Branched-chain amino acids overcome cycloleucine growth inhibition in B12 and non-B12-requiring microorganisms.
Because cycloleucine (CL) inhibits methionine, and probably B12, we studied CL activity in some B12 or methionine dependent microorganisms to determine whether methionine or other amino acids are targeted by CL. We found that branched-chain amino acids, valine in particular, effectively annulled CL growth inhibition, whereas B12 was ineffective. alpha-Ketoisovalerate was the only intermediate in pathways of branched-chain amino acids catabolism that overcome CL toxicity; propionate, methylmalonate, succinate, alpha-ketoisocaproate and alpha-ketoglutarate were inactive by themselves or in combination. This study suggests that CL antagonizes the action of not only B12 and methionine but also branched-chain amino acids. Results seem comparable to those with B12-deficient fruit bats having neurologic involvement.
Baker
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H
Department of Preventive Medicine and Community Health, New Jersey Medical School, Newark.
Frank
O
O
DeAngelis
B
B
Baker
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E
D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D003515:Cycloleucine / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005056:Euglena gracilis / Q000187:drug effects / Q000254:growth & development; D056890:Eukaryota / Q000187:drug effects / Q000254:growth & development; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors*; D008715:Methionine / Q000037:antagonists & inhibitors*; D014805:Vitamin B 12 / Q000037:antagonists & inhibitors*
D000596:Amino Acids; D006131:Growth Inhibitors; D003515:Cycloleucine; D008715:Methionine; D014805:Vitamin B 12