Early Postnatal Intensification of Hepatic Accumulation of Amino Acids

Abstract

The liver of the fetal guinea pig was recently found not to concentrate several unmetabolizable model amino acids (1). This result seemed at first to represent an unusual, if not unique, discrimination against these substances. Our attention was brought, however, to the work of Nemeth and his associates, which showed that a number of characteristic enzymes of the liver appear to be absent in the fetus. These enzymes develop within the first day after birth, or the first day after artificial removal of the fetus from the fetal environment ((Z-10); cf. (11) and bibliographies of these papers). Further exploration of the matter of amino acid uptake shows that the transport deficiency of the liver of the fetal guinea pig concerns normal as well as artificial amino acids, and that a very rapid increase in the extent of amino acid concentration occurs during the first 24 hours after Pregnant guinea pigs near term were maintained on Rockland guinea pig pellets, with fresh lettuce every second or third day. When the opening of the pubic symphysis indicated that delivery was about 5 days away, 2.2 to 2.5 mg of l-aminocyclopentanecarboxylic acid-l-Cl4 (12), representing about 10 mc and dissolved in 1 ml of 0.9% NaCl, were injected subcutaneously in the scapular region. This procedure allowed several days for the amino acid to be distributed, with little loss of radioactivity because this amino acid is so slowly excreted (13). The animals reported in Table I, and two of those reported in the figures, were delivered by section; all the rest were permitted to deliver spontaneously, the time of separation from the maternal circulation being noted. The analyses designated as “zero time” were made on animals killed within minutes of birth or, in the two exceptional cases, immediately after removal by section about 1 day before expected birth. Blood was taken from the heart of the animal under ether anesthesia. After the animal was killed by a blow on the head, the liver was removed, cut, and blotted to remove blood. It and the muscles of one thigh were weighed and then extracted with 10 ml of 0.01 N acetic acid for each gram by thorough grinding in a mortar. The resulting suspension was held for 3 minutes at 100” and then centrifuged to remove coagulated material. The plasma was deproteinized by adding 4 volumes of 10% trichloroacetic acid. The resulting extracts were analyzed for glycine by the method of Alexander, Landwehr, and Seligman (14) as modified by Christensen, Riggs, and Ray (15). Radioactivity was determined on 0.2-ml portions of the extracts added