Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems.
The livR locus, which leads to a trans-recessive derepression of branched-chain amino acid transport and periplasmic branched-chain amino acid-binding proteins, is responsible for greatly increased sensitivity toward growth inhibition by leucine, valine, and serine and, as shown previously, for increased sensitivity toward toxicity by branched-chain amino acid analogues, such as 4-azaleucine or 5',5',5'-trifluoroleucine. These phenotypes are similar to those of relA mutants; however, the livR mutants retain the stringent response of ribonucleic acid synthesis. However, an increase in the rate of transport or in the steady-state intracellular level of amino acids in the livR strain cannot completely account for this sensitivity. The ability of the LIV-I transport system to carry out exchange of pool amino acids for extracellular leucine is a major factor in leucine sensitivity. The previous finding that inhibition of threonine deaminase by leucine contributes to growth inhibition is confirmed by simulating the in vivo conditions using a toluene-treated cell preparation with added amino acids at levels corresponding to the internal pool. The relationship between transport systems and corresponding biosynthetic pathways is discussed and the general principle of a coordination in the regulation of transport and biosynthetic pathways is forwarded. The finding that the LIV-I transport system functions well for amino acid exchange in contrast to the LIV-II system provides another feature that distinguishes these systems in addition to previously described differences in regulation and energetics.
D001693:Biological Transport, Active / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism*; D005796:Genes; D007532:Isoleucine / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D012694:Serine / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism; D013913:Threonine Dehydratase / Q000378:metabolism; D014633:Valine / Q000378:metabolism*
D007532:Isoleucine; D013912:Threonine; D012694:Serine; D013913:Threonine Dehydratase; D007930:Leucine; D014633:Valine