Amino acid conferred protection against melphalan interference with melphalan therapy by L-leucine, a competitive substrate for transport.
Melphalan uptake by L1210 leukemia cells obtained from tumor bearing mice is reduced to one-third of control by physiological concentrations of L-leucine. Kinetic analysis revealed that melphalan and leucine compete for transport carrier sites. Administration of leucine with optimal therapeutic doses of melphalan to tumor bearing mice negated the efficacy of the drug.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism*; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice
D002352:Carrier Proteins; D007930:Leucine; D008558:Melphalan