Metabolism of D-serine in Escherichia coli K-12: mechanism of growth inhibition.
Without significant killing, d-serine at concentrations greater than 50 mug/ml inhibits growth in minimal media of mutants of Escherichia coli K-12 unable to form d-serine deaminase. The mutants eventually recover at lower concentrations. There is no evidence of d-serine toxicity in rich media. Toxicity is partially reversed by l-serine. d-Serine does not interfere with l-serine activation, one-carbon metabolism, or (Cronan, personal communication) formation of phosphatidylserine. Pizer (personal communication) finds, however, that it is a powerful feedback inhibitor of the first enzyme of l-serine biosynthesis. In the presence of l-serine, the residual toxicity is largely and noncompetitively over come by pantothenate, indicating that d-serine inhibits growth by affecting two targets: pantothenate biosynthesis and l-serine biosynthesis. l-Serine causes transient growth inhibition in E. coli K-12. Contaminating l-serine in d-serine preparations contributes to the d-serine inhibitory response.
D001426:Bacterial Proteins / Q000096:biosynthesis; D002247:Carbon Isotopes; D002474:Cell-Free System; D004926:Escherichia coli / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism; D012695:L-Serine Dehydratase / Q000096:biosynthesis; D009154:Mutation; D010205:Pantothenic Acid / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism* / Q000494:pharmacology; D013237:Stereoisomerism; D014316:Tritium
D001426:Bacterial Proteins; D002247:Carbon Isotopes; D014316:Tritium; D010205:Pantothenic Acid; D012694:Serine; D012695:L-Serine Dehydratase; D007535:Isomerases