Control of hepatic protein synthesis. Differential effects of ATP levels on the initiation and elongation steps.

The effect of nucleotide energy levels in vivo on the different steps of protein synthesis has been studied. Hepatic anoxia was induced by interrupting the blood portal-vein flow. At 5 min of anoxia ATP fell to 59% of the control values and the amino acid incorporation into protein was inhibited by more than 70%. This strong inhibition was not paralleled by polyribosomal breakdown. On the contrary, when fasted rats were used, at 5 min of anoxia the ribosomal state of aggregation was found to increase. Longer periods of anoxia resulted in a further decrease in triphosphonucleoside content and polyribosomal breakdown. Based on these results and other reports from the literature it is concluded that the Km for the GTP of the peptide-chain-elongation mechanism must be higher than the Km of the initiation step. This finding implies that variations of nucleotide levels in vivo within the physiological range may control protein synthesis at the elongation step without apparent changes in the polyribosomal profiles.