Transfer of Cyst(e)ine and Methionine across the Human Placenta

Abstract

ExtractAfter 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. SpeculationCyst(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-activating 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 a-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 iS'-adenosylmethionine, a compound involved in important synthetic reactions.

Maternal-Fetal Cyst(e)ine Transfer

“…In contrast, most other amino acids are present in higher concentrations in fetal plasma than in maternal plasma [5][6][7], The mechanism by which cyst(e)ine transfer across the placenta is limited is not known. In order to gain further insight into the factors that might limit cyst(e)ine transfer across the placenta, we first confirmed the original ob servation of Gaull et al [4], Second, we con firmed that the placenta does concentrate cyst(e)ine. Third, we used a rat model to eval uate the effects of excess cysteine on mater nal-fetal cyst(e)ine transfer and to estimate the capacity of maternal rats and their respec tive fetuses to metabolize excess cyst(e)ine over a short period of time.…”

“…Gaullet al [4] observed that cysteine injected into human mothers at the time of voluntary pregnancy termination was not taken up in significant amounts by fetal organs. These authors suggested that the rapid uptake of cyst(e)ine by fetal tissues was, therefore, not the cause of the reported low fetal plasma cyst(e)ine concentrations.…”

“…GaulI et al [4] made the original observation that the concentration of cyst(e)ine (referring in the following to the mixture, in any proportion, of the sulfhydryl form of this compoundcysteine -and the disulfide form -cystine) in fetal plasma is equal to or less than the con centration of cyst(e)ine in maternal plasma. In contrast, most other amino acids are present in higher concentrations in fetal plasma than in maternal plasma [5][6][7], The mechanism by which cyst(e)ine transfer across the placenta is limited is not known.…”

Hepatic Metallothionein as a Source of Zinc and Cysteine during the First Year of Life

“…Unlike other amino acids, the concentration of cysteine is lower in the fetal than the maternal circulation (28). Despite the low fetal plasma concentration of cysteine, high metallothionein concentrations corresponding to the hepatic zinc concentrations imply that adequate substrate is available for metallothionein synthesis.…”

Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract

“…In addition, it also serves as a precursor of glutathione, a major cellular antioxidant, as well as CoA, taurine, and inorganic sulfur. Several tissues in the body are capable of cysteine synthesis (14), which is why cysteine is considered nutritionally dispensable. However, increasing evidence that oxidant stress is linked to many disease pathologies and aging has focused attention on the antioxidant functions of cysteine and its product, glutathione, leading some to suggest that cysteine is a conditionally indispensable dietary nutrient (15)(16)(17).…”