Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo

Fetal growth and development are dependent upon the adequate provision of oxygen and substrates from the maternal circulation. The need for amino acids is related to protein synthesis, interconversion to other substrates, and oxidation. Amino acids cross the placenta by active transport systems, and their concentrations in the fetus are higher than in the mother. In addition, most amino acids are extensively metabolized within the placenta, and, for some nonessential amino acids, placental synthesis has been demonstrated in chronically catheterized fetal lambs. Interorgan cycling between the fetal liver and placenta has been hypothesized for nonessential amino acids like glycine and serine. Amino acids are oxidized within the fetal tissues, particularly in liver and muscle, with differences between amino acids and in relation to metabolic state. In human pregnancies, maternal-fetal transfer rates have been investigated in vivo by stable isotope methodologies performed at fetal blood sampling. The transfer rate of nonessential amino acids like glycine is significantly lower than for essential amino acids like leucine, confirming glycine synthesis in the fetoplacental unit also in human pregnancies. Moreover, when a steady state model is applied, the fetal-maternal ratio for [1-(13)C]leucine is significantly reduced in pregnancies associated with intrauterine growth restriction, reflecting a decrease in leucine placental transfer and/or an increase in protein catabolism in the fetoplacental unit. This reduction is proportional to the degree of severity of intrauterine growth restriction but is significant also in those intrauterine growth-restricted fetuses with normal oxygenation and acid-base status.