The role of vitamin B12 in DNA modulation mechanisms
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1
Aristotle University of Thessaloniki, Department of Pharmacology, Greece
The Recommended Dietary Allowances (RDA) of vitamin B12 is 2.4 μg/day, with animal products (meat -especially liver- milk, egg, fish and shellfish) to be the richest dietary sources. Vitamin B12 is important for DNA synthesis and ensures structural stability of important regions of the chromosomes such as the centromeres and the subtelomeric DNA. As a methyl-donor, it participates in the monocarbonic acid metabolic pathway and plays a critical role in DNA methylation, which is especially important during embryogenesis and carcinogenesis. DNA-methylation is catalyzed by DNA methyl-transferases that transfer methyl groups from S-adenosylmethionine (SAM) to cytosine. Vitamin B12 and other methyl donors such as pyridoxal 5'-phosphates (PLP) and folate, are necessary as coenzymes of methyltransferase and lead to the remethylation of homocysteine to methionine. B12 is also responsible for the conversion of methyl-THF to tetrahydrofolate (THF). Both B12 and methyl-THF are required for the methylation of homocysteine to methionine, while methionine is critical for the methylation of various biological molecules, including DNA. Low dietary consumption of B12 results in respectively low serum levels, which induce alterations in DNA synthesis. Thus, deficiency of B12 may lead to DNA damage. Low B12 serum levels were found to have a critical role in neurological diseases, such as the Alzheimer’s, dementia and autism, cardiovascular disease (CAD), and colorectal and breast cancer. Equivocal data were published regarding lung and pancreatic cancer. Moreover, deficiency of B12 appears to affect pregnancy, especially by causing NTDs (Neural Tube Defects) to the infant. Dietary B12 can affect epigenetic mechanisms by regulating DNA methylation status. Therefore, it might help in protecting against chronic diseases and cancer and serve as the basis for new treatments regimens.
Keywords:
B12,
vitamin,
Nutrigenomics,
DNA Methylation,
Cancer,
Diet
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Poster
Topic:
Nutrigenomics
Citation:
Karapiperi
K,
Gousis
C and
Papaioannidou
P
(2010). The role of vitamin B12 in DNA modulation mechanisms.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00140
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Received:
28 Oct 2010;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Paraskevi Papaioannidou, Aristotle University of Thessaloniki, Department of Pharmacology, Thessaloniki, Greece, ppap@auth.gr