Inhibition of the reductive activation of a valyl-tRNA synthetase from yeast by unsaturated fatty acids and associated observations on newly found lipophilic substances from yeast.

The reductive activation of a valyl-tRNA synthetase from yeast is strongly inhibited by 1-30 microM unsaturated fatty acids, and the inhibition is antagonized by 10-100 microM saturated fatty acids. Diethylstilbestrol also inhibits the activation. The possibility that unesterified palmitoleic and oleic acids are bona fide regulatory effectors is supported by a dramatic inverse relation between their cellular content and the growth rate of commercial bakers' yeast. An increase in the ratio of unsaturated to saturated acids with slowing growth in a laboratory strain, S288C, also supports the regulatory hypothesis. The free fatty acids are extracted into slightly acidified 50% alcohol together with traces of numerous novel lipophilic substances. One of these is suggested to function as a cofactor in conjunction with a heat-stable polypeptide that activates valyl-tRNA synthetase.