Evaluation of phenylalanine and tyrosine metabolism in late human pregnancy

Abstract

The [ 2H 5]-phenylalanine method for measurement of protein metabolism requires the phenylalanine hydroxylation to tyrosine to be calculated from the tyrosine flux. Although this can be estimated, for pregnancy, we made a direct measurement of the molar ratio of the fluxes of tyrosine and phenylalanine from protein breakdown ( Pt Pp ) using [ 2H 2]-tyrosine infusion. Six normal pregnant women were studied at 37 weeks' gestation. While fasting, they were administered a 3-hour primed-constant infusion with [ 13C]-leucine, [ 2H 5]-phenylalanine, and [ 2H 2]-tyrosine. Leucine (α-ketoisocaproic acid [KIC]) flux was 136.2 ± 15.1 μmol/kg/h (mean ± SD], phenylalanine flux 41.2 ± 5.6, and tyrosine flux 25.0 ± 6.0, and phenylalanine hydroxylation was 3.3 ± 2.1 μmol/kg/h. The mean tyrosine to phenylalanine molar flux ratio ( Pt Pp ) was 0.52 ± 0.10, lower than the ratio of 0.65 to 0.85 reported in normal nonpregnant subjects and 0.73 estimated from animal studies. We studied protein metabolism in six additional pregnant women and six nonpregnant women using [ 13C]-leucine and [ 2H 5]-phenylalanine infusions only and applied the lower Pt Pp ratio to the former group. Tyrosine flux (42.0 ± 7.2 μmol/kg/h) and phenylalanine hydroxylation (9.2 ± 4.2 μmol/kg/h) were significantly higher in nonpregnant subjects than in both groups of pregnant subjects. The percent contribution of phenylalanine hydroxylation to total tyrosine flux was reduced from 20% to 14%. When using [ 2H 5]-phenylalanine to study whole-body protein metabolism in pregnancy and tyrosine flux is not measured directly by infusion of [ 2H 2]-tyrosine, the lower Pt Pp ratio is required. The phenylalanine model shows that tyrosine flux derived from protein breakdown and phenylalanine hydroxylation are both reduced in pregnancy.