Control of Protein Synthesis in Mammalian Tissues through Changes in Ribosome Activity

We have measured the rate of protein synthesis per unit of ribosomes in several tissues of intact animals in the fed and fasted state. The technique utilized measured the rate of incorporation of radioactive lysine into protein and was designed to produce relatively constant intracellular specific activities which were taken into account in calculating absolute rates of lysine incorporation. In animals fed ad libitum but growing at different rates, the rates of protein synthesis per unit of ribosomes in liver and muscle varied directly with growth rate and ranged in liver from 2.4 to 9.1 mµmoles of lysine incorporated per mg of RNA per min and in muscle from 1.1 to 3.9. Rates in brain and testis were variable, from 0.8 to 5.6 and 0.4 to 2.7, respectively, but did not correlate with growth rate. The rate in the Dunning ascites tumor was 1.0 to 1.5, which is consistent with the doubling time of these cells. During a 3½ day fast, rates fell to one-half to one-quarter of the fed value in liver and muscle, but were maintained in the tumor (until its terminal phase of growth in the animal), and appeared, on the basis of limited data, also to be maintained in brain and testis. These responses to fasting correlate well with the rapid loss of protein from liver and muscle during fasting and the maintenance of tissue protein in the latter three tissues. To identify the mechanisms that modulate the synthesis rate per unit of total ribosomes, we measured, in the liver, the proportion of ribosomes incorporated in polyribosomes (and hence active in synthesis) and also calculated the synthesizing activity of these ribosomes. The variations in synthesis among fed animals were due entirely to changes of polyribosome activity. These appeared to be due to alterations in soluble factors rather than in the ribosomes themselves. In fasted animals the decrease in protein synthesis in the liver was due to roughly equal decreases in ribosome content, polyribosome activity, and the proportion of ribosomes in polyribosomes.