Free polyribosomes, protein synthesis

Protein synthesis can be carried out by ribosomes free in the cytosol. In eukaryotes, ribosomes also carry out protein synthesis while bound to the surface of the endoplasmic reticulum. In addition, a given mRNA molecule usually has more than one active ribosome translating it into protein an assembly of several ribosomes on a single mRNA is called a polyribosome, or polysome for short. 

After establishing that L-tryptophan alone stimulated overall hepatic protein synthesis, it became important to determine which proteins were involved. Increased synthesis of albumin due to L-tryptophan was reported by Rothschild et al.65 and by Jorgensen and Majumdar.47/18 The latter investigators also reported that tryptophan increased the synthesis of transferrin, fibrinogen, and ferritin. Thus, extracellular as well as intracellular proteins that are synthesized by the liver were affected by L-tryptophan. Furthermore, it was demonstrated that after L-tryptophan administration, both free and membrane-bound polyribosomes of the liver showed a shift toward heavier aggregation, more marked for free polyribosomes than for membrane-bound polyribosomes.62 Also, in vitro protein synthesis revealed a greater increase with free polyribosomes than with membrane-bound polyribosomes of the livers of tryptophan-treated animals in comparison with similar fractions of livers of control animals. 

Moja et al.57 treated rats with cycloheximide, an inhibitor of protein synthesis, and then fed a tryptophan-free mixture. The cycloheximide treatment largely prevented the marked decrease of plasma tryptophan (total and free). These data supported the hypothesis that protein synthesis was the mechanism through which the ingested tryptophan-free mixture decreased blood tryptophan levels. However, this interpretation was not consistent with the findings of Wunner et al.58 and Sidransky et al.,59 who observed a low rate of polyribosome formation and low incorporation of labeled amino acids in the livers of rodents previously fasted and then acutely fed a tryptophan-free amino acid mixture. 

Compared with some of the other mycotoxins such as aflatoxin, the trichothecenes do not appear to require metabolic activation to exert their biological activity.50 After direct dermal application or oral ingestion, the trichothecene mycotoxins can cause rapid irritation to the skin or intestinal mucosa. In cell-free systems or single cells in culture, these mycotoxins cause a rapid inhibition of protein synthesis and polyribosomal disaggregation.35 47 50 Thus, we can postulate that the trichothecene mycotoxins have molecular capability of direct reaction with cellular components. Despite this direct effect, it is possible to measure the toxicokinetics and the metabolism of the trichothecene mycotoxins. 

De Luca and his associates have studied the effects of vitamin A on protein synthesis in the intestinal mucosa and have observed that vitamin A interferes with the biosynthesis of protein by membrane-bound polyribosomes, but not with the biosynthesis of proteins by free polyribosomes [115]. 

In the cell-free systems prepared from hypophysectomized rats, ribosomes lose their capacity to participate in protein synthesis, possibly by dispersion of the polyribosome system into smaller units. Growth hormone is thought to act on protein synthesis in hypophysectomized animals by stimulating amino acid uptake and indirectly increasing the production of messenger RNA. 

Siegel, F.L., Aoki, K. and Colwell, R.E. (1971), Polyribosome disaggregation and cell-free protein synthesis in preparations from cerebral cortex of hyper-phenylalaninaemic rats. J. Neurochem., 18,537. 

Throughout the ribosome cycle, dynamic protein-mRNA interactions are functionally important in the initiation, elongation, and termination of polypeptide synthesis. In addition, more stable associations between proteins and mRNAs have been observed, particularly in eukaryotic cells. These messenger ribonucleoprotein complexes (mRNPs) occur both in polyribosomes and free in the cytosol, some of the latter being either temporarily or permanently unavailable for translation. Thus, protein-mRNA interactions contribute to the efficiency with which mRNAs are translated. 

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