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Am J Physiol Endocrinol Metab 275: E423-E431, 1998;
0193-1849/98 $5.00
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Vol. 275, Issue 3, E423-E431, September 1998

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

Satish C. Kalhan, Karen Q. Rossi, Lourdes L. Gruca, Dennis M. Super, and Samuel M. Savin

Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106

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 µmol · 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 µmol · 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.

leucine; stable isotopes; nitrogen accretion


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