Biosynthesis of papaverine

Tracer experiments have shown that in Papaver somniferum papaverine arises from (−)-norreticuline via norlaudanidine and norlaudanosine.     

Purification and Characterization of Calmodulins from Papaver somniferum and Euphorbia lathyris

Calmodulins (CaM) were isolated and characterized from two well-known latex producing plants, Papaver somniferum and Euphorbia lathyris. The molecular weights of both were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 17,000 comparable to that of bovine brain CaM. Amino acid compositions also compared similarly with those of known CaMs, with regard to the presence of trimethyllysine and the ratio of phenylalanine to tyrosine. The Cornish-Bowden equation (SΔn) revealed strong statistical correlations of P. somniferum and E. lathyris CaM with those of other plants and animals, although their amino acid compositions were not identical. Both plant CaM stimulated CaM dependent cAMP phosphodiesterase: for Papaver somniferum the K_a was found to be 1.09 nanomolar and for Euphorbia lathyris, 2.01 nanomolar.     

Alkaloidal storage,metabolism and translocation in the vesicles of Papaver somniferum latex

After centrifuging stem and capsule latex of Papaver somniferum at 1000 g, 95–99% of the alkaloids were found in the pellet, which consists m     

Biotransformation of thebaine by cell suspension cultures of Papaver somniferum cv. Marianne

Thebaine is biotransformed to neopine by cell suspension cultures of Papaver somniferum cv. Marianne grown in O-B5 medium. Results of precursor stu     

Conversion of codeine to morphine in isolated capsules of Papaver somniferum

The biotransformation of codeine to morphine was studied in isolated capsules of Papaver somniferum. Cofactors such as nicotinamide adenine dinucleotide, adenosine 5′-triphosphate, S-acetyl coenzyme A and pyridoxal phosphate were not required in the conversion of codeine to morphine. Reducing agents such as dithiothreitol, glutathione and β-mercaptoethanol strongly promoted codeine and morphine degradation, while morphine formation remained at a constant level. Hydrogen peroxide (concentration > 0.25 mM) caused the conversion of codeine and morphine to N-oxides by non-enzymatic oxidation. Isolated capsules of P. somniferum provide a method of studying the biotransformation of codeine to morphine.     

Morphinane alkaloids in cultured tissues and redifferentiated organs of Papaver somniferum

The capacity of alkaloid synthesis was examined in cultured tissues of Papaver somniferum. Callus, derived meristemoids, redifferentiated roots and     

Bound morphine and codeine in the capsule of Papaver somniferum

The polysaccharide fraction of the capsule of Papaver somniferum contained bound morphine and codeine. The alkaloids appear to be bound to the polymer by two different types of linkage.     

Papaver bracteatum,potential commercial source of codeine

Papaver bracteatum, native to Iran and southern Russia, has been grown successfully in many countries. Research in the northwest United States has confirmed the potential for its commercial production as a source of the alkaloid thebaine. Potential for the chemical conversion of thebaine into codeine, one of man’s most widely used alkaloidal medicinal agents, is reviewed. Economic and social advantages of growing this species over opium poppy (Papaver somniferum) are discussed. The value of the seed oil for cooking and industrial use is considered.     

Enzymic reduction of codeinone in vitro cell-free systems from Papaver somniferum and P. Bracteatum

Cell-free extracts have been prepared from Papaver somniferum which catalyze the reduction of codeinone-[16-³H] to codeine. The methodology for examining this conversion has pointed to conditions for exploring the preparation of suitable enzyme extracts. P. bracteatum also yielded a cell-free system which reduced codeinone to codeine, both of which are foreign to this species.     

Oxidation of tyrosine by Papaver somniferum latex

The polyphenolase complex isolated from the organelles which sedimented at 1000 g from the latex of Papaver somniferum was found to be composed of soluble and mernbrane-bound fractions. Partial purification resolved two polyphenolases, only one of which utilized tyrosine, a probable precursor of the alkaloid morphine. Activity of these two polyphenolase fractions was shown to change during the development of the capsule.     

Synthesis of [3-14C]-2′-methylreticuline and its incorporation into alkaloid fractions of Papaver somniferum

[3-¹⁴C]-2′-Methylreticuline has been synthesized by standard methods. This modified opium alkaloid precursor is efficiently incorporated by aberrant biosynthesis into alkaloid fractions of Papaver somniferum, particularly into a highly purified codeine fraction.     

Bound forms of alkaloids in Papaver somniferum and P. Bracteatum

The polysaccharide fraction of the pericarp and seed of Papaver somniferum were shown to contain bound forms of morphine which were derived from radioactive morphine fed to living plants. Bound forms of codeine, thebaine and some unidentified alkaloid-like compounds were also detected in the pericarp and bound thebaine occurred in the pericarp of Papaver bracteatum. The complexity and molecular weight of the bound alkaloids seemed to increase during ripening, and it is suggested that these substances represent transitional forms in the metabolism and transiocation of morphine from latex to seed.     

Peroxidases of Papaver somniferum

Extracts of Papaver somniferum that had peroxidase activity were ineffective in catalysing oxidation of reticuline. Two peroxidases were purified from young seedlings and their properties examined. Only one of them was active toward indole-3-acetic acid (IAA).     

In vitro conversion of morphine to its N-oxide in Papaver somniferum latex

Radio active morphine (¹⁴C- and ³H-labelled) was fed in vitro to freshly collected samples of capsules and stem latex of Papaver somniferum and it was shown that some of it was converted to radioactive N-oxide. Although metabolic activity and variation between samples of latex collected at different times were much less marked than those previously found using in vivo methods, the results do confirm that the isolated latex is a metabolically viable tissue.     

The Ultrastructure of the Alkaloidal Vesicles of Papaver somniferum latex

Papaver somniferum latex contains abundant small vesicles. Theirultrastructure was studied in tissue sections from adult plantsand in sections of sequential fractions of centrifuged latex.The vesicles were found to exist in two forms, the first witha smooth but progressively granulated outer membrane and thesecond, probably derived from the first, with adherent ‘cap-like’structures which in the heavier centrifuged fractions possesseda zonally-ordered interior. These vesicle fractions were active in synthesizing morphineand the name ‘alkaloidal vesicle’ is proposed forthem. Papaver somniferum latex also contains an organelle whichwas found to resemble a complex organelle present in the latexof Hevea brasiliensis. Its function is not yet known.     

Biotransformation of (RS)-reticuline and morphinan alkaloids by cell cultures of Papaver somniferum

(RS)-Reticuline was stereospecifically converted to (—)-(S)-scoulerine and (—)-(S)-cheilanthifoline by cell cultures of Papaver somniferum and (—)-(R)-reticuline was recovered as an optical pure compound by racemic resolution. (—)-Codeinone was converted in high yield to (—)-codeine in both cell culture and enzyme preparation, but the other morphinans, thebaine, codeine and morphine, were not metabolized.     

Involvement of lipoxygenase in elicitor-stimulated sanguinarine accumulation in Papaver somniferum suspension cultures

The involvement of lipoxygenase (LOX, EC 1.13.11.12) in elicitor-induced opium poppy defense response was investigated. Papaver somniferum L. suspension cultures were treated with abiotic elicitor methyl jasmonate (MJ), fungal elicitor (Botrytis cinerea homogenate) and phenidone (specific inhibitor of LOX) to determine the involvement of this enzyme in production of sanguinarine, the major secondary metabolite of opium poppy cultures. P. somniferum suspension cultures responded to elicitor treatment with strong and transient increase of LOX activity followed by sanguinarine accumulation. LOX activity increased in elicited cultures, reaching 9.8 times of the initial value at 10 h after MJ application and 2.9 times after B. cinerea application. Sanguinarine accumulated to maximal levels of 169.5 ± 12.5 μg g^?1 dry cell weight in MJ-elicited cultures and 288.0 ± 10.0 μg g^?1 dry cell weight in B. cinerea-elicited cultures. The treatment of cells with phenidone before elicitor addition, significantly reduced sanguinarine production. The relative molecular weight of P. somniferum LOX (83 kDa) was estimated by using immunobloting and its pH optimum was shown to be pH 6.5.