Relation between transamination of branched-chain amino acids and urea synthesis: evidence from human pregnancy

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N (QN) and carbon (QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 +/- 1.14 vs. pregnant 3.44 +/- 1.11 micromol . kg-1 . min-1; means +/- SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QN was also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 +/- 35 vs. 3rd trimester 135 +/- 16 micromol . kg-1 . h-1; P < 0.05). There was no significant change in QC during pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration (P < 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting (r = 0.59, P = 0.001) and during feeding (r = 0.407, P = 0. 01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as alpha-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.