Reaction of hematin with allylic fatty acid hydroperoxides: identification of products and implications for pathways of hydroperoxide-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene.
Reaction of hematin with allylic fatty acid hydroperoxides: identification of products and implications for pathways of hydroperoxide-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene.
复制标题
血红素与烯丙基脂肪酸氢过氧化物的反应：产物的鉴定以及对7,8-二羟基-7,8-二氢苯并[a]芘的氢过氧化物依赖性环氧化途径的影响。
DOI：
10.1021/bi00418a059
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Marnett,LJ
中科院分区：
文献类型：
--
作者：
Labeque,R;Marnett,LJ
Regine La Beque和Lawrence J.Marnett*化学系，韦恩州立大学，底特律，密歇根州48202，收到1987年12月8日；修订稿件收到1988年4月14日摘要：在含吐温20的磷酸盐缓冲液中，10-羟基-8-烯酸(10-OH-18：！)(50微米)与血红素(0.5微米)反应生成10-氧代-8-烯酸、10-氧代-8-烯酸(10-氧代-10：L)和10-羟基-8-烯酸，相对产率分别为79%、4%和17%。1 mM的丁基羟基苯甲醚不影响产物的形态和相对分布。大约5%的过氧化氢从10-位异构化到8-位。10-氧-10：L很可能是通过中间体烷氧基/3-裂解为醛和-辛基而产生的。为了验证这一点，在相同的条件下，10-羟基过氧十八碳-8，12-二烯酸与血液反应。合成了10-氧代-8，12-二烯酸、10-氧代-8-烯酸和10-羟基-8，12-二烯酸，相对收率分别为50%、45%和5%。产物比例随时间和过氧化氢与催化剂的比例保持不变，不受酚类抗氧化剂的影响。10-氧代-10：L的产量高于10-哦-18：2。这是由于中间体烷氧基从前者到共振态稳定的辛烯基有较高的/3-裂解速率。2-辛烯基与02反应的两个产物辛烯醛和辛烯醇以10%的产率与10-氧-10：L反应。7，8-二羟基-7，8-二氢苯并[a]芘(BP-7，8-二醇)的包合导致了10-OH18：！与同位素标记的过氧化氢或02的研究表明，大约65%的环氧化物氧来自02，35%来自氢过氧化氢氧，这与过氧化自由基作为氧化剂的参与是一致的。现有证据表明，血红素将脂肪酸氢过氧化还原为烷氧基，烷氧基被氧化为酮，还原为醇，或经历/3-裂解为醛。在这些反应中产生的碳自由基与02偶联，产生过氧基自由基，使BP-7，8-二醇环氧化。过氧化氢引起的环氧化反应的比例较小，可能是由于过氧化氢氧化成过氧基，或过氧化氢异源裂解成酒精和铁氧络合物。自然界中，脂肪酸氢过氧化物会通过脂质过氧化产生(Tappl，1973；Bus&Gibson，1979；Svingen等，1979)或前列腺素和白三烯的生物合成(Hamberg&Samuelsson，1974；Samuelsson等，1978；Gardner，1980；Samuelsson，1983)。在哺乳动物组织中也分离到了烷基过氧化氢，如tRNA1“116的组成成分过氧Y-碱(Feinberg等人，1974)和黄素氧化酶的中间体4a-氢过氧黄素(Kemal&Bruice，1976)。烷基过氧化氢是一种温和的氧化剂，可由过渡金属和金属蛋白转化为各种强大但短暂的氧化剂(Dunford&Stillman，1976；White等人，1980；Lee&Bruice，1985；McMurry&Groves，1986；Marnett等人，1986；Vaz&Coon，1987)。这种氧化剂可能会导致外源生物
Regine La beque and Lawrence J. Marnett* Department of Chemistry, Wayne State University, Detroit, Michigan 48202 Received December 8, 1987; Revised Manuscript Received April 14, 1988 abstract: Reaction of 10-hydroperoxyoctadec-8-enoic acid (10-OOH-18:!)(50 µ) with hematin (0.5 µ) in sodium phosphate buffer containing Tween 20 (200 µ) generates 10-oxooctadec-8-enoic acid, 10-oxodec-8-enoic acid (10-oxo-10: l), and 10-hydroxyoctadec-8-enoic acid in relative yields of 79, 4, and 17%, respectively. The productprofile and relative distribution are unaffected by 1 mM butylated hydroxyanisole. Approximately 5% of the hydroperoxide isomerizes from the 10-to the 8-position. 10-Oxo-10: l most likely arises via/3-scission of an intermediate alkoxyl radical to the aldehyde and the «-octyl radical. To test this, 10-hydroperoxyoctadeca-8, 12-dienoic acid was reacted with hematinunder identical conditions. 10-Oxooctadeca-8, 12-dienoic acid, 10-oxodec-8-enoic acid, and 10-hydroxyoctadeca-8, 12-dienoic acid are formed in relative yields of 50, 45, and 5%, respectively. The product ratios are constant with time and hydroperoxide to catalyst ratio and unaffected by inclusion of phenolic antioxidants. The higher yield of 10-oxo-10: l from 10-OOH-18: 2 compared to 10-OOH-18:! is due to the higher rate of/3-scission of the intermediate alkoxyl radical from the former to the resonance-stabilized octenyl radical. Two products of reaction of the 2-octenyl radical with 02, octenal and octenol, were detected in 10% yield relative to 10-oxo-10: l. Inclusion of 7, 8-dihydroxy-7, 8-dihydrobenzo [a] pyrene (BP-7, 8-diol) led to epoxidation by both 10-OOH-18:! and 10-OOH-18: 2. Studies with isotopically labeled hydroperoxide or 02 indicated approximately 65% of the epoxide oxygen was derived from 02 and 35% from hydroperoxide oxygen, consistent with the involvement of peroxyl free radicals as the oxidizing agents. The available evidence indicates that hematin reduces the fatty acid hydroperoxides homolytically to alkoxyl radicals that are oxidized to ketones, reduced to alcohols, or undergo/3-scission to aldehydes. Carbon radicals generated during these reactions couple to 02, generating peroxyl free radicalsthat epoxidize BP-7, 8-diol. The smaller percentage of epoxidation that results from hydroperoxide oxygen may arise from oxidation of the hydroperoxide group to peroxyl radicals or from heterolytic cleavage of the hydroperoxide to alcohol and an iron-oxo complex.Fatty acid hydroperoxides arise in nature by lipid per-oxidation (Tappel, 1973; Bus & Gibson, 1979; Svingen et al., 1979) or during prostaglandin and leukotriene biosynthesis (Hamberg & Samuelsson, 1974; Samuelsson et al., 1978; Gardner, 1980; Samuelsson, 1983). Alkyl hydroperoxides such as peroxy-Y-base, a component of tRNA1” 116 (Feinberg et al., 1974), and 4a-hydroperoxyflavin, an intermediate in flavin oxidase (Kemal & Bruice, 1976), havealso been isolatedin mammalian tissue. Alkyl hydroperoxides are mild oxidizing agents that are converted by transition metals and metalloproteins to a variety of powerful but transient oxidants (Dunford & Stillman, 1976; White et al., 1980; Lee & Bruice, 1985; McMurry & Groves, 1986; Marnett et al., 1986; Vaz & Coon, 1987). Such oxidants maycontribute to xenobiotic
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血红素和多不饱和脂肪酸氢过氧化物对 7,8-二羟基-7,8-二氢苯并[a]芘的自由基环氧化
DOI：
--
发表时间：
1981
期刊：
影响因子：
--
作者：
T. Dix;L. Marnett
通讯作者：
L. Marnett
DOI：
--
发表时间：
1979
期刊：
影响因子：
--
作者：
H. Chan;G. Levett;J. A. Matthew
通讯作者：
J. A. Matthew
DOI：
10.1073/pnas.73.10.3381
发表时间：
1976-10
影响因子：
11.1
作者：
D. Thakker;H. Yagi;A. Y. Lu;W. Levin;A. Conney
通讯作者：
D. Thakker;H. Yagi;A. Y. Lu;W. Levin;A. Conney
DOI：
10.1016/s0021-9258(17)39362-6
发表时间：
1985-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Ortiz de Montellano;C E Catalano
通讯作者：
P. Ortiz de Montellano;C E Catalano
肝微粒体脂质氢过氧化物对胆固醇的环氧化。
DOI：
--
发表时间：
1982
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
T. Watabe;M. Isobe;A. Tsubaki
通讯作者：
A. Tsubaki