August 25, 2015

How the cell makes morphine

Vanderbilt investigators have discovered how mammals, including humans, produce the painkiller morphine.

by Sanjay Mishra


Morphine is one of the strongest known painkillers. Although initially isolated and still produced from the opium poppy, it is also produced in low concentrations by mammals, including humans.

The exact role of this endogenous morphine is unknown, but it is hypothesized to play a role in infection, inflammation and possibly neurological disorders such as Parkinson’s disease and schizophrenia.

How animal cells make morphine has not been well understood, although iron-containing enzymes are thought to be involved in both animals and plants. However, the instability of the biochemical intermediates has made it difficult to demonstrate the last steps involved.

Now in a recent publication in the Journal of Biological Chemistry, F. Peter (Fred) Guengerich, Ph.D., and colleagues establish, in mammals, the critical steps in the conversion of the chemical precursor thebaine into morphine.

They demonstrate that the enzymes cytochrome P450 3A4 and cytochrome P450 3A5 convert thebaine into morphine by removing methyl groups, a demethylation pathway that is very different from that in plants.

This research was supported by the National Institutes of Health (grants CA090426, ES007028).

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