Ascorbate Is a Primary Antioxidant in Mammals

Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radica...

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Main Authors: Junichi Fujii, Tsukasa Osaki, Tomoki Bo
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/19/6187
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author Junichi Fujii
Tsukasa Osaki
Tomoki Bo
author_facet Junichi Fujii
Tsukasa Osaki
Tomoki Bo
author_sort Junichi Fujii
collection DOAJ
description Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms.
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spelling doaj.art-f9df924a1af24a09a6c39298484b45282023-11-23T21:07:08ZengMDPI AGMolecules1420-30492022-09-012719618710.3390/molecules27196187Ascorbate Is a Primary Antioxidant in MammalsJunichi Fujii0Tsukasa Osaki1Tomoki Bo2Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, JapanDepartment of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, JapanLaboratory Animal Center, Institute for Promotion of Medical Science Research, Yamagata University Faculty of Medicine, Yamagata 990-9585, JapanAscorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms.https://www.mdpi.com/1420-3049/27/19/6187ascorbateGULORGNAKR1Aantioxidantradical scavenging
spellingShingle Junichi Fujii
Tsukasa Osaki
Tomoki Bo
Ascorbate Is a Primary Antioxidant in Mammals
Molecules
ascorbate
GULO
RGN
AKR1A
antioxidant
radical scavenging
title Ascorbate Is a Primary Antioxidant in Mammals
title_full Ascorbate Is a Primary Antioxidant in Mammals
title_fullStr Ascorbate Is a Primary Antioxidant in Mammals
title_full_unstemmed Ascorbate Is a Primary Antioxidant in Mammals
title_short Ascorbate Is a Primary Antioxidant in Mammals
title_sort ascorbate is a primary antioxidant in mammals
topic ascorbate
GULO
RGN
AKR1A
antioxidant
radical scavenging
url https://www.mdpi.com/1420-3049/27/19/6187
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