Ethanol Inhibition of Reticulocyte Protein Synthesis: The Role of Haem

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Abstract
Summary. Ethanol, in concentrations of 0.05–0.8 M, inhibited intact human and rabbit reticulocyte protein synthesis in the presence of iron-transferrin for endogenous haem synthesis. Associated with this effect there was a conversion of polyribosomes to monoribosomes and a decreased incorporation of radioactive leucine into nascent globin chains. When physiological levels of ethanol (0.05–0.1 M) were used, these effects were prevented by incubation with 50 μM haemin and reversed by removing the alcohol and reincubating with iron-transferrin or haemin. The polyribosomal disaggregation was also prevented by stopping ribosomal movement with 5 mM cycloheximide. Neither ATP nor GSH levels were altered in the presence of ethanol. When non-physiological levels of 0.8 M ethanol were used, haemin did not prevent the inhibition of protein synthesis. Likewise, in the rabbit reticulocyte cell-free lysate system containing haemin inhibition was noted at concentrations greater than 0.05 M ethanol. The polyribosomal disaggregation in reticulocytes incubated with 0.8 M ethanol was associated with decreased dissociation of monoribosomes into subunits. Similarly, when ribosomes were directly suspended cell-free in 0.1 or 0.8 M ethanol there was a decreased percentage of subunits. These results indicate that physiological concentrations of ethanol inhibit initiation of reticulocyte protein synthesis secondary to a block in haem synthesis. When intact cells are exposed to high non-physiological concentrations of ethanol the inhibition is secondary to decreased ribosomal dissociation. The cell-free lysate inhibition is also through this effect on ribosomal dissociation. This study supports the view that alcohol is a direct toxin to developing red cell precursors via its effect on mitochondrial haem synthesis. The physiological role of the decreased dissociation of monoribosomes into subunits is not yet clear.