Fetal serine fluxes across fetal liver, hindlimb, and placenta in late gestation

Eleven studies of fetal serine fluxes were performed in chronically catheterized fetal lambs by continuous infusion of [1-¹³C]- and [U- ¹⁴C]serine into a fetal brachial vein. At tracer serine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, fetal hepatic vein, and fetal femoral vein and from the maternal femoral artery and uterine vein. Analyses were performed for plasma serine and glycine concentration, for serine and glycine ¹³C mole percent enrichment, and for whole blood ¹⁴CO₂ and O₂ concentrations. Uterine and umbilical blood flows were also measured. The placenta had a significant net uptake of fetal serine (2.1 ± 0.5 μmol · min^-1 · kg^-1, P < 0.01). Fetal plasma serine disposal rate (DR) was 42.5 ± 3.9 μmol · min^-1 · kg^-1. CO₂ production from decarboxylation of fetal plasma serine represented 7.9 ± 0.5% of DR, or 10.1 ± 1.2 μmol CO₂ · min^-1 · kg^-1. Fetal plasma glycine enrichment was 59.7 ± 4.9% of fetal plasma serine enrichment. There was a significant loss of tracer serine from the fetal circulation into the placenta accounting for ~45% of infused tracer. Fifteen percent of this was converted to glycine and released into the umbilical circulation. There was a significant uptake of tracer serine by both fetal liver and fetal hindlimb with a significant CO₂ production by both sites with serine oxidation predominantly in the carcass. These results indicate a high fetal serine disposal rate in the lamb, with rapid fetoplacental serine exchange, resulting in a net uptake of fetal serine by the placenta. Significant placental glycine production from fetal plasma serine was demonstrated, supporting the concept of interorgan cycling of serine and glycine between the fetal liver and placenta.