Transfer of cyst(e)ine and methionine across the human placenta.

Abstract

Extract: After intravenous loads in pregnant women, L-methionine, L-leucine, and L-ornithine were transferred from maternal to fetal plasma against a two- to threefold difference in initial concentration. Cyst(e)ine is unique among the free amino acids of plasma in that its basal concentration in maternal plasma was equal to or greater than that in fetal plasma. Furthermore, after intravenous loads with L-cystine or L-cysteine, total cyst(e)ine (cystine and cysteine) was transferred less readily to the fetal plasma. Although the concentrations of cystine in the fetal plasma continued to rise in the face of rapidly falling concentrations of cystine in the maternal plasma, at no time during the experiment did the concentration of cystine in fetal plasma exceed that in the maternal plasma. When D-cystine was administered intravenously to a mother, in amounts equimolar with L-cystine, the transfer of D-cystine was not measurable. Speculation: Cyst(e)ine is the end-product of the transsulfuration pathway, which transfers the sulfur from the 4-carbon skeleton of methionine to the 3-carbon skeleton of serine. Methionine-actvating enzyme, the first enzyme on this pathway, is inhibited by cyst(e)ine [2, 5, 20]. It is also allosteric [19], a characteristic often associated with negative feedback inhibition. Cystathionase, which cleaves cystathionine to cysteine and α-ketobutyrate and is the last enzyme on this pathway, is absent from the liver and brain of the human fetus. Therefore, we postulate that the special mechanism for the transfer of cyst(e)ine across the human placenta is an adaptation to control the transfer of sufficient maternal cyst(e)ine for synthesis of protein and glutathionine without undue inhibition of the activation of methionine to S-adenosylmethionine, a compound involved in important synthetic reactions.