Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 122, Issue -, Pages 116-129Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2018.03.033
Keywords
Ascorbic acid; Vitamin C; Hydrogen peroxide; Ascorbate peroxidase; Ascorbate oxidase; Gulonolactone oxidase; Galactonolactone dehydrogenase; Dehydroascorbate; Monodehydroascorbate; Dioxygenase; Iron reduction; Epigenetics; vtc mutants
Funding
- UK Biotechnology and Biological Sciences Research Council [BB/I020004/1, BB/N001311/1]
- BBSRC [BB/I020004/1, BB/N001311/1, BB/G021678/1] Funding Source: UKRI
Ask authors/readers for more resources
Ascorbic acid is synthesised by eukaryotes, the known exceptions being primates and some other animal groups which have lost functional gulonolactone oxidase. Prokaryotes do not synthesise ascorbate and do not need an ascorbate supply, so the functions that are essential for mammals and plants are not required or are substituted by other compounds. The ability of ascorbate to donate electrons enables it to act as a free radical scavenger and to reduce higher oxidation states of iron to Fe2+. These reactions are the basis of its biological activity along with the relative stability of the resulting resonance stabilised monodehydroascorbate radical. The importance of these properties is emphasised by the evolution of at least three biosynthetic pathways and production of an ascorbate analogue, erythroascorbate, by fungi. The iron reducing activity of ascorbate maintains the reactive centre Fe2+ of 2-oxoglutarate-dependent dioxygenases (2-ODDs) thus preventing inactivation. These enzymes have diverse functions and, recently, the possibility that ascorbate status in mammals could influence 2-ODDs involved in histone and DNA demethylation thereby influencing stem cell differentiation and cancer has been uncovered. Ascorbate is involved in iron uptake and transport in plants and animals. While the above biochemical functions are shared between mammals and plants, ascorbate peroxidase (APX) is an enzyme family limited to plants and photosynthetic protists. It provides these organisms with increased capacity to remove H2O2 produced by photosynthetic electron transport and photorespiration. The Fe reducing activity of ascorbate enables hydroxyl radical production (pro-oxidant effect) and the reactivity of dehydroascorbate (DHA) and reaction of its degradation products with proteins (dehydroascorbylation and glycation) is potentially damaging. Ascorbate status influences gene expression in plants and mammals but at present there is little evidence that it acts as a specific signalling molecule. It most likely acts indirectly by influencing the redox state of thiols and 2ODD activity. However, the possibility that dehydroascorbylation is a regulatory post-translational protein modification could be explored.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available