Oxidative Conversion of Carotenoids to Retinoids and Other Products
Open accessAbstract
In vertebrates, provitamin A carotenoids are converted to retinal by beta-carotene-15,15'-dioxygenase. The enzyme activity is expressed specifically in intestinal epithelium and in liver. The intestinal enzyme not only plays an important role in providing animals with vitamin A, but also determines whether provitamin A carotenoids are converted to vitamin A or circulated in the body as intact carotenoids. We have found that a high fat diet enhanced the beta-carotene dioxygenase activity together with the cellular retinol binding protein type II level in rat intestines. Flavonols with a catechol structure in the B-ring and 2,6-di-tert-butyl-4-methylphenol inhibited the dioxygenase activity of pig intestinal homogenates and the conversion of beta-carotene to retinol in Caco-2 human intestinal cells. Thus, the bioavailability of dietary provitamin A carotenoids might be modulated by the other food components ingested. Regulation of the dioxygenase activity and its relation to the retinoid metabolism as well as to lipid metabolism deserve further study. In contrast to enzymatic cleavage, it is known that both retinal and beta-apocarotenals are formed in vitro from beta-carotene by chemical transformation, which cleaves conjugated double bonds at random positions under various oxidative conditions. Moreover, recent studies have indicated that the oxidation products formed by chemical transformation might have specific actions on the proliferation of certain cancer cells. We have found that lycopene, a typical nonprovitamin A carotenoid, was cleaved in vitro to acycloretinal, acycloretinoic acid and apolycopenals in a nonenzymatic manner, and that the mixture of oxidation products of lycopene induced apoptosis of HL-60 human promyelocytic leukemia cells. Thus, it is worth evaluating the formation of oxidation products and their biological actions, in order to elucidate the underlying mechanisms of the beneficial effects of carotenoids on human health.
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
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?
Nagao found that oxidized metabolites of lycopene but not lycopene itself can inhibit cell growth and stimulate apoptosis in HL-60.
“Nagao [81] found that oxidized metabolites of lycopene but not lycopene itself can inhibit cell growth and stimulate apoptosis in a different cell line (HL-60).”
From The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes (2016) · cites this paper as [81]
Lycopene in human prostate cancer cells inhibited cell growth, but the oxidized mixtures displayed markedly more potent growth inhibition.
“In another study, lycopene in human prostate cancer cells inhibited cell growth, but the oxidized mixtures displayed markedly more potent growth inhibition [81, 82].”
From The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes (2016) · cites this paper as [81]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Dietary Factors That Affect the Bioavailability of Carotenoids
van het Hof, K. H., Weststrate, J. A., West, C. E., & Hautvast, J. G. A. J. (2000) · The Journal of Nutrition · doi:10.1093/jn/130.3.503 · Cited by 776 · see citing works
Khachik, F., Spangler, C. J., Smith, J. C., Canfield, L. M., Steck, A., & Pfander, H. (1997) · Analytical Chemistry · doi:10.1021/ac961085i · Cited by 535 · see citing works
Filling the Gap in Vitamin A Research
von Lintig, J., & Vogt, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.11915 · Cited by 449 · see citing works
Intestinal absorption and tissue distribution of carotenoids
Furr, H. C., & Clark, R. M. (1997) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(97)00060-0 · Cited by 364 · see citing works
Wang, X.-D., Liu, C., Bronson, R. T., Smith, D. E., Krinsky, N. I., & Russell, R. M. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.1.60 · Cited by 356 · see citing works
Olson, J. A., & Hayaishi, O. (1965) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.54.5.1364 · Cited by 342 · see citing works
Biosynthesis of Vitamin A with Rat Intestinal Enzymes
Goodman, D. S., & Huang, H. S. (1965) · Science · doi:10.1126/science.149.3686.879 · Cited by 263 · see citing works
Sugawara, T., Kushiro, M., Zhang, H., Ono, H., Nagao, A., & Nara, E. (2001) · Journal of Nutrition · doi:10.1093/jn/131.11.2921 · Cited by 240 · see citing works
Self-citationWang, X., Tang, G., Fox, J. G., Krinsky, N. I., & Russell, R. M. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90322-a · Cited by 229 · see citing works
Cloning and Expression of β,β-Carotene 15,15′-Dioxygenase
Wyss, A., Wirtz, G., Woggon, W. ‐., Brugger, R., Wyss, M., Friedlein, A., Bachmann, H., & Hunziker, W. H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2619 · Cited by 217 · see citing works
Oxidative degradation of β-carotene and β-apo-8′-carotenal
Mordi, R. C., Walton, J. C., Burton, G. W., et al. (1993) · Tetrahedron · doi:10.1016/s0040-4020(01)80333-1 · Cited by 165 · see citing works
Stimulation of Gap Junctional Communication: Comparison of acyclo-Retinoic Acid and Lycopene
Stahl, W., von Laar, J., Martin, H., Emmerich, T., & Sies, H. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1510 · Cited by 162 · see citing works
Isolation and identification of singlet oxygen oxidation products of .beta.-carotene
Stratton, S. P., Schaefer, W. H., & Liebler, D. C. (1993) · Chemical Research in Toxicology · doi:10.1021/tx00034a024 · Cited by 149 · see citing works
Enzymatic formation of 9‐ cis , 13‐ cis , and all‐trans retinals from isomers of β‐carotene
Nagao, A., & Olson, J. A. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.12.8088462 · Cited by 116 · see citing works
Self-citationNara, E., Hayashi, H., Kotake, M., Miyashita, K., & Nagao, A. (2001) · Nutrition and Cancer · doi:10.1207/s15327914nc392_18 · Cited by 100 · see citing works
Self-citationGradelet, S., Leclerc, J., Siess, M. H., & Astorg, P. O. (1996) · Xenobiotica · doi:10.3109/00498259609052493 · Cited by 100 · see citing works
Stoichiometric Conversion ofall trans-β-Carotene to Retinal by Pig Intestinal Extract
Nagao, A., During, A., Hoshino, C., et al. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0142 · Cited by 98 · see citing works
Self-citationSalgo, M. G., Cueto, R., Winston, G. W., & Pryor, W. A. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00172-5 · Cited by 92 · see citing works
Formation of cleavage products by autoxidation of lycopene
Kim, S., Nara, E., Kobayashi, H., et al. (2001) · Lipids · doi:10.1007/s11745-001-0706-8 · Cited by 87 · see citing works
Assay of β-Carotene 15,15′-Dioxygenase Activity by Reverse-Phase High-Pressure Liquid Chromatography
During, A., Nagao, A., Hoshino, C., & Terao, J. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0400 · Cited by 84 · see citing works
Self-citationDevery, J. M., & Milborrow, B. V. (1994) · British Journal Of Nutrition · doi:10.1079/bjn19940042 · Cited by 65 · see citing works
During, A., Nagao, A., & Terao, J. (1998) · Journal of Nutrition · doi:10.1093/jn/128.10.1614 · Cited by 63 · see citing works
Self-citationLakshman, M., Mychkovsky, I., & Attlesey, M. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.23.9124 · Cited by 58 · see citing works
Nikawa, T., Schulz, W. A., Vandenbrink, C. E., et al. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1089 · Cited by 55 · see citing works
Characterization of Metabolites of Astaxanthin in Primary Cultures of Rat Hepatocytes
Wolz, E., Liechti, H., Notter, B., et al. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)15207-5 · Cited by 51 · see citing works
Suruga, K., Suzuki, R., Goda, T., & Takase, S. (1995) · Journal of Nutrition · doi:10.1093/jn/125.8.2039 · Cited by 46 · see citing works
Retinoid Metabolism During Intestinal Absorption
Ong, D. E. (1993) · Journal of Nutrition · doi:10.1093/jn/123.suppl_2.351 · Cited by 45 · see citing works
Carotenoid oxidative degradation products inhibit Na+-K+-ATPase
Siems, W. G., Sommerburg, O., Hurst, J. S., & van Kuijk, F. J. G. M. (2000) · Free Radical Research · doi:10.1080/10715760000300961 · Cited by 45 · see citing works
Inhibition of β-carotene-15,15′-dioxygenase activity by dietary flavonoids
Nagao, A., Maeda, M., Lim, B. P., Kobayashi, H., & Terao, J. (2000) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(00)00090-5 · Cited by 44 · see citing works
Self-citationHu, X., White, K. M., Jacobsen, N. E., Mangelsdorf, D. J., & Canfield, L. M. (1998) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(98)00048-5 · Cited by 38 · see citing works
Duitsman, Barua, Becker, et al. (1999) · International Journal for Vitamin and Nutrition Research · doi:10.1024/0300-9831.69.5.303 · Cited by 30 · see citing works
Mochizuki, K., Suruga, K., Kitagawa, M., et al. (2001) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2305 · Cited by 25 · see citing works
McClure, T. D., & Liebler, D. C. (1995) · Chemical Research in Toxicology · doi:10.1021/tx00043a017 · Cited by 19 · see citing works
Isolation and Identification of a Major Urinary Canthaxanthin Metabolite in Rats
Bausch, Liechti, Oesterhelt, et al. (1999) · International Journal for Vitamin and Nutrition Research · doi:10.1024/0300-9831.69.4.268 · Cited by 16 · see citing works
[19] Retinoic acid synthesis from β-carotene in Vitro
Napoli, J. L. (1993) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(93)14066-r · Cited by 12 · see citing works
Carotenoid photodegradation products and human peripheral blood mononuclear cell function
Rahman, A., & Parker, R. S. (2001) · Nutrition Research · doi:10.1016/s0271-5317(01)00274-3 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biomarkers in nutritional epidemiology: applications, needs and new horizons
Jenab, M., Slimani, N., Bictash, M., Ferrari, P., & Bingham, S. A. (2009) · Human Genetics · doi:10.1007/s00439-009-0662-5 · Cited by 448 · see citing works
Antioxidant and pro-oxidant activities of carotenoids and their oxidation products
Ribeiro, D., Freitas, M., Silva, A. M. S., Carvalho, F., & Fernandes, E. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.07.060 · Cited by 280 · see citing works
Hantz, H. L., Young, L. F., & Martin, K. R. (2005) · Experimental Biology and Medicine · doi:10.1177/153537020523000303 · Cited by 124 · see citing works
The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes
Ascenso, A., Pedrosa, T., Pinho, S., Pinho, F., Oliveira, J. M. P. F. D., Cabral Marques, H., Oliveira, H., Simões, S., & Santos, C. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8214631 · Cited by 57 · see citing works
van Steenwijk, H. P., Bast, A., & de Boer, A. (2020) · Molecules · doi:10.3390/molecules25194378 · Cited by 41 · see citing works
- Authors
- Nagao, A.
- Affiliations
- Food Research Institute (JP)
- Corresponding author
- Nagao, Akihiko
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 134
- Issue
- 1
- Pages
- 237S-240S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W1918723691
- Cited by
- 119
- References
- 36
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 8
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Agriculture, Forestry and Fisheries
- Bio-oriented Technology Research Advancement Institution
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- carotenoid oxidation, vitamin A metabolism, provitamin A carotenoids, intestinal epithelium, flavonols, 2,6-di-tert-butyl-4-methylphenol, lycopene, apoptosis, HL-60 cells, carotenoid bioavailability, high-fat diet, retinal
- MeSH terms
- Animals, Biological Availability, Carotenoids, Diet, Dietary Fats, Humans, Intestines, Liver, Oxidation-Reduction, Oxygenases, Retinoids, Vitamin A, beta Carotene, beta-Carotene 15,15'-Monooxygenase
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
