Human Cells Make Morphine

BIOCHEMISTRY

It turns out that opium poppies aren't the only organisms that can make morphine. New results reveal that human cells can also biosynthesize this powerful analgesic.

Traces of morphine have been previously isolated from various animal tissues and fluids, including human heart and urine. However, whether this morphine is endogenous--that is, made by the body--or from dietary sources had not been established.

Now, Meinhart H. Zenk, Chotima Poeaknapo, and coworkers at the Biocenter at Martin Luther University Halle-Wittenberg and the Leibniz Institute of Plant Biochemistry, both in Halle, Germany, report that human cells are able to synthesize morphine [Proc. Natl. Acad. Sci. USA, 101, 14091 (2004)]. The role of endogenous morphine is still not known, but it may be involved in the functioning of the immune, vascular, and nervous systems.

The researchers verified that morphine was biosynthesized by feeding cultures of human nerve and pancreas cells with isotopically labeled precursors, including ¹⁸O₂ and ¹³C-tyramine. Both types of cells produce morphine precursors, but only the nerve cells produce morphine.

As measured by mass spectrometry, the morphine produced by cells grown in ¹⁸O₂ is four mass units higher than it would be if they had been grown in ¹⁶O₂, indicating the presence of two ¹⁸O atoms. The positions of the labeled oxygen atoms indicate that they are incorporated in the morphine through tyramine.

The study is a "nice verification" of endogenous morphine formation in human cells, according to George B. Stefano, director of the Neuroscience Research Institute at the State University of New York, Old Westbury, who also studies morphine in animals. "Now one must study endogenous morphine within the context of addiction, since [addiction] studies basically are concerned with exogenous opiate administration."