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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-8-28
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pubmed:abstractText |
The disposition of whole blood mono-to hexaglutamyl methylfolate and plasma homocysteine (HCY) was used to evaluate potential lesion sites in one-carbon metabolism which could be responsible for neural tube defect(NTD)-affected pregnancies. An isocratic high-performance liquid chromatographic system (HPLC) with photodiode array detection was used to quantify and speciate whole-blood methylfolate into mono-, di-, tri-, tetra-, penta-, and hexaglutamate forms. This technique was also used with off-line radioassay to identify nonmethyl whole-blood folates. Isocratic HPLC with fluorescence detection was used to quantify SBDF derivatized homocysteine in plasma. The study investigated blood from 11 women who had experienced a previous NTD-affected pregnancy and 11 controls of similar age and social class. No subjects were pregnant. HCY levels were significantly higher in NTD subjects (P = 0.0486, 95% CI-2.799,0.001 using the Mann-Whitney test), as was the ratio of known intracellular (tri-to hexaglutamyl) methylfolate compared to extracellular (mono- and diglutamyl) methylfolate (P = 0.0062 95% CI-0.543, 3.862 using the Mann-Whitney test). Vitamin B12, red cell folate, circulating total methylfolate, and circulating mono-to hexaglutamyl methylfolates showed no difference between population groups. The disposition between individual and cumulative glutamate chain lengths of methylfolate showed significant trends which differed between population groups: (i) total blood methylfolate (Glu1-6) appears to be utilized by N-5-methyltetrahydrofolate:homocysteine methyltransferase (MS) in control blood but not NTD blood, where it appears to accumulate following a 45-min incubation; (ii) whole-blood hexaglutamyl methylfolate (5CH3-H4PteGlus) becomes a larger proportion of the total blood methylfolate in NTD than in control populations; and (iii) the intermediate glutamate chains of methylfolate (Glu1-5) remain relatively constant as 5CH3-H4PteGlu6 accumulates in NTD but appear to increase linearly with 5CH3-H4PteGlu6 in controls. The significant elevation of HCY in the NTD population is associated with the increasing proportion of 5CH3-H4PteGlu6 relative to the total methylfolate, since, when corrected for HCY level, the proportion of 5CH3-H4PteGlus to total methylfolate is similar in NTD and control populations. These trends are consistent with a defect at the level of vitamin B12 dependent MS which "traps" folate at the 5CH3-H4PteGlus level.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1077-3150
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28-40
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9232194-5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase,
pubmed-meshheading:9232194-Erythrocytes,
pubmed-meshheading:9232194-Female,
pubmed-meshheading:9232194-Folic Acid,
pubmed-meshheading:9232194-Glutamic Acid,
pubmed-meshheading:9232194-Humans,
pubmed-meshheading:9232194-Maternal-Fetal Exchange,
pubmed-meshheading:9232194-Neural Tube Defects,
pubmed-meshheading:9232194-Pregnancy,
pubmed-meshheading:9232194-Pregnancy Complications,
pubmed-meshheading:9232194-Risk Factors
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pubmed:year |
1997
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pubmed:articleTitle |
Risk of neural tube defect-affected pregnancy is associated with a block in maternal one-carbon metabolism at the level of N-5-methyltetrahydrofolate:homocysteine methyltransferase.
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pubmed:affiliation |
University of Leeds Research School of Medicine, Centre for Reproduction, Growth and Development, Leeds General Infirmary, West Yorkshire, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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