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.
Kalhan
S C
SC
Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA.
Rossi
K Q
KQ
Gruca
L L
LL
Super
D M
DM
Savin
S M
SM
D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D002151:Calorimetry; D002245:Carbon Dioxide / Q000032:analysis; D002247:Carbon Isotopes; D005260:Female; D006801:Humans; D007930:Leucine / Q000378:metabolism; D013058:Mass Spectrometry; D009587:Nitrogen Isotopes; D010100:Oxygen / Q000032:analysis; D010101:Oxygen Consumption; D011247:Pregnancy / Q000502:physiology*; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D012016:Reference Values; D014508:Urea / Q000378:metabolism*
D000597:Amino Acids, Branched-Chain; D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D002245:Carbon Dioxide; D014508:Urea; D007930:Leucine; D010100:Oxygen