Abstract
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 resulted 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 or the monoalkylhydrazines, ethyl- and n-propylhydrazine.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 41-52 |
| Number of pages | 12 |
| Journal | Journal of Biochemical Toxicology |
| Volume | 1 |
| Issue number | 1 |
| State | Published - Mar 1986 |
| Externally published | Yes |
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Cite this
Oxidative metabolism of some hydrazine derivatives by rat liver and lung tissue fractions. / Erikson, John M; Prough, R. A.
In: Journal of Biochemical Toxicology, Vol. 1, No. 1, 03.1986, p. 41-52.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxidative metabolism of some hydrazine derivatives by rat liver and lung tissue fractions.
AU - Erikson, John M
AU - Prough, R. A.
PY - 1986/3
Y1 - 1986/3
N2 - 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 resulted 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 or the monoalkylhydrazines, ethyl- and n-propylhydrazine.
AB - 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 resulted 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 or the monoalkylhydrazines, ethyl- and n-propylhydrazine.
UR - http://www.scopus.com/inward/record.url?scp=0022672080&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022672080&partnerID=8YFLogxK
M3 - Article
C2 - 3271870
AN - SCOPUS:0022672080
VL - 1
SP - 41
EP - 52
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
SN - 1095-6670
IS - 1
ER -