Abstract
A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data converge towards a crucial role played by many micronutrients in genome integrity maintenance and in the establishment of a correct DNA methylation pattern. Failure in the proper accomplishment of these processes accelerates senescence and increases the risk of developing cancer, by promoting the formation of chromosome aberrations and deregulating the expression of oncogenes. Here, the main recent evidence regarding the impact of some B vitamins on DNA damage and cancer is summarized, providing an integrated and updated analysis, mainly centred on vitamin B6. In many cases, it is difficult to finely predict the optimal vitamin rate that is able to protect against DNA damage, as this can be influenced by a given individual's genotype. For this purpose, a precious resort is represented by model organisms which allow limitations imposed by more complex systems to be overcome. In this review, we show that Drosophila can be a useful model to deeply understand mechanisms underlying the relationship between vitamin B6 and genome integrity.
Highlights
Vitamins B9, B12, B1 and B6 are the source of coenzymes that participate in one carbon metabolism, in which 1C units are royalsocietypublishing.org/journal/rsob Open Biol. 10: 200034
400 mcg day−1 of dietary folate equivalentsa for adults; recommendation is that women of childbearing age consume an additional 400 mcg day−1 of folic acid from supplements vitamin B12 only present in animal products because it is a product of bacteria synthesis: meat, poultry, fish, seafood, eggs, or fortified foods to decrease the risk of neural tube defects 2.4 mcg day−1 for adults; it is recommended for older adults to meet their RDA with fortified foods or supplements because milk and milk products; not found in plant foods; many many are unable to absorb naturally occurring vitamin B12 foods are fortified with synthetic vitamin B12
The relationship between vitamin B6 and cancer, deduced from studies reported in this review, is complex and leads us to speculate that it can result from a balance between its antioxidant properties on the one hand and its role as a micronutrient important for cell metabolism on the other hand
Summary
Vitamin B6 is an ensemble of six substituted pyridine compounds or vitamers: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their related 50-phosphate derivatives (figure 2). The different B6 vitamers are interconverted through a salvage pathway that involves pyridoxal kinase (PDXK), pyridoxine 5’-phosphate oxidase (PNPO) and several phosphatases (figure 2). An intracellular, cytosolic PLP phosphatase exists, which is ubiquitously expressed in humans and is involved in vitamin B6 catabolism [55]. Another important component of vitamin B6 metabolism is the recently discovered PLP-binding protein (PLP-BP), widespread in all kingdoms of life, with no catalytic activity but with an important regulatory function in PLP homeostasis [56]. PM, PN and PL are absorbed from the upper small intestine by a carrier-mediated system and delivered through the portal circulation to the liver In this organ, they are converted to PLP through the combined action of PDXK and PNPO. Catabolism of vitamin B6 consists in the oxidation of PL to 4-pyridoxic acid by aldehyde oxidase 1 (AOX-1) and NAD-dependent dehydrogenases [60]
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