Mechanism of D-cycloserine action: transport systems for D-alanine, D-cycloserine, L-alanine, and glycine.
The accumulation of d-alanine, l-alanine, glycine, and d-cycloserine in Escherichia coli was found to be mediated by at least two transport systems. The systems for d-alanine and glycine are related, and are separate from that involved in the accumulation of l-alanine. d-Cycloserine appears to be primarily transported by the d-alanine-glycine system. The accumulation of d-alanine, glycine, and d-cycloserine was characterized by two line segments in the Lineweaver-Burk analysis, whereas the accumulation of l-alanine was characterized by a single line segment. d-Cycloserine was an effective inhibitor of glycine and d-alanine accumulation, and l-cycloserine was an effective inhibitor of l-alanine transport. The systems were further differentiated by effects of azide, enhancement under various growth conditions, and additional inhibitor studies. Since the primary access of d-cycloserine in E. coli is via the d-alanine-glycine system, glycine might be expected to be a better antagonist of d-cycloserine inhibition than l-alanine. Glycine and d-alanine at 10(-5)m antagonized the effect of d-cycloserine in E. coli, whereas this concentration of l-alanine had no effect.
D000409:Alanine / Q000378:metabolism* / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis; D001322:Autoanalysis; D001386:Azides / Q000494:pharmacology; D001692:Biological Transport; D002247:Carbon Isotopes; D002701:Chloramphenicol; D002852:Chromatography, Ion Exchange; D002854:Chromatography, Paper; D003470:Culture Media; D003523:Cycloserine / Q000378:metabolism / Q000494:pharmacology*; D003864:Depression, Chemical; D004926:Escherichia coli / Q000032:analysis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000378:metabolism* / Q000494:pharmacology; D009995:Osmosis; D013237:Stereoisomerism; D013696:Temperature; D013997:Time Factors
D000596:Amino Acids; D001386:Azides; D002247:Carbon Isotopes; D003470:Culture Media; D002701:Chloramphenicol; D003523:Cycloserine; D005947:Glucose; D000409:Alanine; D005998:Glycine