PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH.
Abstract
Purified PGH synthase when acting on arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate generated superoxide in burst-like fashion. In eight experiments using different batches of enzyme, the mean +/- SE rate of superoxide generation from 100 U of enzyme measured as the superoxide dismutase-inhibitable reduction of cytochrome c was 5.06 +/- 0.19 nmol/min in the first minute and 0.35 +/- 0.03 nmol/min subsequently. Optimum rates of superoxide were seen at concentrations of reduced nicotinamide-adenine dinucleotide in excess of 80 microM and reduced nicotinamide-adenine dinucleotide 3'-phosphate in excess of 100 microM. Using prostaglandin G2 or linoleic acid as substrate rather than arachidonate also resulted in superoxide generation. When prostaglandin H2 was used as substrate, no superoxide was generated. The rate of superoxide generation was markedly inhibited by cyclooxygenase inhibitors. Superoxide generation was also observed during the action of lipoxygenase on either linoleic or arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate but not in their absence. Indomethacin had no effect on superoxide generation from lipoxygenase. We conclude that PGH synthase and lipoxygenase produce superoxide via a side-chain reaction dependent on the presence of suitable reducing cosubstrate. This mechanism is analogous to that described for peroxidases in general.
Integrity signals
Registry
Cites
Statistics
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?
The red blood cell expresses a functional eNOS that contributes in part to systemic blood pressure responses.
“a number of recent studies using chimeric cross bone marrow transplant mouse models have shown that the red blood cell also expresses a functional eNOS that contributes in part to systemic blood pressure responses”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [536]
Cites
Isolation and Structure of Two Prostaglandin Endoperoxides That Cause Platelet Aggregation
Hámberg, M., Svensson, J. E., Wakabayashi, T., et al. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.2.345 · Cited by 998 · see citing works
Superoxide‐dependent production of hydroxyl radical catalyzed by iron—EDTA complex
McCord, J. M., & Day, E. D. (1978) · FEBS Letters · doi:10.1016/0014-5793(78)80116-1 · Cited by 870 · see citing works
Purification of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes.
Miyamoto, T., Ogino, N., Yamamoto, S., & Hayaishi, O. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33534-2 · Cited by 663 · see citing works
Mechanism for irreversible self-deactivation of prostaglandin synthetase.
Egan, R. W., Paxton, J., & Kuehl, F. A. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32853-3 · Cited by 588 · see citing works
Ellis, E. F., Oelz, O., Roberts, L. J., et al. (1976) · Science · doi:10.1126/science.959827 · Cited by 498 · see citing works
Self-citationEvidence for a peroxide-initiated free radical mechanism of prostaglandin biosynthesis.
Hemler, M. E., & Lands, W. E. M. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43731-3 · Cited by 471 · see citing works
Gutteridge, J. M. C., Rowley, D. A., & Halliwell, B. B. (1981) · Biochemical Journal · doi:10.1042/bj1990263 · Cited by 467 · see citing works
Superoxide production in experimental brain injury
Kontos, H. A., & Wei, E. P. (1986) · Journal of neurosurgery · doi:10.3171/jns.1986.64.5.0803 · Cited by 421 · see citing works
Self-citationvan der Ouderaa, F. J., Buytenhek, M., Nugteren, D. H., et al. (1977) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(77)90008-x · Cited by 417 · see citing works
Wei, E. P., Dietrich, W. D., Povlishock, J. T., Navari, R. M., & Kontos, H. A. (1980) · Circulation Research · doi:10.1161/01.res.46.1.37 · Cited by 291 · see citing works
Self-citationKontos, H. A., Wei, E. P., Ellis, E. F., Jenkins, L. W., Povlishock, J. T., Rowe, G. T., & Hess, M. L. (1985) · Circulation Research · doi:10.1161/01.res.57.1.142 · Cited by 291 · see citing works
Self-citationSuperoxide‐dependent formation of hydroxyl radicals in the presence of iron salts
Flitter, W. D., Rowley, D. A., & Halliwell, B. B. (1983) · FEBS Letters · doi:10.1016/0014-5793(83)80602-4 · Cited by 281 · see citing works
Cerebral Arteriolar Damage by Arachidonic Acid and Prostaglandin G 2
Kontos, H. A., Wei, E. P., Povlishock, J. T., Dietrich, W. D., Magiera, C. J., & Ellis, E. F. (1980) · Science · doi:10.1126/science.7403881 · Cited by 245 · see citing works
Self-citationWei, E. P., Kontos, H. A., Dietrich, W. D., et al. (1981) · Circulation Research · doi:10.1161/01.res.48.1.95 · Cited by 222 · see citing works
Self-citationOxygen radicals mediate the cerebral arteriolar dilation from arachidonate and bradykinin in cats.
Kontos, H. A., Wei, E. P., Povlishock, J. T., & Christman, C. W. (1984) · Circulation Research · doi:10.1161/01.res.55.3.295 · Cited by 215 · see citing works
Self-citationTischler, M. E., Friedrichs, D., Coll, K. E., & WILLIAMSON, J. R. (1977) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(77)90346-0 · Cited by 209 · see citing works
Co-oxygenation of organic substrates by the prostaglandin synthetase of sheep vesicular gland.
Marnett, L. J., Wlodawer, P., & Samuelsson, B. O. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)40789-8 · Cited by 207 · see citing works
Wei, E. P., Kontos, H. A., Christman, C. W., DeWitt, D. S., & Povlishock, J. T. (1985) · Circulation Research · doi:10.1161/01.res.57.5.781 · Cited by 202 · see citing works
Self-citationStudies on Cytochrome c Peroxidase
Yonetani, T., Schleyer, H., & Ehrenberg, A. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96523-3 · Cited by 183 · see citing works
Rollins, T. E., & Smith, W. L. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85577-1 · Cited by 172 · see citing works
Ellis, E. F., Wright, K. F., Wei, E. P., & Kontos, H. A. (1981) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1981.tb04476.x · Cited by 168 · see citing works
Self-citationOgino, N., Ohki, S., Yamamoto, S., & Hayaishi, O. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34657-4 · Cited by 164 · see citing works
The spectra of the enzyme-substrate complexes of catalase and peroxidase
Chance, B. (1952) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(52)90469-4 · Cited by 164 · see citing works
Reduction of hydroperoxides in the prostaglandin biosynthetic pathway by a microsomal peroxidase.
Egan, R. W., Gale, P. H., & Kuehl, F. A. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50758-4 · Cited by 160 · see citing works
Spectral properties of the higher oxidation states of prostaglandin H synthase.
Lambeir, A., Markey, C. M., Dunford, H. B., & Marnett, L. J. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95676-0 · Cited by 159 · see citing works
George, P. (1952) · Nature · doi:10.1038/169612a0 · Cited by 154 · see citing works
Land, E. J., & Swallow, A. J. (1971) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(71)90126-5 · Cited by 154 · see citing works
Increased phospholipase C activity after experimental brain injury
Wei, E. P., Lamb, R. G., & Kontos, H. A. (1982) · Journal of neurosurgery · doi:10.3171/jns.1982.56.5.0695 · Cited by 146 · see citing works
Self-citationYokota, K., & Yamazaki, I. (1977) · Biochemistry · doi:10.1021/bi00628a024 · Cited by 145 · see citing works
Roberts, J. E., Hoffman, B. M., Rutter, R., et al. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69747-4 · Cited by 143 · see citing works
Mechanism of cerebral arteriolar abnormalities after acute hypertension
Kontos, H. A., Wei, E. P., Dietrich, W. D., et al. (1981) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1981.240.4.h511 · Cited by 132 · see citing works
Self-citationYokota, K., & Yamazaki, I. (1965) · Biochimica et Biophysica Acta (BBA) - Enzymology and Biological Oxidation · doi:10.1016/s0926-6593(65)80154-0 · Cited by 129 · see citing works
Effects of oxygen radicals on cerebral arterioles
Wei, E. P., Christman, C. W., Kontos, H. A., et al. (1985) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1985.248.2.h157 · Cited by 128 · see citing works
Self-citationOxidation reactions by prostaglandin cyclooxygenase-hydroperoxidase.
Egan, R. W., Gale, P. H., Baptista, E. M., et al. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68970-2 · Cited by 123 · see citing works
Marnett, L. J., Bienkowski, M. J., & Pagels, W. R. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50562-7 · Cited by 67 · see citing works
Hoffman, B. M., Roberts, J. E., Brown, T. G., et al. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.12.6132 · Cited by 62 · see citing works
In vitro O2 uptake and histochemical fiber type of resting hamster muscles
Sullivan, S. M., & Pittman, R. N. (1984) · Journal of Applied Physiology · doi:10.1152/jappl.1984.57.1.246 · Cited by 40 · see citing works
Chapter 5 Enzymes in the arachidonic acid cascade
Yamamoto, S. (1983) · New comprehensive biochemistry · doi:10.1016/s0167-7306(08)60537-2 · Cited by 24 · see citing works
Effects of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE) on cerebral arterioles of cats
Christman, C. W., Wei, E. P., Kontos, H. A., et al. (1984) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1984.247.4.h631 · Cited by 12 · see citing works
Self-citationReduction in cerebral arteriolar oxygen consumption by arachidonate
Levasseur, J. E., Kontos, H. A., & Ellis, E. F. (1985) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1985.248.4.h534 · Cited by 8 · see citing works
Self-citationHYDROGEN PEROXIDE, OXYGEN, SUPEROXIDE ANION, SINGLET OXYGEN AND PEROXIDASE
Dunford, H. B. (1979) · Elsevier eBooks · doi:10.1016/b978-0-12-164380-5.50015-3 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases
Bhattacharyya, A., Chattopadhyay, R., Mitra, S., & Crowe, S. E. (2014) · Physiological Reviews · doi:10.1152/physrev.00040.2012 · Cited by 2,484 · see citing works
β-Amyloid-mediated vasoactivity and vascular endothelial damage
Thomas, T., Thomas, G., McLendon, C., Sutton, T., & Mullan, M. (1996) · Nature · doi:10.1038/380168a0 · Cited by 703 · see citing works
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Interactions of oxidants with vascular signaling systems
Wolin, M. S. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.6.1430 · Cited by 463 · see citing works
Baker, C. S. R., Hall, R. J. C., Evans, T. J., Pomerance, A., Maclouf, J., Creminon, C., Yacoub, M. H., & Polak, J. M. (1999) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.19.3.646 · Cited by 296 · see citing works
Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke
Rink, C., & Khanna, S. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3474 · Cited by 233 · see citing works
Reactive oxygen species and the control of vascular function
Wolin, M. S. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01167.2008 · Cited by 133 · see citing works
Walkowski, B., Kleibert, M., Majka, M., & Wojciechowska, M. (2022) · Cells · doi:10.3390/cells11091553 · Cited by 117 · see citing works
- Authors
- Kukreja, R. C., Kontos, H. A., Hess, M. L., & Ellis, E. F.
- ORCID
- Kukreja, R C
- Venue
- Circulation Research
- Published
- 1986-12
- Volume
- 59
- Issue
- 6
- Pages
- 612-619
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2117909173
- Cited by
- 487
- References
- 41
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 13 · 2013: 8 · 2012: 13
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL21851, HL-24917)
- National Institute of Neurological Disorders and Stroke (NS-19316)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- prostaglandin H synthase, lipoxygenase, superoxide production, NADH, NADPH, arachidonic acid, prostaglandin G2, linoleic acid, cyclooxygenase inhibitors, indomethacin, prostaglandin H2
- MeSH terms
- Arachidonic Acids, Linoleic Acids, Lipoxygenase, NAD, NADP, Oxygen Consumption, Prostaglandin-Endoperoxide Synthases, Superoxides, Arachidonic Acid, Linoleic Acid
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
