HOW IMPORTANT OF VITAMIN B12 & FOLATE

[zack lim]

Findings
Vitamin B12 and folate participate in a number of biochemical reactions that affect methyl group production and transfer. Vitamin B12 is a cofactor for methionine synthase (MS) that catalyses the conversion of homocysteine to methionine. Methionine is then converted to S-adenosylmethionine (SAM), a universal methyl group donor for methylation of DNA and RNA. The transfer of a methyl group to the 5-carbon cytosine residue by SAM is catalysed by DNA methyltransferase enzymes ,
DNA methylation is a fundamental mechanism for the epigenetic control of gene expression and the maintenance of genomic integrity , DNA hypermethylation can lead to transcriptional silencing by blocking transcription factors and DNA hypomethylation to genomic instability and the expression of genes that would be otherwise suppressed . DNA methylation plays a critical role in the generation of oncogenic point mutations, silencing of tumor suppressor genes and in the activation of the cancer process .
Low vitamin B12 status results in reduced MS activity, impaired remethylation of homocysteine to methionine and subsequent SAM production. Consequently, methylation reactions are impaired and DNA methylation capacity is reduced. Severe vitamin B12 deficiency leads to neurological manifestations such as myelopathy, neuropathy, dementia and neuropsychiatric abnormalities and to demyelination in the central nervous system . DNA hypomethylation could be a link between vitamin B12 deficiency and neurological pathology. Although the association was not maintained in multivariate analysis, preliminary analysis showed that low tissue B12 concentrations were associated with DNA hypomethylation in human squamous cell lung cancer , B12 deficient diet has decreased DNA methylation and increased uracil incorporation in rats , DNA hypomethylation has been reported in fetal brains with neural tube defects . The transcobalamin receptor (TCblR)/CD320 knock out (KO) mouse provides a model to investigate the relationship between severe B12 deficiency and DNA methylation status.

Sent from my iPhone