title: Ontogeny of serine hydroxymethyltransferase isoenzymes in fetal sheep liver, kidney, and placenta.
abstract: Serine is an amino acid that is not transported from the placenta to the ovine fetus. Thus, fetal plasma serine levels may be controlled by flux through their relevant biosynthetic pathways. This study was designed to determine, in fetal sheep tissues, the ontogeny of the three key enzymes in the biosynthetic pathway for serine, the cytosolic (c) and mitochondrial (m) isoforms of serine hydroxymethyltransferase (SHMT), phosphoglycerate dehydrogenase (PGD), and phosphoserine aminotransferase (PSAT). PGD and PSAT activity did not vary during gestation in either liver (PSAT, 9.4 +/- 1.3 nmol/min/mg cytosolic protein; and PGD, 76 +/- 10 mU/mg protein) or placenta (PGD, 8.0 +/- 3.6 mU/mg protein). In the liver, cSHMT activity was low early in gestation (0.6 +/- 0.5 nmol/min/mg protein at 45 days), rose in the last one-third of gestation, and peaked in the newborn period (25 +/- 3 nmol/min/mg protein at 1 week of age). Hepatic cSHMT RNA levels parallel the activity pattern. Mitochondrial SHMT was stable throughout gestation and with low constant mSHMT RNA levels. In contrast, the kidney and placenta had high mSHMT and steady low cSHMT activity throughout gestation. These data support the possible role of SHMT in the fetal control of plasma serine levels. While cSHMT may contribute to fetal hepatic serine production, its activity pattern does not support a primary role in the control of fetal hepatic serine biosynthesis. In the placenta, mSHMT may be important for glycine production from serine.
authors.affiliation: Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Narkewicz
authors.forename: R R
authors.initials: RR
authors.lastname: Moores
authors.forename: F C
authors.initials: FC
authors.lastname: Battaglia
authors.forename: F F
authors.initials: FF
authors.lastname: Frerman
mesh_terms: D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism; D005260:Female; D012696:Glycine Hydroxymethyltransferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000201:enzymology*; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D050543:Phosphoglycerate Dehydrogenase; D010920:Placenta / Q000196:embryology / Q000201:enzymology*; D011247:Pregnancy; D012756:Sheep; D000637:Transaminases / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D007527:Isoenzymes; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D012696:Glycine Hydroxymethyltransferase; D000637:Transaminases; C022393:phosphoserine aminotransferase