In vivo rate of translation by ribosomes of normal and regenerating liver.

Abstract Protein synthesis in normal and regenerating mouse livers was compared 36 hours after surgical removal of two-thirds of the liver. At that time, the total protein content of the remaining tissue had increased by 30 % and continued to grow at a rate greater than 20 % per day. Total DNA did not change until the end of the second day after the operation. Total RNA increased in parallel with protein, so that although its total amount per cell was larger (up to the time when the enlarged cells divided) its concentration, and that of deoxycholate-sedimentable RNA (relative to protein or wet weight), remained the same. The in vivo rate of incorporation of trace amounts of l-[1-14C]leucine into liver protein was 60 % higher in the regenerating livers than in the normal ones. A small portion of this increased incorporation could be explained by an increase of approximately 10 % in the relative proportion of ribosomes occurring as polyribosomes, but most of the difference reflected a more efficient labeling of the newly synthesized protein per ribosome unit in polyribosomes. However, the in vivo rate of translation by polyribosomes of normal and regenerating livers was found to be the same. Key to this conclusion was the measurement of the rate of translation by two different procedures, neither of which depended on the measurement of the specific radioactivity of the precursor. In the first one, the animals were flooded with massive amounts of radioactive leucine in an attempt to expand the free leucine pool to the point where endogenous sources become negligible. Extrapolation of these results showed normal and regenerating polyribosomes to incorporate 0.95 mole of leucine per s per mole of ribosomes. In the other procedure, nascent chains were labeled in vivo with trace or massive doses of radioactive leucine, and transit times were calculated from the rate at which they were finished and released. The transit time was found to be the same, 1.06 min, in the normal and regenerating situations.