Induced Phenotypic Resistance to Valine in Mycobacterium pellegrino

Abstract

Valine coordinately increases the levels of three of the enzymes participating in the biosynthesis of isoleucine and valine in Mycobacterium pellegrino. The amount of valine required for end-product induction depends on the condition of the cells. Isoleucine inhibits the effect of valine. Acetohydroxy acid synthetase, the enzyme catalyzing the first common step in the biosynthesis of valine and isoleucine, is inhibited by valine. The induction effect of valine appears to be due to its ability to inhibit the activity of this enzyme, thus causing isoleucine deficiency, which in turn leads to derepression. This conclusion is supported by the fact that valine, under certain conditions, inhibits growth.

Intermediary metabolism of mycobacteria.

“…L-Valine inhibits acetohydroxy acid synthetase, the first common step in the biosynthesis of isoleucine and valine and, when added to the growth medium, inhibits the growth of M. tuberculosis H37Rv (9). On the other hand, in M. pellegrino valine coordinately increases the levels of acetohydroxy acid synthetase, dihydroxy acid dehydratase, and threonine deaminase, three of the enzymes participating in the biosynthesis of isoleucine and valine in the organism, and L-isoleucine inhibits the effect of valine (153). The inductive effect of L-valine appears to be due to its ability to inhibit the activity of acetohydroxy acid synthetase, thus causing isoleucine deficiency, which in turn leads to the derepression of the three enzymes.…”