erythromycin / Q000494:pharmacology*; D005228:Fatty Acids, Essential / Q000096:biosynthesis; D005650:Fumarates; D006836:Hydro-Lyases / Q000096:biosynthesis*; D007536:Isomerism; D008055:Lipids / Q000096:biosynthesis*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010743:Phospholipids / Q000096:biosynthesis; D014176:Protein Biosynthesis; D012440:Saccharomyces / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000096:biosynthesis*; D014807:Vitamin D / Q000096:biosynthesis
D005228:Fatty Acids, Essential; D005650:Fumarates; D008055:Lipids; D010743:Phospholipids; D014807:Vitamin D; D004917:Erythromycin; D002701:Chloramphenicol; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D006836:Hydro-Lyases