The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid
Open accessAbstract
In order to survive in an oxygen environment, aerobic organisms have developed numerous mechanisms to protect against oxygen radicals and singlet oxygen. One such mechanism, which appears to have attained particular significance during primate evolution, is the direct scavenging of oxygen radicals, singlet oxygen, oxo-haem oxidants and hydroperoxyl radicals by uric acid. In the present paper we demonstrate that another important ‘antioxidant’ property of uric acid is the ability to form stable co-ordination complexes with iron ions. Formation of urate-Fe3+ complexes dramatically inhibits Fe3+-catalysed ascorbate oxidation, as well as lipid peroxidation in liposomes and rat liver microsomal fraction. In contrast with antioxidant scavenger reactions, the inhibition of ascorbate oxidation and lipid peroxidation provided by urate's ability to bind iron ions does not involve urate oxidation. Association constants (Ka) for urate-iron ion complexes were determined by fluorescence-quenching techniques. The Ka for a 1:1 urate-Fe3+ complex was found to be 2.4 × 10(5), whereas the Ka for a 1:1 urate-Fe2+ complex was determined to be 1.9 × 10(4). Our experiments also revealed that urate can form a 2:1 complex with Fe3+ with an association constant for the second urate molecule (K'a) of approx. 4.5 × 10(5). From these data we estimate an overall stability constant (Ks approximately equal to Ka × K'a) for urate-Fe3+ complexes of approx. 1.1 × 10(11). Polarographic measurements revealed that (upon binding) urate decreases the reduction potential for the Fe2+/Fe3+ half-reaction from −0.77 V to −0.67 V. Thus urate slightly diminishes the oxidizing potential of Fe3+. The present results provide a mechanistic explanation for our previous report that urate protects ascorbate from oxidation in human blood. The almost saturating concentration of urate normally found in human plasma (up to 0.6 mM) represents 5-10 times the plasma ascorbate concentration, and is orders of magnitude higher than the ‘free’ iron ion concentration. These considerations point to the physiological significance of our findings.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“There is considerable evidence that this too is a disease of iron overload, and that uric acid accumulation – as both an antioxidant and an iron chelator [1348] – is in response to the iron overload [1349,1350] and with highly beneficial remission of gouty symptoms occurring on depletion of iron by phlebotomy [1351].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1348]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
[30] Microsomal lipid peroxidation
Buege, J. A., & Aust, S. D. (1978) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(78)52032-6 · Cited by 13,564
Ames, B. N., Cathcart, R., Schwiers, E., & Hochstein, P. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6858 · Cited by 2,915
Self-citationElectrochemistry at Solid Electrodes
Adams, R. N. (1969) · Medical Entomology and Zoology · Cited by 1,296
Role of metals in oxygen radical reactions
Aust, S. D., Morehouse, L. A., & Thomas, C. E. (1985) · Journal of Free Radicals in Biology & Medicine · doi:10.1016/0748-5514(85)90025-x · Cited by 1,150
Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide.
Kellogg, E. W., & Fridovich, I. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39909-x · Cited by 509
Ascorbic Acid: Chemistry, Metabolism, and Uses
(1982) · Advances in Chemistry · doi:10.1021/ba-1982-0200 · Cited by 458
Fluorescence of riboflavin and flavin-adenine dinucleotide
Weber, G. (1950) · Biochemical Journal · doi:10.1042/bj0470114 · Cited by 404
Albert, A. (1953) · Biochemical Journal · doi:10.1042/bj0540646 · Cited by 275
Chapter 4 Lipid Vesicles as Carriers for Introducing Biologically Active Materials into Cells
Poste, G. H., Papahadjopoulos, D., & Vail, W. J. (1976) · Methods in cell biology · doi:10.1016/s0091-679x(08)60468-9 · Cited by 131
Conservation of vitamin C by uric acid in blood
Sevanian, A., Davies, K. J. A., & Hochstein, P. E. (1985) · Journal of Free Radicals in Biology & Medicine · doi:10.1016/0748-5514(85)90015-7 · Cited by 125
Self-citationOn the Mechanism of Peroxidation of Uric Acids by Hemoproteins
Howell, R. R., & Wyngaarden, J. Β. (1960) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64505-3 · Cited by 121
The dye-sensitized photooxidation of purine and pyrimidine derivatives
Simon, M. I., & Vunakis, H. V. (1964) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(64)90253-x · Cited by 117
Similar Functions of Uric Acid and Ascorbate in Man ?
Proctor, P. H. (1970) · Nature · doi:10.1038/228868a0 · Cited by 111
Matsushita, S., Ibuki, F., & Aoki, A. (1963) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(63)90253-4 · Cited by 68
Smith, R. C., & Lawing, L. F. (1983) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(83)90582-9 · Cited by 63
[19] Uric acid: Functions and determination
Hochstein, P., Hatch, L., & Sevanian, A. (1984) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(84)05022-9 · Cited by 44
Self-citationMutagenic activity of ascorbate in mammalian cell cultures
Rosin, M. P., San, R. H. C., & STICH, H. F. (1980) · Cancer Letters · doi:10.1016/0304-3835(80)90145-7 · Cited by 43
Mechanism of the inhibitory action of phenelzine on microsomal drug metabolism.
Muakkassah-Kelly, S. F., & Yang, W. (1981) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)32773-4 · Cited by 32
Self-citationMeasurement of uric acid, ascorbic acid, and related metabolites in biological fluids
Hatch, L., & Sevanian, A. (1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90816-9 · Cited by 32
Self-citationEvidence for a direct interaction of l-ascorbate with rat liver DNA
Jamaluddin, M. A., Rajalakshmi, S., & Sarma, D. S. R. (1981) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(81)90199-4 · Cited by 9
Flagged first, then by citations
Research works printed but not linked: 5
- Pryor, W. A. (ed.) (1981) Free Radicals in Biology, vols. 1-5, Academic Press, New York
- Ames, B. N., Cathcart, R., Schwiers, E. & Hochstein, P. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6858-6862
- Weber, G. (1948) Trans. Faraday Soc. 44, 185-196
- Albert, A. (1973) Selective Toxicity, pp. 282-391, Chapman and Hall, London 18. Hatch, L. L. & Sevanian, A. (1984) Anal. Biochem. 138, 324-328
- Haber, R. & Weiss, J. J. (1934) Proc. R. Soc. London Ser. A 147, 332-351
Cited by
Sorted by citations
Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production
Powers, S. K., & Jackson, M. J. (2008) · Physiological Reviews · doi:10.1152/physrev.00031.2007 · Cited by 2,459
Method for the measurement of antioxidant activity in human fluids
Koraćević, D., Koracevic, G., Djordjevic, V., Andrejevic, S., & Cosic, V. (2001) · Journal of Clinical Pathology · doi:10.1136/jcp.54.5.356 · Cited by 1,986
Oxygen radicals and human disease
CROSS, C. E., HALLIWELL, B., BORISH, E. T., PRYOR, W. A., AMES, B. N., SAUL, R. L., McCORD, J. M., & HARMAN, D. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-107-4-526 · Cited by 1,856
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?
Johnson, R. J., Kang, D., Feig, D. I., Kivlighn, S. D., Kanellis, J., Watanabe, S., Tuttle, K. R., Rodríguez‐Iturbe, B., Herrera-Acosta, J., & Mazzali, M. (2003) · Hypertension · doi:10.1161/01.hyp.0000069700.62727.c5 · Cited by 1,354
Metadata
- Authors
- Davies, K. J. A., Sevanian, A., Muakkassah-Kelly, S. F., & Hochstein, P.
- Affiliations
- University of Southern California (US)
- ORCID
- Davies, K J A
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1986-05-01
- Volume
- 235
- Issue
- 3
- Pages
- 747-754
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1146751
- OpenAlex
- W1832537945
- Cited by
- 558
- References
- 20
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 19 · 2023: 23 · 2022: 18 · 2021: 25 · 2020: 22 · 2019: 11 · 2018: 20 · 2017: 19 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 23 · 2012: 23
- FWCI
- 17.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ES-03785, ES03466, ES03598)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Keywords
- uric acid, antioxidant function, iron(III) coordination, ascorbic acid oxidation, lipid peroxidation, binding constant, oxygen free radicals, singlet oxygen
- MeSH terms
- Animals, Ascorbic Acid, Hydrogen-Ion Concentration, Iron, Liposomes, Male, Microsomes, Liver, Organometallic Compounds, Oxidation-Reduction, Rats, Inbred Strains, Uric Acid, Macromolecular Substances, Lipid Metabolism, Rats
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
