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a pathway for morphine biosynthesis

Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex.

Finally, resemblance of the mammalian pathway to morphine biosynthesis in plants is discussed.

We determined for NMT and the best BIQ substrate, (R)-norreticuline, an apparent Km of 0.9 mM, which is three times lower than the one described for tryptamine, the previously chatacterized substrate of NMT []. This newly observed characteristic of an enzyme, for which a role in human physiology has not yet been assigned, to accept only one enantiomer of a precursor of mammalian morphine biosynthesis may suggest a new in vivo function of NMT. We investigated this hypothesis further by injecting (i.p.) (R)-THP into mice with subsequent urine analysis by HR-LC-MS. In a previous study, salutaridine was found in urine of mice after injection (i.p.) of racemic, deuterium labeled THP []. We confirm now that salutaridine is also excreted by mice injected (i.p.) with the enantiomer (R)-THP. This finding provides conclusive evidence that the living animal is capable of forming morphine precursors from (R)-configured BIQ alkaloids and suggests that the initial steps as well as the enzymatic sequence yielding (R)-reticuline may proceed stereochemically differently than in the plant pathway.

30/12/1993 · Review Article

Detection of substrate binding motifs for morphine biosynthetic pathway intermediates in novel wound inducible (R,S)-reticuline 7 …

Morphine occurs in substantial amounts only in one single plant species, in Papaver somniferum the opium poppy, while in certain mammals it seems to occur widespread but in very small quantities [–]. Recently, the capability of living animals to form morphine de novo was elucidated []. The biosynthesis of morphine in mammals has been suggested to start with tetrahydropapaveroline (THP), a simple BIQ alkaloid, yielding the first morphinan alkaloid salutaridine by four enzymatic reactions: two O-methylation reactions at C6, C4′, one N-methylation and one phenol coupling reaction. However, it is not known if these initial steps occur with (S)-configured substrates as has been shown for the plant pathway.

The L-Arginine-Nitric Oxide Pathway

are unable to produce morphine or codeine carry mutations in the STORR gene that inhibit the morphine production pathway.

There are two metabolic pathways that create terpenoids: Mevalonic acid pathway
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