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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Norcocaine and N-hydroxynorcocaine formation in human liver microsomes: role of cytochrome P-450 3A4.

Cocaine was metabolized to norcocaine by microsomes prepared from lymphoblastoid cells expressing transfected human P-450 3A4. The specific activities of norcocaine formation by microsomes prepared from three human liver samples correlated with the amount of P-450 3A immunoreactive protein detected by immunoblot. Triacetyloleandomycin, a specific inhibitor of P-450 3A isoforms, inhibited formation of norcocaine from cocaine, but not formation of N-hydroxynorcocaine from norcocaine. The chemical identity of the norcocaine and N-hydroxynorcocaine produced by human liver microsomes was established by combination of gas chromatography and mass spectrometry. Thus, human P-450 3A4 is a cocaine demethylase, and P-450 isoforms of the 3A family are responsible for the majority of norcocaine production by human hepatic microsomes.[1]

References

  1. Norcocaine and N-hydroxynorcocaine formation in human liver microsomes: role of cytochrome P-450 3A4. LeDuc, B.W., Sinclair, P.R., Shuster, L., Sinclair, J.F., Evans, J.E., Greenblatt, D.J. Pharmacology (1993) [Pubmed]
 
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