SERINE AND GLYCINE TRANSPORT IN FETAL OVINE HEPATOCYTES

Abstract

43 Serine (ser) and glycine (gly) are poorly transported across the placenta from the mother to the fetus. Although we have shown that the fetal liver is an important primary site of fetal ser synthesis for the unique fetal metabolism of ser and gly, the regulation of this unique fetal ser and gly metabolism is uncertain. The goal of this study was to characterize ser and gly transport in primary cultures of fetal ovine hepatocytes. Transport was determined after primary culture of hepatocytes from term (≈135 days) fetal lambs using sodium free or sodium containing KRP and the appropriate U-14C labeled amino acid after overnight culture. (Table) At 300µM concentrations, sodium dependent transport was inhibited by NEM (ser 36±9% and gly 37±2%) with similar inhibition by MeAIB. There was competitive inhibition of total gly transport by ser but not of ser transport by gly. Sodium free gly transport was higher in low glucose (1.1 mM) media (881±76) compared to high glucose (10 mM) media (510±60 p=0.004). Gly transport was inhibited by sarcosine. These data suggest that ser is primarily transported via system L and ASC in term fetal ovine hepatocytes while gly is transported primarily by system L with less of a contribution from ASC and gly. There is a contribution from system A to both ser and gly transport in term fetal ovine hepatocytes. The predominance of ser transport over gly at physiologic concentrations suggests that inward cellular amino acid transport of ser and gly is not likely to be a regulatory mechanism that would favor ser biosynthesis in fetal ovine hepatocytes except in conditions that would favor sodium free transport.TABLE