Ontogeny of L-Alanine Uptake in Plasma Membrane Vesicles from Rat Liver

Abstract

Alanine uptake into liver plasma membrane vesicles was studied at different stages of postnatal rat development. Before weaning, alanine hepatic uptake showed lower values for the global K, than after weaning (0.34,0.77, 1.45, and 1.61 mM for I-, 1 5 , and 28-d-old and adult rats, respectively). Alanine uptake capacity increased progressively until reaching maximum values in the adult state (values for V,,,: 0.078,0.199,0.317, and 0.613 nmol alaninelmg protein13 s for I-, 1 5 , and 28-d-old and adult rats, respectively). These results seem to point to a prevalence of a high affinity, low capacity alanine transport component (traditionally assumed to be attributable to system A) in newborn and suckling rats, in agreement with our previous results on isolated hepatocytes (Martinez-Mas JV, Casado J, Felipe A, Marin JJG, Pastor-Anglada M: Biochem J 293: 819-824, 1993). The suckling-weaning developmental transition seems to play a role in establishing the pattern of adult hepatic alanine transport characterized by a higher capacity but a lower affinity (because most alanine is taken up by system ASC) inasmuch as K, values show a 100% increase after weaning, although V, , , values continue to increase steadily until the adult age. Amino acid transport and utilization during postnatal development have not been extensively studied in spite of their role in sustaining growth. Amino acids are mainly used for anabolic purposes, such as protein accretion (1) with rates even higher than in the adult (2-4) or purine and pyrimidine biosynthesis (5). Moreover, typical gluconeogenic amino acids such as alanine play only a minor part as substrates for glucose production along the whole suckling period (1, 6). This lack of information is particularly noticeable regarding the sucklingweaning developmental transition, a period of trascendental metabolic changes in which carbohydrate and lipid metabolism are very well studied (7-9). Furthermore, most of the studies on amino acid transport during development have been performed on cultured hepatocytes from protease-treated livers (10-12), with some controverted results. Different approaches applied to amino acid transport during development are quite scarce (13). Recently, we have reported the kinetic study of alanine transport in freshly isolated hepatocytes from rat fetuses and neonates by a less injurious methodology (14). In that report, it was shown that, in fetal and neonatal hepatocytes,