The biochemical functions of ascorbic acid

Englard, S; Seifter, S

doi:10.1146/annurev.nu.06.070186.002053

Cited by 564Vitamin C and Antioxidants ResearchMicrobial metabolism and enzyme functionAntioxidant Activity and Oxidative Stress

The biochemical functions of ascorbic acid

Englard, S, Seifter, S·1986·Annual Review of Nutrition

DOI 10.1146/annurev.nu.06.070186.002053

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Abstract

SCOPE OF THIS REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 BIOSYNTHESIS AND REQUIREMENTS OF ASCORBIC ACID . . . . . . . . . . . . . . . . . . . . . . . . . 366 METABOLISM OF ASCORBATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367 ACTIONS AND FUNCTIONS OF ASCORBATE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 DOPAMINE !3-HYDROXYLASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . 372 PEPTIDYL GLYCINE a-AMIDATING MONOOXYGENASE... . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 4-HYDROXYPHENYLPYRUV ATE DIOXYGENASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374 PROL YL AND L YSYL HYDROXYLASES FOR COLLAGENS . . . . . . . . . . . . . . . . . . . . . . . . . . . 376 HYDROXYLATION OF OTHER PROTEINS . . . .. . . ...... . . . . 383 Elastin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 C1q o/ Complement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384 DIOXYGENASE REACTIONS OF PYRIMIDINES AND NUCLEOSIDES . . . . . . . . . . . . . . 385 CARNITINE PATHWAY HYDROXYLASES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386 OTHER POSSIBLE FUNCTIONS OF ASCORBATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 CONCLUDING REMARKS ... . . ........ . . . . . .. . .. . .. . . ...... .... . . ........ .... ..... . . . . 391

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Recommendations for vitamin C intake differ substantially from 40 to 120 mg/day in various countries.
“Recommendations differ substantially from 40 to 120 mg/day in various countries.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
In pregnant women, an additional 5-10 mg of vitamin C is recommended, and 25 mg in lactating mothers.
“In pregnant women, an additional 5–10 mg is recommended (25 mg in lactating mothers) [3,4,5,6].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
Physiologically high vitamin C levels (2-10 mM) are found in neurons and endocrine cells, particularly the adrenal and pituitary gland, apparently related to the synthesis of hormones and neuro-mediators.
“Physiologically high levels (2–10 mM) are found in neurons and endocrine cells (particularly, the adrenal and pituitary gland), which is apparently related to the synthesis of hormones and neuro-mediators described below [4,6,8,72,73].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
The pKa of ascorbic acid is 4.1-4.2, so it is present completely as a monoanion-ascorbate-at physiological pH.
“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 [4]
Ascorbic acid is involved in the reduction of copper in dopamine-β-hydroxylase.
“Ascorbic acid seems to be involved in the reduction of copper.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]

The α-amidation reaction catalyzed by PAM is crucial for the production of a number of hormones/neurotransmitters (e.g., calcitonin, oxytocin, vasopressin, GLP-1, substance P, neuropeptide Y).
“The reaction is crucial for the production of a number of hormones/neurotransmitters (e.g., calcitonin, oxytocin, vasopressin, GLP-1, substance P, neuropeptide Y)”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
4-hydroxyphenylpyruvate dioxygenase catalyzes decarboxylation, substituent migration, and aromatic oxygenation in a single catalytic cycle, converting 4-hydroxyphenylpyruvate to homogentisate as part of the tyrosine elimination pathway.
“It catalyzes an uncommon reaction in humans, which involves decarboxylation, substituent migration, and aromatic oxygenation in a single catalytic cycle. The 4-hydroxyphenylpyruvate is converted to homogentisate (2,5-dihydroxyphenylacetate, Figure 6) as a part of the tyrosine elimination pathway.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
Ascorbate likely enables conversion between a cupric and cuprous state and is reduced stoichiometrically to an ascorbyl radical in PAM.
“Ascorbate likely enables conversion between a cupric and cuprous state and is reduced stoichiometrically to an ascorbyl radical.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
The superiority of vitamin C over other reducing agents was shown for 4-hydroxyphenylpyruvate dioxygenase.
“Furthermore, here, the superiority of vitamin C over other reducing agents was shown [4,144].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
The hydroxylation active site of PAM is composed of two copper ions and the corresponding reaction is ascorbate-dependent.
“The former active site is composed of two copper ions and the corresponding reaction is ascorbate-dependent.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
Other reductants can replace ascorbic acid in PAM but are less potent.
“Other reductants can replace ascorbic acid but are less potent [4,72,147,148,149].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]
The first symptoms of vitamin C deficiency such as lassitude and tiredness, occurring at plasma levels approximately below 20 μM, can be due to decreased synthesis of carnitine.
“The first mentioned symptoms of vitamin C deficiency such as lassitude and tiredness, occurring at plasma levels approximately below 20 µM, can be due to decreased synthesis of carnitine since a deficiency in carnitine leads to decreased oxidation of fatty acids in muscles and other tissues.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [4]

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Authors: Englard, S., & Seifter, S.
Venue: Annual Review of Nutrition
Publisher: Annual Reviews
Published: 1986-07
Volume: 6
Issue: 1
Pages: 365-406
ISSN: 0199-9885 (ISSN-L)
1545-4312
DOI: 10.1146/annurev.nu.06.070186.002053
OpenAlex: W2180583964
Cited by: 564
References: 89
Citations by year: 2026: 9 · 2025: 16 · 2024: 20 · 2023: 25 · 2022: 31 · 2021: 17 · 2020: 30 · 2019: 13 · 2018: 22 · 2017: 20 · 2016: 20 · 2015: 22 · 2014: 20 · 2013: 22 · 2012: 20
FWCI: 7.62
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Nutrition (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01am021197-08)
National Institute on Aging (2P01 AG 00374)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords: vitamin C, ascorbic acid metabolism, ascorbic acid biosynthesis, dopamine beta-hydroxylase, peptidylglycine alpha-amidating monooxygenase, prolyl hydroxylase, lysyl hydroxylase, collagen hydroxylation, protein hydroxylation, ascorbate deficiency
MeSH terms: Oxidoreductases Acting on CH-NH Group Donors, Animals, Ascorbic Acid, Ascorbic Acid Deficiency, Carnitine, Cell Line, Chemistry, Collagen, Complement Activating Enzymes, Dopamine beta-Hydroxylase, Elastin, Fibroblasts, Free Radicals, Humans, Mixed Function Oxygenases, Hydroxylation, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase, Multienzyme Complexes, Nucleosides, Nutritional Requirements, Oxidation-Reduction, Procollagen-Proline Dioxygenase, Pyrimidines, 4-Hydroxyphenylpyruvate Dioxygenase, Complement C1q, Chemical Phenomena

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The biochemical functions of ascorbic acid

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