Faculty Bibliography

(1) Changes during development in the levels of proteinases and peptidases were measured in brain homogenates. At all ages di- and tripeptidase levels were 7-15-fold higher than proteinase activity. (2) Cathepsin A and D and neutral proteinase activity first decreased (during the 5 days before birth) and then increased (primarily during the first 10 days after birth) in development. The total enzyme content per unit weight of brain did not change greatly after 10 days, although specific activity fell owing to an increase in protein in older animals. (3) The developmental pattern of activities or peptidases measured with Leu-Gly and Leu-Gly-Gly and of arylamidases measured with Arg- and Arg-Arg-beta-naphthylamides was similar to that of proteinases. Total and specific activities increased rapidly after birth; then total activity did not change and specific activity decreased. (4) The proteinase content of tissue fractions (nuclear and lysosomal-mitochondrial) similarly reached a maximal peak in the rapid growth phase of the brain. (5) The decrease of hydrolytic activity after 10 days of age seems to parallel a decrease in the rates of protein breakdown in vivo, showing parallel behavior with decreasing protein turnover. In contrast, during the first 10 days of life protein turnover and calculated rate of protein breakdown in vivo decrease while the level of hydrolytic enzymes increases

The uptake of amino acids into slices of adult and newborn mouse brain was studied in relation to Na+ flow. (1) The level of Na+ and K+ incubated slices of brain depends on the ionic composition of the incubation medium. The intracellular levels of Na+ in adult tissue are below, in fetal tissue above, Na+ levels in the medium used. Rapid net flow into or out of the tissue can be achieved by transferring slices into media of higher or lower Na+ content. (2) Under conditions of net Na+ inflow, the influx of all amino acids tested increased; under conditions of net Na+ outflow, the influx of all amino acids decreased, as compared to slices in ionic equilibrium. The absolute levels of Na+ in the tissue under the experimental conditions had little effect on amino acid uptake. The stimulatory effect of Na+ inflow and the inhibitory effect of Na+ outflow could be observed at all developmental stages--in adult, newborn, and fetal tissue. (3) We conclude that ion movements influence metabolite transport; these effects are smaller in the absence of fully developed ion pumps. The direction of the net ion flow does not seem to be the main determinant: active accumulation occurred both in adult and in fetal brain, although the tissue-to-medium Na+ gradients were in opposite directions; in addition, amino acid inflow occurred in the presence of Na+ outflow