Gamma-carboxyglutamic acid excretion into rat amniotic fluid during late gestation.
The amino acid gamma-carboxyglutamate is the product of post-translational vitamin K-dependent carboxylation of peptide bound glutamic acid residues. Activity of the microsomal vitamin K-dependent carboxylase which catalyzes gamma-carboxyglutamate formation has been studied in numerous tissues, including liver and lung. Catabolism of gamma-carboxyglutamate containing proteins leads to gamma-carboxyglutamate excretion into the urine, thus quantitation of urinary gamma-carboxyglutamate can be used to assess vitamin K status, as well as the turnover of gamma-carboxyglutamate containing proteins. Since fetal urine is a major component of amniotic fluid, samples were obtained during late gestation in the rat (days 18-20) and analyzed for gamma-carboxyglutamate by reversed phase liquid chromatography to better define gestational changes in fetal vitamin K-dependent carboxylation. Relative to gestational age 18 days, amniotic fluid gamma-carboxyglutamate concentrations increased by 25% at 19 days (P less than 0.02) and by 105% at 20 days (P less than 0.001). When expressed per unit creatinine to correct for change in body mass and/or amniotic fluid volume, these differences are 15% (NS) at 19 days and 70% (P less than 0.02) at 20 days. These increases are prevented by maternal treatment with sodium warfarin. Amniotic fluid gamma-carboxyglutamate concentrations are 7-12 times greater than those in adult rat urine. During the same developmental interval (18-20 days), both lung and liver carboxylase activities increase by more than two-fold. These studies suggest that gestational age associated increases in carboxylase activity measured in vitro are associated with increased turnover of gamma-carboxyglutamate containing proteins in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Gallaher
K J
KJ
Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Wolpert
E B
EB
Rannels
S R
SR
D015055:1-Carboxyglutamic Acid / Q000378:metabolism*; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003404:Creatinine / Q000032:analysis; D005260:Female; D005865:Gestational Age; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014859:Warfarin / Q000494:pharmacology
D015055:1-Carboxyglutamic Acid; D014859:Warfarin; D003404:Creatinine