PMID- 20650144
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121002
LR  - 20190917
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 9
IP  - 5
DP  - 1995 Oct
TI  - Investigation, using rat embryo culture, of the role of methionine supply in 
      folic acid-mediated prevention of neural tube defects.
PG  - 677-84
AB  - Peri-conceptional folic acid supplementation has become a well established way to 
      prevent neural tube defects (NTDs) and such supplementation reduces the 
      prevalence of these defects by approximately 70%. However, the mechanism of the 
      preventive effect of folic acid is not clear. This overview focuses on the 
      biochemical basis of folic acid-preventable NTDs and on the results obtained with 
      whole embryo culture that may help to shed some light on the mechanisms that 
      underlie the preventive effect of folic acid. Culturing gestational day (GD) 9.5 
      rat embryos on diet-induced folate-deficient rat serum resulted in many 
      malformations, but no NTDs and this embryotoxicity could only partly be overcome 
      by supplementation with N(5)-methyltetrahydrofolate(5-methylTHF). This indicates 
      that there may be an indirect effect of folate deficiency. Besides an important 
      role in purine and thymidine synthesis, folate drives the methylation cycle in 
      which the methyl group of 5-methylTHF is transferred to numerous biomolecules. In 
      this process homocysteine and methionine are constantly interconverted. It was 
      hypothesized that folate deficiency might lead to a toxic accumulation of 
      homocysteine. However, only homocysteine levels 100-fold higher than 
      physiological levels were embryotoxic to cultured GD10 rat embryos. Moreover, 1 
      and 2 mm l-homocysteine could prevent NTDs in GD9.5 rat embryos when they were 
      cultured in human serum. Addition of 100 mum methionine had the same preventive 
      effect, but addition of 1 mm folinic acid could not prevent the NTDs. When 
      embryos were cultured in cow or canine serum, methionine had a similar preventive 
      effect. These results suggest folic acid mediated prevention of NTDs may be based 
      on an increase of the methionine supply and possibly its supportive action 
      towards the methylation cycle.
FAU - Vanaerts, L A
AU  - Vanaerts LA
AD  - Department of Toxicology, University of Nijmegen, PO Box 9101, 6500 HB 
      NijmegenThe Netherlands.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 2010/07/24 06:00
PHST- 2010/07/24 06:00 [entrez]
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
AID - 0887-2333(95)00070-O [pii]
AID - 10.1016/0887-2333(95)00070-o [doi]
PST - ppublish
SO  - Toxicol In Vitro. 1995 Oct;9(5):677-84. doi: 10.1016/0887-2333(95)00070-o.