Metabolic activity and intracellular distribution of nucleic acid phosphorus in regenerating liver

Abstract The specific activity-time curves for the various liver nucleic acids were determined within a 6-hr. period from 58 to 64 hr. after partial hepatectomy in mice using P 32 as the tracer. The nuclear, supernatant, ultramicrosomal, and microsomal RNA's are listed in the order of decreasing specific activities. The protein and phospholipide phosphorus specific activities increased rapidly during the first hour, and all, with the exception of those from nuclei that were lower, were almost equal to the IP specific activity 6 hr. after P 32 injection. A study of the quantitative distribution of RNA revealed that about 40% of the cell RNA in the 60-hr. regenerating liver is associated with the microsome fraction. Only about 5–10% could be accounted for by each of the RNA's of the other fractions. Assuming the condition of the steady state and metabolic homogeneity of the various nucleic acid phosphorus pools, equations representing different metabolic schemes were tested. It was shown that the data were in reasonable agreement with a metabolic scheme according to which M-RNA is formed from N-RNA at the rate of 3.4%/hr., and N-RNA appears at the rate of 24 and 34%/hr. from IP and M-RNA, respectively. Limiting fractional rates for the appearance of the various RNA's were calculated using the liver inorganic phosphorus specific activity-time curve in place of that of the immediate precursor; these were 1–2% and 25%/hr. for cytoplasmic and nuclear RNA, respectively. This fractional renewal rate for N-RNA is much greater than most values reported in the literature and, even so, must be considered a limiting minimum value. It seemed unjustified to assume the steady-state condition during the kinetic study for the rates of reactions leading to DNA on the basis of the shape of its specific activity-time curve and on the morning-afternoon differences in the 1-hr. relative specific activity. Therefore, metabolic reactions involving DNA were not tested. An equation was developed to test whether the U fraction is a mixture of particles containing M- and S-RNA. The calculated specific activities from approximately a 50:50 mixture of S- and M-RNA were in fairly good agreement with the observed values of U-RNA.