MPS 587 - Advanced Plant Biochemistry Course Fall Semester 2011

MPS 587 - Advanced Plant Biochemistry Course
Fall Semester 2011
Lecture 21
Alkaloids III
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Phenylethylamine alkaloids
Purine alkaloids
Betalains
Acridone alkaloids
Colchicine
Camalexin
Disclaimer
As part of the alkaloid biosynthesis section of this lecture, I will cover various
illicit uses and share some stories of people who have used extracts and
preparations containing mind-altering alkaloids.
Herewith I would like to state very clearly that this is not meant to play down
the dangers associated with the illicit use of drugs, nor do I support in any way
the use of such materials.
B.M. Lange
(Course director)
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Phenylethylamine alkaloids
Source: Wikipedia
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Mescaline
Source: Wikipedia
• Occurs naturally in the peyote cactus (Lophophora williamsii), the San Pedro cactus (Echinopsis
pachanoi), in the Peruvian Torch cactus (Echinopsis peruviana), and it is also found in a number of other
members of the Cactaceae.
• Extract from peyote in Native American religious ceremonies has been noted since the earliest
European contact, notably by the Huichols in Mexico.
• Effective human dosage is 200–400 milligrams (3.75 mg/kg), with the effects lasting for up to twelve hours;
users typically experience intensifications and alterations of existing stimuli (objects and sounds), not the
appearance of non-existent fanciful objects or actions that the user believes are real (in this regard these are not
true hallucinations and thus different from LSD); often experienced as pleasurable and illuminating but
occasionally as accompanied by feelings of anxiety or revulsion; not physically addictive.
Famous users
Jerry Garcia
Aldous Huxley
Ernst Juenger
Jim Morrison
Carlos Castaneda
Allen Ginsberg
Timothy Leary
Jean-Paul Sartre
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Ephedrine
Source: Wikipedia
• Derived from various plants in the genus Ephedra (family Ephedraceae). It is most usually marketed in the
hydrochloride and sulfate forms.
• In traditional Chinese medicine, the herb ma huang (Ephedra sinica) contains ephedrine as its principal active
constituent.
• The principal mode of action of ephedrine is to displace noradrenaline from storage vesicles in presynaptic
neurons. The displaced noradrenaline is released into the neuronal synapse where it is free to activate the
postsynaptic adrenergic receptors.
• Ephedrine was once widely used as a topical decongestant and as a bronchodilator in the treatment for asthma. It
continues to be used for these indications, although its popularity is waning due to the availability of more
effective agents for these indications which exhibit fewer adverse effects.
• As a phenylethylamine, ephedrine has a similar chemical structure to amphetamines. Ephedrine can be used in the
synthesis of methamphetamine by chemical reduction; this has made ephedrine a highly sought-after chemical
precursor in the illicit manufacture of methamphetamine.
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Purine alkaloids
Source: Wikipedia
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Purine alkaloid biosynthesis
(Ashihara et al. (2008) Phytochemistry 69, 841)
Xanthosine (precursor
of purine alkaloids) is
produced via at least
four
routes:
from
adenosine
released
from the SAM cycle
(SAM route); from IMP
originating from de
novo purine synthesis
(de novo route), from
the cellular adenine
nucleotide pool (AMP
route) and from the
guanine
nucleotide
pool (GMP route).
(1) 7-methylxanthosine synthase (xanthosine N-methyltransferase); (2) N-methylnucleosidase; (3) theobromine synthase
(monomethylxanthine N-methyltransferase); (4) caffeine synthase (dimethylxanthine N-methyltransferase); (3–4) dualfunctional caffeine synthase (EC 2.1.1.160). Several N-methyltransferases with different substrate specificities contribute
to the conversion of xanthosine to caffeine. Recent observations suggest that steps 1 and 2 are catalysed by xanthosine Nmethyltransferase.
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Betalains
(Strack et al. (2003) Phytochemistry 62, 247)
Betalains are a group of water-soluble chromoalkaloids (red-violet
betacyanins and yellow betaxanthins), which occur only in certain
members of the plant order Caryophyllales (e. g. red beet) and
some higher fungi (e. g. fly agaric).
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Betalain biosynthesis
(Tanaka et al. (2003) The Plant Journal 54, 733)
The biosynthetic pathways consist of several enzymatic
reaction steps and spontaneous chemical reaction steps.
DOPA formation is catalyzed by tyrosine hydroxylase
(enzyme I), betalamic acid formation by DOPA 4,5dioxygenase (DOD; enzyme II), cDOPA formation by
plant PPO or DOPA oxidase (enzyme III), conjugation of
betalamic acid and amino acid, amine or cDOPA by
enzyme VIII, and modification with sugar molecules and
aliphatic or aromatic compounds by enzymes IV–VII.
Although DOPA is an important precursor not only of
betalains but also of various secondary metabolites in
plants, there have only been a few reports about the
partial purification of tyrosine hydroxylase from P.
grandiflora. cDOPA is presumably synthesized from
DOPA by the action of PPO, but there is no direct
evidence to prove it in vitro except correlation of the
accumulation of PPO mRNA and betacyanin contents in
tissues of pokeweed (Phytolacca americana).
The condensation step of betalamic acid and amino
acid, amine or cDOPA probably occurs as a spontaneous
chemical reaction in vivo.
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Acridone alkaloids
Source: Wikipedia
Rue (Ruta graveolens) has been used as a medicinal and
"antimagic" herb for centuries. It was considered a reliable
defense against witches.
Artists, including Michelangelo and Leonardo da Vinci, improved
their creativity and eyesight by ingesting rue.
Rue is a symbol of regret, sorrow and repentance, and Catholics
used sprigs of it to sprinkle holy water on worshippers.
The rue leaf was the model for the suit of clubs in playing cards.
Rue was formerly used to treat almost every ailment known to
Man, but its effectiveness and safety are questionable.
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Colchicine
Source: Wikipedia
Extracted from plants of the genus Colchicum (Autumn crocus). Originally used to treat
rheumatic complaints and gout, it was also prescribed for its cathartic and emetic effects.
Colchicine inhibits microtubule polymerization by binding to tubulin. Apart from inhibiting
mitosis, a process heavily dependent on cytoskeletal changes, it also inhibits neutrophil motility
and activity, leading to a net anti-inflammatory effect.
Since chromosome segregation is driven by microtubules, colchicine is also used for inducing
polyploidy in plant cells. Doubling a normal (diploid) watermelon results in a tetraploid plant
(one having four sets of chromosomes). When the tetraploid plant is bred back, or pollinated,
by a diploid or normal plant, the resulting seed produces a triploid plant that is basically a
"mule" of the plant kingdom, and it produces seedless watermelons.
Autumnaline
Demecolcine (R = Me)
Colchicine (R = Ac)
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O-Methylandrocymbine
Camalexin biosynthesis in Arabidopsis thaliana
(Glawischnig (2007) Phytochemistry 68, 401)
Camalexin originates from tryptophan and its biosynthesis
involves the cytochrome P450 enzymes CYP79B2 and
CYP71B15 (PAD3). Camalexin induction is a complex process,
for which triggering by reactive oxygen species (ROS),
salicylic acid signalling, and the glutathione status are
important. Targets of the signalling cascade are the
tryptophan and camalexin biosynthetic genes, which are
strongly transcriptionally upregulated at the sites of
pathogen infection.
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