Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition; Orlando, October 22-24, 1998
THE ONTOGENY OF HEPATIC ENZYME SYSTEMS INVOLVED IN SERINE, GLYCINE AND FOLATE DEPENDENT ONE CARBON METABOLISM IN RABBITS
Serine and glycine have a central role in fetal folate dependent one carbon metabolism. The importance of this metabolic pathway is seen in growth retarded human fetuses who have low plasma levels of serine and glycine compared with normal infants and in the association of neural tube defects with folate deficiency. The goal of this study was to characterize the ontogeny of the key hepatic enzymes involved in folate dependent one carbon metabolism: methylenetetrahydrofolate synthetase (MTHFS) and reductase (MTHFR), cytosolic (cSHMT) and mitochondrial serine hydromethyltransferase (mSHMT), and the glycine cleavage system (GCS) in fetal, postnatal and adult rabbit hepatic tissue. Fresh tissue was fractionated to cytosolic and mitochondrial components in fetal rabbits at midterm (-14 days) n=2 litters, preterm (-9 days) n=4 (2 litters), nearterm (-2 days) n=8 pups, and rabbit pups at 1 day (n=3), 3 days (n=4), 7 days (n=3), 23 days (n=4) of age and adult rabbits (n=9). (Table)
MTHFS increases throughout gestation, peaking in the third week postpartum, before decreasing to adult levels. MTHFR is highest at midgestation, declining to mid-level by late gestation and postnatally, before declining to adult levels. cSHMT is stable throughout gestation, while mSHMT peaks in late gestation. GCS exhibits a preterm and postpartum peak. GCS appears to be the primary source for the production of 5,10-MTHF, a key cofactor in one carbon biosynthesis, early, while MTHFS increases as GCS activity decreases to provide 5,10-MTHF. This suggests coordinated regulation of 5,10-MTHFS and GCS in fetal rabbit liver to maintain 5,10-MTHF production throughout gestation.
PLENARY SESSION III© 1998 Lippincott Williams & Wilkins, Inc.