PMID- 6355408
OWN - NLM
STAT- MEDLINE
DCOM- 19831217
LR  - 20180330
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 113
IP  - 11
DP  - 1983 Nov
TI  - The effect of chronic phenytoin treatment on tissue folate concentrations and on 
      the activities of the methyl synthetic enzymes in the rat.
PG  - 2368-74
AB  - The folacin-depleting effect of phenytoin has been known clinically for many 
      years, but a systematic investigation of this effect in animals has never been 
      undertaken. In this study we found that chronic oral phenytoin treatment (100 
      mg/kg every 12 hours for 8 weeks) in rats significantly affected concentrations 
      of folates in both liver and brain. Concentration of liver folates dropped to 
      one-third the normal level even though concentration of plasma folates was not 
      affected. Concentration of brain folates increased over the first 2 weeks of 
      treatment and then declined to a level approximately three-fourths the normal 
      concentration. The apparent activity of 5,10-methylenetetrahydrofolate reductase 
      (MTR) increased as a function of the length of treatment in both brain and liver, 
      but when phenytoin was added to the MTR assay in vitro, the activity was 
      inhibited. No significant effects of phenytoin on the activities of serine 
      hydroxymethyltransferase (SHMT), 5-methyltetrahydrofolate:homocysteine 
      methyltransferase (MHMT) or methionine adenosyltransferase (MAT) were observed 
      either in vivo or in vitro. These data are consistent with the hypothesis that 
      phenytoin interacts with the metabolism of folates at the enzymatic level.
FAU - Carl, G F
AU  - Carl GF
FAU - Smith, D B
AU  - Smith DB
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 6158TKW0C5 (Phenytoin)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.5.1.20 (5,10-Methylenetetrahydrofolate Reductase (FADH2))
RN  - EC 2.- (Transferases)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.13 (5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase)
RN  - EC 2.1.2.1 (Glycine Hydroxymethyltransferase)
RN  - EC 2.5.1.6 (Methionine Adenosyltransferase)
SB  - IM
MH  - 5,10-Methylenetetrahydrofolate Reductase (FADH2)
MH  - 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/*metabolism
MH  - Alcohol Oxidoreductases/*metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Folic Acid/*metabolism
MH  - Glycine Hydroxymethyltransferase/*metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Methionine Adenosyltransferase/*metabolism
MH  - Methyltransferases/*metabolism
MH  - Phenytoin/*pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Time Factors
MH  - Transferases/*metabolism
EDAT- 1983/11/01 00:00
MHDA- 1983/11/01 00:01
CRDT- 1983/11/01 00:00
PHST- 1983/11/01 00:00 [pubmed]
PHST- 1983/11/01 00:01 [medline]
PHST- 1983/11/01 00:00 [entrez]
AID - 10.1093/jn/113.11.2368 [doi]
PST - ppublish
SO  - J Nutr. 1983 Nov;113(11):2368-74. doi: 10.1093/jn/113.11.2368.