|Abstract or Summary
- An aspect of the metabolism of monoalkylhydrazines has been
investigated using both intact rats and rat liver microsomal enzyme
Intact rats respired propane and n-butane on administration of 0.3-0.5 mmoles of isopropyl- and n-butylhydrazine, respectively.
Based upon dose administered, a five to ten percent
yield of hydrocarbon was obtained.
In vitro experiments were conducted to further characterize the
The conversion of alkylhydrazines to alkanes occurred
predominantly in the microsomal fraction of liver cells.
All of the
simple monoalkylhydrazines, methyl-, ethyl-, n-propyl-, isopropyl-
and n-butylhydrazine , were converted to the corresponding alkanes at
a rate of ca. 20 mμmoles/120 min/10 mg of microsomal protein.
Other substrates yielding methane were the azo derivative of Procarbazine (N-isopropyl-α-[2- methylhydrazino]-p-toluamide),
azoxy derivative of Procarbazine and
The reaction specifically required oxygen, NADPH and liver microsomes.
Rat and guinea pig microsomal preparations converted the
alkylhydrazines to alkanes at a rate higher than bovine, porcine and
ovine microsomal preparations.
Various parameters typical of enzyme reactions indicated that
the reaction was enzymic.
The apparent Michaelis constant for
ethylhydrazine was found to be 4.5 x
with a maximal enzyme
velocity of 32.0 mμmoles of ethane/120 min/10 mg of microsomal
The enzymic reaction was linear with time to 120 min, with
microsomal protein to 10 mg and with NADPH to 30 μmoles.
enzyme inhibitors, p-chloromercuribenzoate
caused 50% inhibition at
carbon monoxide, chelating agents and a mixed-function oxidase inhibitor (SKF 525-A) had no great effect on the enzyme reaction.
Cytochromes b₅ and P₄₅₀ did not appear to play a role in the
The lack of correlation between loss of enzyme activity
and cytochrome content during tryptic digestion, lack of enzyme in-
duction with P₄₅₀ induction by phenobarbital and 3-methylcholanthrene administration and lack of correlation between b₅ content
enzyme activity on lipase solubilization indicate strongly
that cytochrome P₄₅₀ and b₅ are not required for alkylhydrazine oxidase activity.
Only a marginal purification could be performed.
A methylhydrazine derivative, Procarbazine, was converted to
the azo derivative with the same microsomal preparations and conditions.
The possibility of an alkyldiazene (alkyldiimide) intermediate