The Effect of Puromycin on the Developmental and Adaptive Formation of Tryptophan Pyrrolase*

  • ANDREW M. EMETH, S Z G, DE LA HABA
  • Published 2001

Abstract

Earlier investigations of glycogen metabolism in developing guinea pig liver unexpectedly revealed that glucose 6-phosphatase activity is absent in the fetus. Additional studies of guinea pig and rat liver showed that glucose 6-phosphatase activity first appears at term and increases rapidly to adult levels immediately after birth (1, 2). Since this finding, many enzymes that subserve special liver functions have been shown to have this same pattern of development. One of these enzymes is tryptophan pyrrolase (3, 4). Tryptophan pyrrolase activity is absent in fetal liver and rises rapidly to adult values after birth (5). The activity of this enzyme can be increased in the adult many fold in a few hours by injection of L-tryptophan (6). This responsiveness to L-tryptophan is absent or very small in the fetus and develops in the new-born simultaneously with the increase of tryptophan pyrrolase activity to adult levels (3, 5). We have been interested in elucidating the mechanisms by which tryptophan pyrrolase activity is increased in the new-born, and in the adult after injection of L-tryptophan. The experiments reported here were planned to determine whether these increases depend upon the synthesis of additional enzyme molecules from amino acids or the activation of protein precursors. To approach this problem we have utilized the compound, puromycin, an antibiotic which blocks the synthesis of protein from amino acid (7, 8). With repeated injections of puromycin it was possible to inhibit almost completely the incorporation of valineCl4 into liver protein for many hours. It follows that under such conditions any increase in tryptophan pyrrolase activity must be due to the activation of preformed protein. We found that the normal developmental increase in tryptophan pyrrolase activity in the new-born is blocked completely by puromycin. The adaptive increase in the adult can be inhibited approximately 70%. Thus, we have concluded that the normal developmental increase in tryptophan pyrrolase activity after birth probably depends entirely upon the formation of new enzyme molecules from amino acid, whereas the adaptive increase in enzyme activity in the adult after L-tryptophan injection is brought about partly by new enzyme formation and partly by the activation of pre-existing protein. The site of action of puromycin in blocking amino acid incorporation into protein was also studied, and the results are discussed.

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Cite this paper

@inproceedings{EMETH2001TheEO, title={The Effect of Puromycin on the Developmental and Adaptive Formation of Tryptophan Pyrrolase*}, author={ANDREW M. EMETH and S Z G and DE LA HABA}, year={2001} }