PMID- 12357055
OWN - NLM
STAT- MEDLINE
DCOM- 20030304
LR  - 20131121
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 52
IP  - 4
DP  - 2002 Oct
TI  - Folate cofactors regulate serine metabolism in fetal ovine hepatocytes.
PG  - 589-94
AB  - The fetal liver is the primary site of fetal serine production. The regulation of 
      this unique fetal hepatic serine production is unknown. We hypothesized that 
      serine production would be responsive to folate cofactor supply or hormonal 
      regulation. To test this hypothesis, we determined the effect of key folate 
      cofactors and insulin and glucagon on serine and glycine metabolism in primary 
      culture of fetal ovine hepatocytes. Hepatocytes were cultured in serum-free, 
      low-folate media [5 nM 5-methyl-tetrahydrofolate (THF)] with or without 50 nM 
      5,10-methylene-THF (MTHF) or 5-formyl-THF (FTHF). Serine and glycine production 
      (P) and utilization (U) were determined by stable isotope dilution with 
      [1-(13)C]serine and [1-(13)C]glycine for 24 h. The effect of insulin (1 microM) 
      or glucagon (1 micro M) was determined in a similar manner. Under basal 
      conditions, serine P (43.2 +/- 5.1 micromol/mg DNA per 24 h) is greater than 
      serine U (24.1 +/- 3.1 micromol/mg DNA per 24 h), whereas glycine U (27.3 +/- 3.0 
      micromol/mg DNA per 24 h) exceeds glycine P (16.7 +/- 1.9 micromol/mg DNA per 24 
      h). MTHF results in a significant decrease in serine U (16.0 +/- 2.7 micromol/mg 
      DNA per 24 h; p = 0.02 versus low folate), with no change in serine P. FTHF 
      reduces serine P (36.2 +/- 4.9 micromol/mg DNA per 24 h; p = 0.01), but does not 
      alter serine U. There were no effects on glycine metabolism with 50 nM MTHF or 
      FTHF. Serine P and U were inversely correlated whereas glycine P and U were 
      directly correlated with the media concentration of MTHF or FTHF. Glucagon 
      treatment increased serine U by 260 +/- 65% versus low folate (p = 0.0004) but 
      did not change serine P. Insulin treatment led to parallel increases in both 
      serine P and U. Both folate cofactor availability and hormone concentrations 
      regulate serine metabolism in the fetal liver. We speculate that serine 
      metabolism may be a marker of fetal hepatic folate cofactor supply.
FAU - Narkewicz, Michael R
AU  - Narkewicz MR
AD  - Department of Pediatrics, Section of Pediatric Gastroenterology, University of 
      Colorado School of Medicine and The Children's Hospital, Denver, Colorado 80218, 
      USA. narkewicz.michael@tchden.org
FAU - Jones, Gayle
AU  - Jones G
FAU - Thompson, Henry
AU  - Thompson H
FAU - Kolhouse, Fred
AU  - Kolhouse F
FAU - Fennessey, Paul V
AU  - Fennessey PV
LA  - eng
GR  - 5 T32 DK07038/DK/NIDDK NIH HHS/United States
GR  - DK 48520/DK/NIDDK NIH HHS/United States
GR  - HD 04024/HD/NICHD NIH HHS/United States
GR  - HD 20761/HD/NICHD NIH HHS/United States
GR  - HD 31648/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 452VLY9402 (Serine)
RN  - 935E97BOY8 (Folic Acid)
RN  - G34N38R2N1 (Bromodeoxyuridine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Bromodeoxyuridine
MH  - Folic Acid/*physiology
MH  - Glycine/metabolism
MH  - Hepatocytes/*metabolism
MH  - Serine/*metabolism
MH  - Sheep/*embryology/metabolism
EDAT- 2002/10/03 04:00
MHDA- 2003/03/05 04:00
CRDT- 2002/10/03 04:00
PHST- 2002/10/03 04:00 [pubmed]
PHST- 2003/03/05 04:00 [medline]
PHST- 2002/10/03 04:00 [entrez]
AID - 10.1203/00006450-200210000-00020 [doi]
PST - ppublish
SO  - Pediatr Res. 2002 Oct;52(4):589-94. doi: 10.1203/00006450-200210000-00020.