Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon metabolism in rabbits

Serine occupies a central position in folate-dependent, one-carbon metaboli sm through 5,10-methylenetetrahydrofolate (MTHF) and 5-formyltetrahydrofola te (FTHF). We characterized the ontogeny of the specific activity of key en zymes involved in serine, 5,10-MTHF, and 5-FTHF metabolism: methenyltetrahy drofolate synthetase (MTHFS), MTHF reductase (MTHFR), the glycine cleavage system (GCS), methionine synthase (MS), and serine hydroxymethyltransferase (SHMT) in rabbit liver, placenta, brain, and kidney. In liver, MTHFS activ ity is low in the fetus (0.36 +/- 0.07 nmol.min(-1).mg protein(-1)), peaks at 3 wk (1.48 +/- 0.50 nmol.min(-1).mg protein 21), and then decreases to a dult levels (1.13 +/- 0.32 nmol.min(-1).mg protein 21). MTHFR activity is h ighest early in gestation (24.9 +/- 2.4 nmol.h(-1).mg protein 21) and decli nes rapidly by birth (4.7 +/- 1.3 nmol.h(-1).mg protein 21). MS is highest during fetal life and declines after birth. Cytosolic SHMT activity does no t vary during development, but mitochondrial SHMT peaks at 23 days. GCS act ivity is high in the fetus and the neonate, declining after weaning. In pla centa and brain, all activities are low throughout gestation. Cytosolic and mitochondrial SHMT activities are low in kidney and rise after weaning, wh ereas MTHFS is low throughout development. These data suggest that the live r is the primary site of activity for these enzymes. Throughout development , there are multiple potential sources for production of 5,10-MTHF, but ear ly in gestation high MTHFR activity and low MTHFS activity could reduce 5,1 0-MTHF availability.