Inhibition by homogentisic acid of polypeptide synthesis in rat liver and brain ribosomal systems

Add time:07/30/2019    Source:sciencedirect.com

The finding in a previous study from this laboratory that homogentisic acid inhibits protein synthesis in microsomal systems from mammalian tissues led to the present investigation on the possible mechanism of this inhibition. It was determined that homogentisic acid inhibits the transfer of amino acid from aminoacyl-tRNA to ribosomal protein but has no effect on the formation of aminoacyl-tRNA. Homogentisic acid inhibited equally poly U-dependent polyphenylalanine synthesis and ribosomal protein synthesis. Ribosome-dependent peptidyl puromycin synthesis was not affected. The inhibition was partially reversed by pH 5 enzyme fraction and by a partially-purified transferase preparation. On the basis of these observations it is suggested that homogentisic acid inhibits protein synthesis by interfering with one or more of the transferase-dependent reactions in polymerization. The inhibitory effect of homogentisic acid was not dependent on Mg2+ or cofactors, and was shared by analogous compounds having the 2,5-dihydroxyphenolic structure.

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