Abstract

The mechanism by which sodium fluoride and cycloheximide inhibit protein synthesis in the rabbit reticulocyte complete, cell-free system has been investigated. Both compounds have been found to inhibit the initiation of new chains on ribosomes. Studies of the rate of amino acid incorporation indicate that cycloheximide also inhibits incorporation into nascent chains that were initiated in intact cells and remain attached to ribosomes during their isolation. Sodium fluoride was found to have no apparent effect on the rate of incorporation into these previously initiated nascent chains, but to cause an apparent breakdown of polysomes to single ribosomes in intact cells. These 80 s ribosomes isolated from sodium fluoride-treated reticulocytes actively incorporate amino acids in the cell-free system and exhibit other properties that indicate they are similar or identical to monomeric ribosomes isolated from untreated cells. These observations are interpreted to indicate a sodium fluoride-sensitive reaction related to the initiation of new peptide chains on ribosomes. The sodium fluoride inhibition of this reaction may bring about the increase in the proportion of monomeric ribosomes because of a failure to re-form polysomes.

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