Endogenous formation of morphine in human cells

How human neuroblastoma cells make morphine

“…However, in mammals, norlaudanosoline has been detected on few occasions: in rat striatum (15), human brain (16), a human pancreatic cell line (1), and humans treated with various pharmacological agents, for instance alcohol and L-dopa (17). In agreement with these findings, we have proven the endogenous origin of norlaudanosoline in human cell cultures by our previous experiments showing position specific labeling with 18 O and norlaudanosoline being part of the (S)-reticuline pathway in DAN-G cells (1).…”

“…Moreover, the potential precursor alkaloids norlaudanosoline (tetrahydropapaveroline) and (S)-reticuline, which were also produced by these cells, were shown to be labeled with two atoms of 18 O (1). In a separate set of experiments, application of [ring- 13 C 6 ]tyramine, (S)-[1-13 C,N-13 CH 3 ]reticuline, and [N-C 2 H 3 ]thebaine to SH-SY5Y cells yielded specific incorporation into endogenous morphine (1). With these experiments, we unequivocally proved that human neuroblastoma cells are capable of synthesizing morphine.…”

“…Trace amounts have been detected in various tissues of mammals and lower animals and have been identified by MS or even NMR (summarized in ref. 1). However, the origin of the endogenous morphine has been a matter of controversy, because morphine also was found in hay, lettuce, human milk, and cow's milk as well as in commercial rat and rabbit feed (2)(3)(4).…”

Reflexiones sobre la Biosíntesis de la Morfina y el Parkinson Idiopático

“…Se ha encontrado morfina en varias especies de animales y en particular en las ratas de laboratorio y en el hombre (6). Poeaknapo (7) ha demostrado su síntesis endógena mas allá de las dudas sembradas por la propuesta de que la morfina hallada en la leche (8), provenía de las lechugas, o del heno, y las analizó en ambiente separado para evitar la presencia de trazas de morfina en sus laboratorios (7). El grupo que mayor cantidad de publicaciones ha realizado sobre morfina en animales lo lidera Stefano (9).…”

Heterologous expression, purification, crystallization and preliminary X-ray analysis of raucaffricine glucosidase, a plant enzyme specifically involved inRauvolfiaalkaloid biosynthesis

“…This is particularly true for the two largest alkaloid families, the isoquinolines and the monoterpenoid indole alkaloids, which consist of about 6000 and 2000 structurally different members, respectively. In the first family several examples have been investigated: for example, the biosynthesis of berberine or morphine (Zenk, 1995;Poeaknapo et al, 2004;Boettcher et al, 2005). The antiarrhythmic Rauvolfia alkaloid ajmaline together with its derivatives is the best representative of the indole alkaloid family .…”