RGD Reference Report - Mild neonatal hypoxia exacerbates the effects of vitamin-deficient diet on homocysteine metabolism in rats. - Rat Genome Database

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Mild neonatal hypoxia exacerbates the effects of vitamin-deficient diet on homocysteine metabolism in rats.

Authors: Blaise, S  Alberto, JM  Nedelec, E  Ayav, A  Pourie, G  Bronowicki, JP  Gueant, JL  Daval, JL 
Citation: Blaise S, etal., Pediatr Res 2005 Jun;57(6):777-82. Epub 2005 Apr 21.
RGD ID: 1359026
Pubmed: PMID:15845641   (View Abstract at PubMed)
DOI: DOI:10.1203/01.PDR.0000161406.19231.98   (Journal Full-text)

Elevated plasma homocysteine has been linked to pregnancy complications and developmental diseases. Whereas hyperhomocysteinemia is frequently observed in populations at risk of malnutrition, hypoxia may alter the remethylation of homocysteine in hepatocytes. We aimed to investigate the combined influences of early deficiency in nutritional determinants of hyperhomocysteinemia and of neonatal hypoxia on homocysteine metabolic pathways in developing rats. Dams were fed a standard diet or a diet deficient in vitamins B12, B2, folate, month, and choline from 1 mo before pregnancy until weaning of the offspring. The pups were divided into four treatment groups corresponding to "no hypoxia/standard diet," "hypoxia (100% N2 for 5 min at postnatal d 1)/standard diet," "no hypoxia/deficiency," and "hypoxia/deficiency," and homocysteine metabolism was analyzed in their liver at postnatal d 21. Hypoxia increased plasma homocysteine in deficient pups (21.2 +/- 1.6 versus 13.3 +/- 1.2 microM, p < 0.05). Whereas mRNA levels of cystathionine beta-synthase remained unaltered, deficiency reduced the enzyme activity (48.7 +/- 2.9 versus 83.6 +/- 6.3 nmol/h/mg, p < 0.01), an effect potentiated by hypoxia (29.4 +/- 4.7 nmol/h/mg, p < 0.05). The decrease in methylene-tetrahydrofolate reductase activity measured in deficient pups was attenuated by hypoxia (p < 0.05), and methionine-adenosyltransferase activity was slightly reduced only in the "hypoxia/deficiency" group (p < 0.05). Finally, hypoxia enhanced the deficiency-induced drop of the S-adenosylmethionine/S-adenosylhomocysteine ratio, which is known to influence DNA methylation and gene expression. In conclusion, neonatal hypoxia may increase homocysteinemia mainly by decreasing homocysteine transsulfuration in developing rats under methyl-deficient regimen. It could therefore potentiate the well-known adverse effects of hyperhomocysteinemia.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
methionine biosynthetic process  IDA 1359026; 1359026 RGD 
protein methylation  IDA 1359026; 1359026 RGD 
response to hypoxia  IEP 1359026 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
betaine-homocysteine S-methyltransferase activity  IDA 1359026 RGD 
cobalamin binding  TAS 1359026 RGD 
methyltransferase activity  IDA 1359026; 1359026 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View
Objects Annotated

Genes (Rattus norvegicus)
Bhmt  (betaine-homocysteine S-methyltransferase)
Mthfr  (methylenetetrahydrofolate reductase)
Mtr  (5-methyltetrahydrofolate-homocysteine methyltransferase)

Genes (Homo sapiens)
MTR  (5-methyltetrahydrofolate-homocysteine methyltransferase)


Additional Information