Abstract
Studies of factors affecting the assay for N-demethylation of the narcotic drug meperidine by a combined microsome plus supernatant fraction of rat liver have been made. By use of a loose homogenizer, higher buffer concentration in the homogenizing solution and a higher substrate concentration, activity 6- to 8-fold greater than that previously reported has been obtained.
Starvation of rats for as little as 16 hours reduces N-demethylation of meperidine by rat liver to zero.
The N-demethylation activity of starved rat liver microsome plus supernatant fraction can be restored to unstarved control levels by addition of sufficient glucose 6-phosphate or isocitrate. Glucose 1-phosphate and glycogen are also effective.
Microsomes prepared from the liver of rats starved 16 hours are strongly inhibitory to demethylation of meperidine by normal rat liver. This inhibition is not reversed by addition of glucose 6-phosphate or isocitrate, but may be reversed by addition of high levels of TPN and nicotinamide.
Some properties of the N-demethylation inhibitor associated with microsomes prepared from starved rat liver have been investigated and from the available evidence, the inhibition may be due to a specific TPNase or a TPN inactivator of a nonspecific nature. The implication of the above results for detoxication in vivo and for general detoxication reactions is discussed.
Footnotes
- Received July 21, 1960.
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