Plasma-membrane transport of alanine is rate-limiting for its metabolism in rat-liver parenchymal cells

Abstract

In the last decade the metabolism of amino acids in liver parenchymal cells has been subjected to inten- sive research (reviewed in [ 11). The presence of spe- cific amino-acid transport systems in the parenchymal cell membrane has been demonstrated, both in whole cells [2-51 and in isolated plasma-membrane vesicles [6-81. The possible connection between the transport of an amino acid and its subsequent metabolism in the liver cell has so far received only little attention. The uptake of alanine by isolated rat-liver parenchymal cells was reported to be inhibited by ouabain, whereas metabolism of alanine was not affected under these conditions [3]. This observation prompted the con- clusion that transport of alanine at the level used (0.5 mM) is not rate-limiting for alanine metabolism [ 31. We have investigated the relationship between transport and metabolism of alanine in perifused rat- liver parenchymal cells. The perifusion system [9,10] combines the advantages of the use of homogeneous and purified cell suspensions with those of experi- mentation under true steady-state conditions at physiologically low substrate concentrations, thus resembling the in vivo situation, Our results, in con- trast to those in [3] show that in the physiological concentration range (0.2-0.5 mM) [ 11,121 the trans- location of alanine across the plasma membrane is rate-limiting for alanine metabolism in rat-liver paren- chymal cells. 2.