Week 5

Question 1

Concentrations of plant toxins vary due to

Answer 1

• plant age and genetics
• climatic and soil differences
• between various plant parts

Question 2

Phytotoxin Class

Answer 2

Alkaloids, Phenols, Glycosides, Oxalates, Psoralens, Terpenes, Glycoproteins/lectins

Question 3

What do Alkaloids have in common?

Answer 3

• Organic
• Amino Nitrogen containing
• Basic (alkaline)
• Bitter taste
• Form salts after being dissolved in dilute acid

Question 4

Colchicine

Answer 4

2º metabolite
Colchicine arrests cell division at metaphase

Inhibits microtubule polymerization
by binding to tubulin one of the main constituents of microtubules
* Availability of tubulin is essential to mitosis – colchicine acts as a
“mitotic poison” or spindle poison

Question 5

Strychnine

Answer 5

• Blocks the inhibitory strychnine-
  sensitive glycine receptor (GlyR),
  a ligand-gated chloride channel in the spinal cord and brain
• Stimulant at a dose of 1.1-6.4 mg
• Causes convulsions

Question 6

Coniine (Hemlock)

Answer 6

neurotoxin; partial
cholinergic agonist structurally similar to nicotine
* Disrupts CNS function
* Causes death by blocking the neuromuscular junction (like curare)
* Eventual paralysis of the respiratory muscles which results in death due to
lack of oxygen to heart and brain

Question 7

Toxicity of pyrrolizidine alkaloids

Answer 7

Pyrrolizidine alkaloids (PAs) are metabolised to reactive X-linking
pyrroles -> hepatotoxic
* They may cause onset of hepatic veno-occlusive disease (VOD)
* Some PAs are also tumourigenic
* Some PAs cause pulmonary toxicity

Question 8

PA: essential features for hepatotoxicity

Answer 8

The potential of PA compounds as
hepatotoxins is governed by certain minimum structural features
(“toxicophores”):
1. an unsaturated 3-pyrroline ring
2. one or two hydroxyl groups each attached to the pyrroline ring
3. one or preferably two esterified groups
4. presence of a branched chain on the acid moiety

Question 9

Phenols

Answer 9

Most widely distributed group of phytochemicals
* Classes: Phenols, Coumarins, Flavonoids, Anthraquinones
* Effects via estrogenic activity & on clotting mechanisms
(vitamin K analogues)

Question 10

Cardiac glycosides

Answer 10

Digitoxin: Exert their effects by inhibiting the Na +/K +-ATPase pump
-> rise in intracellular Na +, Ca ++ concentration
-> increased force of myocardial muscle contractions
* Overdose results in cardiac arrhythmias

Question 11

Psoralens

Answer 11

It is phototoxic by UV activation to form DNA photoadducts
- so is widely used in PUVA (Psoralen + UVA) treatment for psoriasis, eczema, vitiligo & cutaneous T-cell lymphoma

Question 12

Phorbol esters

Answer 12

Phorbol myristate acetate (PMA) is a tricyclic diterpene in croton oil
– it is a potent tumour promoter
* PMA mimics diacylglycerol (DAG) to
activate protein kinase C (PKC) and stimulate cell proliferation

Question 13

Lectins: Ricin

Answer 13

Contains highly toxic lectins Ricin I & II -> causes death if passes through gut wall (usually destroyed intestinally)

• Ricin’s B chain binds to
  galactose on cell surface
  and triggers endocytosis
• Ricin A chain kills cells by
  inactivating the 60s
  ribosomal subunit
  (the glycosidase enzyme
  removing Adenine from
  28S rRNA loop)

Question 14

Traditional Chinese Medicine toxicity

Answer 14

Can be due to direct toxicity, misidentification,
substitution, contamination, adulteration and
drug interactions

Question 15

Aflatoxins

Answer 15

Structurally diverse natural polysubstituted coumarins
* The four major aflatoxins are B1 , B 2 , G1 and G2
B = blue fluorescence
G = green fluorescence
* Aflatoxin B 1 is most liver-toxic; via CYP metabolism to epoxide
* Aflatoxins are strongly
implicated in serious
toxicity in humans
and animals

Question 16

Tetrodotoxin

Answer 16

Highly specific blocker of
Na + transport across cell
membranes

Question 17

Function and nature of venom

Answer 17

• Facilitates food capture or defence
• Digestive – contains digestive enzymes
• e.g. hyaluronidase
• helps to distribute venom
• Venom in general is a complex mixture
• toxins, vehicles, distributors, digestors
• Venom has to be fast acting
• to immobilise prey

Question 18

Venom production

Answer 18

Venom generally secreted by epithelial cells of
specialised exocrine glands
* Stored in a receptacle or venom sac

Question 19

Action of venom

Answer 19

• Typically kill by paralysis of respiratory muscles
• Progressive paralysis leading to hypoxia and
  death
• Different venoms affect different parts of the
  neuromuscular system
• Cardiovascular system effects
• Anaphylactic shock
• Coagulation system of blood another target
• anticoagulation - bleeding
• induction of coagulation - thrombosis
• Muscle action
• Most Australian snake venoms are myolytic (except Textilan
  from brown snake)
• e.g. highly myolytic Notexin from tiger snakes
   damage to muscle tissue
   release of myoglobin
   blocks kidneys (myoglobinuria)
  Nerve Fibres
• Blockade of nerve conduction
• Tetrodotoxin (TTX) stabilise nerve membranes
• Inhibit the movement of sodium ions effectively
  stopping action potentials
• Spontaneous action potentials
• Atraxotoxin from the venom of funnel-web spiders (Atrax spp.), causes firing of nerve impulses
  producing gross muscle twitching
• In some tissues, the release of catecholamines with consequent lachrymation and salivation