The DOI matches its Crossref record; 158 of the 159 references it cites were found in a registry or an index.
Vitamin C. Biosynthesis, recycling and degradation in mammals
Open accessAbstract
Vitamin C, a reducing agent and antioxidant, is a cofactor in reactions catalyzed by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases. It is synthesized, in vertebrates having this capacity, from d-glucuronate. The latter is formed through direct hydrolysis of uridine diphosphate (UDP)-glucuronate by enzyme(s) bound to the endoplasmic reticulum membrane, sharing many properties with, and most likely identical to, UDP-glucuronosyltransferases. Non-glucuronidable xenobiotics (aminopyrine, metyrapone, chloretone and others) stimulate the enzymatic hydrolysis of UDP-glucuronate, accounting for their effect to increase vitamin C formation in vivo. Glucuronate is converted to l-gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily. l-Gulonate is converted to l-gulonolactone by a lactonase identified as SMP30 or regucalcin, whose absence in mice leads to vitamin C deficiency. The last step in the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l-ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the endoplasmic reticulum membrane and deficient in man, guinea pig and other species due to mutations in its gene. Another fate of glucuronate is its conversion to d-xylulose in a five-step pathway, the pentose pathway, involving identified oxidoreductases and an unknown decarboxylase. Semidehydroascorbate, a major oxidation product of vitamin C, is reconverted to ascorbate in the cytosol by cytochrome b(5) reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Transmembrane electron transfer systems using ascorbate or NADH as electron donors serve to reduce semidehydroascorbate present in neuroendocrine secretory vesicles and in the extracellular medium. Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH. The degradation of vitamin C in mammals is initiated by the hydrolysis of dehydroascorbate to 2,3-diketo-l-gulonate, which is spontaneously degraded to oxalate, CO(2) and l-erythrulose. This is at variance with bacteria such as Escherichia coli, which have enzymatic degradation pathways for ascorbate and probably also dehydroascorbate.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“So far, the synthesis of vitamin C was documented in all plant species, including algae and photosynthetic protists [1].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [1]
In the citing paper
“They are, therefore, fully dependent on vitamin C intake from the diet [1,2,3].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [1]
In the citing paper
“In contrast to most of the vertebrates, guinea pigs, bats, passeriform birds, and primates, including humans, lack L-gulono-1,4-lactone oxidase, and, hence, cannot synthesize vitamin C.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [1]
In the citing paper
“The pKa of ascorbic acid is 4.1–4.2. Hence, it is present completely as a monoanion—ascorbate at the physiological pH [1,2,4,68].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [1]
In the citing paper
“2,3-diketo-1-gulonic acid can be spontaneously, but also enzymatically, decomposed to erythrulose and oxalate. This reaction is accelerated by bicarbonate [1,3].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [1]
In the citing paper
“There are apparently redundant pathways mediating the reduction of dehydroascorbic acid to ascorbic acid. They include both direct but slow nonenzymatic reduction by glutathione and enzymatic by a couple of enzymes (e.g., glutaredoxin, glutathione transferase omega 2, or thioredoxin reductase). Of note is that the first two enzymes require glutathione for their activity [1,73].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [1]
Citations
Cites
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928
Predicting subcellular localization of proteins based on their N-terminal amino acid sequence.
Emanuelsson, O., Nielsen, H., Brunak, S., & von Heijne, G. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3903 · Cited by 4,419
The Pecking Order of Free Radicals and Antioxidants: Lipid Peroxidation, α-Tocopherol, and Ascorbate
Buettner, G. R. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1074 · Cited by 2,417
Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention
Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J.-H., Chen, S., Corpe, C., Dutta, A., Dutta, S. K., et al. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719272 · Cited by 1,949
Catalytic Metals, Ascorbate and Free Radicals: Combinations to Avoid
Buettner, G. R., & Jurkiewicz, B. A. (1996) · Radiation Research · doi:10.2307/3579271 · Cited by 900
Glutathione-ascorbic acid antioxidant system in animals
Meister, A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36891-6 · Cited by 812
Identification, Characterization, and Crystal Structure of the Omega Class Glutathione Transferases
Philip G. Board, Coggan, M., Chelvanayagam, G., Easteal, S., Jermiin, L. S., Schulte, G. K., Danley, D. E., Hoth, L. R., Griffor, M. C., Kamath, A. V., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001706200 · Cited by 736
The biochemical functions of ascorbic acid
Englard, S., & Seifter, S. (1986) · Annual Review of Nutrition · doi:10.1146/annurev.nu.06.070186.002053 · Cited by 564
Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N., & Yagi, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36884-9 · Cited by 505
Research works printed but not linked: 1
- Moreau R, 1998, Fish acquired ascorbic acid synthesis prior to terrestrial vertebrate emergence, Free Radic Biol Med, 25, 989
Cited by
Sorted by citations
Ascorbic acid: Chemistry, biology and the treatment of cancer
Du, J., Cullen, J. J., & Buettner, G. R. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.06.003 · Cited by 1,106
Cadmium stress: an oxidative challenge
Cuypers, A., Plusquin, M., Remans, T., Jozefczak, M., Keunen, E., Gielen, H., Opdenakker, K., Nair, A. R., Munters, E., Artois, T., et al. (2010) · BioMetals · doi:10.1007/s10534-010-9329-x · Cited by 1,079
Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH
Yun, J., Mullarky, E., Lu, C., Bosch, K. N., Kavalier, A., Rivera, K., Roper, J., Chio, I. I. C., Giannopoulou, E. G., Rago, C., et al. (2015) · Science · doi:10.1126/science.aaa5004 · Cited by 913
Vitamin C: The known and the unknown and Goldilocks
Padayatty, S., & Levine, M. (2016) · Oral Diseases · doi:10.1111/odi.12446 · Cited by 753
Ascorbic acid metabolism and functions: A comparison of plants and mammals
Smirnoff, N. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.03.033 · Cited by 683
Metadata
- Authors
- Linster, C. L., & Van Schaftingen, E.
- Affiliations
- de Duve Institute (BE)
- ORCID
- Linster, Carole L.
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2006-12-06
- Volume
- 274
- Issue
- 1
- Pages
- 1-22
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W2065016714
- Cited by
- 757
- References
- 159
- Citations by year
- 2026: 20 · 2025: 42 · 2024: 66 · 2023: 46 · 2022: 49 · 2021: 61 · 2020: 65 · 2019: 36 · 2018: 26 · 2017: 31 · 2016: 34 · 2015: 31 · 2014: 38 · 2013: 44 · 2012: 37
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- green
- orbilu.uni.lu
- Licence
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- vitamin C, ascorbic acid biosynthesis, UDP-glucuronate, UDP-glucuronosyltransferase, aldehyde reductase, aldo-keto reductase superfamily, L-gulonolactone oxidase, SMP30, regucalcin, dehydroascorbic acid, glutathione, vitamin C degradation, scurvy
- MeSH terms
- Animals, Ascorbic Acid, Carbohydrate Dehydrogenases, Escherichia coli, Glucuronates, Humans, Hydrolysis, Mammals, Models, Biological, Pentose Phosphate Pathway, Uridine Diphosphate Glucuronic Acid, L-Gulonolactone Oxidase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
