OXIDATIVE METABOLISM OF SOME HYDRAZINE DERIVATIVES BY RAT LIVER AND LUNG TISSUE FRACTIONS
OXIDATIVE METABOLISM OF SOME HYDRAZINE DERIVATIVES BY RAT LIVER AND LUNG TISSUE FRACTIONS
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DOI：
10.1002/jbt.2570010106
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发表时间：
1986-01-01
期刊：
影响因子：
--
通讯作者：
PROUGH R A
中科院分区：
文献类型：
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作者：
ERIKSON J M;PROUGH R A
酶系统在大鼠肝脏和肺负责肼衍生物的氧化代谢进行了研究，以确定这些酶，细胞色素P-450和单胺氧化酶，是否负责代谢激活肼致癌/有毒代谢产物。细胞色素P-450优先氧化1，2-二取代肼和酰肼的氮-氮键，而单胺氧化酶氧化所有测试的肼衍生物类的氮-氮键。氮到氮键的氧化导致在1，2-二取代肼的情况下形成稳定的偶氮中间体，并且在单取代肼和酰肼的情况下形成不稳定的单偶氮（二氮烯）代谢物。此外，细胞色素P-450优先氧化单烷基肼的碳-氮键，该反应形成醛代谢物（通过腙中间体）。单取代肼被证明是线粒体单胺氧化酶的有效的、不可逆的抑制剂。相反，1，2-二取代肼似乎是单胺氧化酶的良好底物，并在高浓度下作为竞争性抑制剂。在单烷基肼、乙基肼和正丙基肼的1，2-二取代肼的代谢中似乎没有任何单胺氧化酶同工酶（A型或B型）特异性。
The enzyme systems in rat liver and lung responsible for the oxidative metabolism of hydrazine derivatives were studied to determine whether these enzymes, cytochrome P-450 and monoamine oxidase, were responsible for metabolically activating hydrazines to carcinogenic/toxic metabolites. Cytochrome P-450 preferentially oxidized the nitrogen to nitrogen bond of 1,2-disubstituted hydrazines and hydrazides, while monoamine oxidase oxidized the nitrogen to nitrogen bond of all the classes of hydrazine derivatives that were tested. Oxidation of the nitrogen to nitrogen bond led to the formation of stable azo intermediates in the case of 1,2-disubstituted hydrazines and to unstable monoazo (diazene) metabolites in the case of monosubstituted hydrazines and hydrazides. In addition, cytochrome P-450 preferentially oxidized the carbon to nitrogen bond of monoalkylhydrazines, this reaction in the formation of aldehyde metabolites (via hydrazone intermediates). Monosubstituted hydrazines were shown to be potent, irreversible inhibitors of mitochondrial monoamine oxidase. In contrast, the 1,2-disubstituted hydrazines appeared to be good substrates for the monoamine oxidase and served as competitive inhibitors at high concentrations. There did not appear to be any monoamine oxidase isozyme (form A or B) specificity in the metabolism of either the 1,2-disubstituted hydrazines of the monoalkylhydrazines, ethyl- and n-propylhydrazine.