Fe(III)-Lipoxygenase Converts Its Suicide-Type Inhibitor Octadeca-9,12-diynoic Acid into 11-Oxooctadeca-9,12-diynoic Acid

Nieuwenhuizen, W.; Schilstra, Maria J.; Hoof, Anca van der Kerk-van; Brandsma, L.; Veldink, Gerrit A.; Vliegenthart, Johannes F.G.

doi:10.1021/bi00033a028

Cited by 16 publications

(34 citation statements)

References 35 publications

(47 reference statements)

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“…At the highest ODYA concentrations, the amount of 11-oxo-ODYA had decreased to approximately 5% of the amount that was formed at 40 µM ODYA. GC/MS analysis of the reaction mixtures revealed no evidence for reaction products other than 11-oxo-ODYA [see Nieuwenhuizen et al (1995)]. …”

Section: Resultsmentioning

confidence: 99%

“…Triple-bond analogues of polyunsaturated fatty acids have been known as inactivators of lipoxygenase since 1965, and their inactivating potential has been investigated by a number of authors (Blain & Shearer, 1965;Downing et al, 1970Downing et al, , 1972Hammerström, 1977;Corey & Munroe, 1982;Corey & Park, 1982;Kühn et al, 1984Kühn et al, , 1991Shieh et al, 1985;Corey, 1987;Borel et al, 1993;Nieuwenhuizen et al, 1995). It was shown in several of these studies that triple-bond analogues are enzymatically converted by lipoxygenase.…”

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confidence: 99%

“…The product 11-HP-EEYA appeared to decompose nonenzymatically into 11-oxo-EEYA. We observed that octadeca-9,12-diynoic acid (ODYA) was converted into 11-oxooctadeca-9,12-diynoic acid (11-oxo-ODYA) upon treatment with Fe(III)-lipoxygenase (Nieuwenhuizen et al, 1995).…”

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confidence: 99%

“…It has been firmly established that inactivation occurs only in the presence of O 2 (Corey & Park, 1982;Kühn et al, 1984;Shieh et al, 1985;Nieuwenhuizen et al, 1995). Furthermore, only Fe(III)-lipoxygenase is susceptible to inactivation by ODYA, whereas Fe(II)-lipoxygenase is hardly affected by this inhibitor (Nieuwenhuizen et al, 1995). Linoleic acid protects lipoxygenase against inactivation by ETYA (Kühn et al, 1984).…”

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confidence: 99%

“…Hydroxyl radicals, superoxide anions, and H 2 O 2 are not involved in the inactivation (Kühn et al, 1984). 11-oxo-ODYA binds covalently to solvent-exposed amino groups of the protein, but this modification did not cause inactivation either (Nieuwenhuizen et al, 1995). However, Shieh et al (1985) observed that one of the conversion products of EEYA, 11-HP-EEYA, can irreversibly inactivate lipoxygenase.…”

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Mechanism of Lipoxygenase Inactivation by the Linoleic Acid Analogue Octadeca-9,12-diynoic Acid

et al. 1996

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During the irreversible inactivation of soybean Fe(III)-lipoxygenase [Fe(III)-LOX] by octadeca-9,12-diynoic acid (ODYA), significant quantities of 11-oxooctadeca-9,12-diynoic acid (11-oxo-ODYA) are formed [Nieuwenhuizen, W. F., et al. (1995) Biochemistry 34, 10538-10545]. To elucidate the inactivation mechanism, a quantitative study into the relationship between the inactivation and 11-oxo-ODYA formation was carried out. The following observations were made. (1) LOX (0.84 µM) was completely inactivated by 10 to 80 µM ODYA. However, at ODYA concentrations greater than 100 µM, LOX was only partially inactivated, and there was no inactivation at all at ODYA concentrations above 750 µM. The average number of turnovers in which 11-oxo-ODYA was formed increased from 1.2 to 12 when the ODYA concentration increased from 1 to 50 µM and then decreased again to 1.2 at 1000 µM ODYA. (2) The enzyme that was not irreversibly inactivated by ODYA was in the Fe(III) form at ODYA concentrations below 10 µM but in the Fe(II) form at ODYA concentrations greater than 100 µM. (3) In the presence of 750 µM ODYA and 25 µM 13(S)-hydroperoxy-

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Mechanism of Lipoxygenase Inactivation by the Linoleic Acid Analogue Octadeca-9,12-diynoic Acid

et al. 1996

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Oxidation in Living Cells and its Chemical Models

2002

Activation and Catalytic Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes

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Robust inhibitory effects of conjugated linolenic acids on a cyclooxygenase-related linoleate 10S-dioxygenase: Comparison with COX-1 and COX-2

Mashhadi

Boeglin

Brash

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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There are many reports of the anti-inflammatory, anti-cancer, and anti-atherosclerotic activities of conjugated linolenic acids (cLNA). They constitute a small percentage of fatty acids in the typical human diet, although up to 80% of the fatty acids in certain fruits such as pomegranate. In the course of studying a bacterial fatty acid dioxygenase (Nostoc linoleate 10S-DOX, an ancient relative of mammalian cyclooxygenases), we detected strong inhibitory activity in a commercial sample of linoleic acid. We identified two cLNA isomers, β-eleostearic (9E,11E,13E-18:3) and β-calendic acid (8E,10E,12E-18:3), as responsible for that striking inhibition with a Ki of ~49 nM and ~125 nM, respectively, the most potent among eight cLNA tested. We also examined the effects of all eight cLNA on the activity of COX-1 and COX-2. Jacaric acid (8Z,10E,12Z-18:3) and its 12E isomer, 8Z,10E,12E-18:3, strongly inhibit the activity of COX-1 with a Ki of ~1.7 and ~1.1 μM, respectively. By contrast, COX-2 was ≤ 30% inhibited at 10μM concentrations of the cLNA. Identifying the activities of the naturally occurring fatty acids is of interest in terms of understanding their interaction with the enzymes, and for explaining the mechanistic basis of their biological effects. The study also highlights the potential presence of inhibitory fatty acids in commercial lipids prepared from natural sources. Analysis of seven commercial samples of linoleic acid by HPLC and UV spectroscopy is illustrated as supplementary data.

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Fe(III)-Lipoxygenase Converts Its Suicide-Type Inhibitor Octadeca-9,12-diynoic Acid into 11-Oxooctadeca-9,12-diynoic Acid

Cited by 16 publications

References 35 publications

Mechanism of Lipoxygenase Inactivation by the Linoleic Acid Analogue Octadeca-9,12-diynoic Acid

Mechanism of Lipoxygenase Inactivation by the Linoleic Acid Analogue Octadeca-9,12-diynoic Acid

Oxidation in Living Cells and its Chemical Models

Robust inhibitory effects of conjugated linolenic acids on a cyclooxygenase-related linoleate 10S-dioxygenase: Comparison with COX-1 and COX-2

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