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NATURAL PRODUCTS PLANT & ANIMAL TOXINS

NATURAL PRODUCTS PLANT & ANIMAL TOXINS. PLANT TOXINS. RICIN. Small protein, 2 polypeptides (short A chain, larger B chain) linked by disulphide bridge B chain links ricin to outside of cell via galactose in a glycoprotein

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NATURAL PRODUCTS PLANT & ANIMAL TOXINS

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  1. NATURAL PRODUCTS PLANT & ANIMAL TOXINS

  2. PLANT TOXINS RICIN Small protein, 2 polypeptides (short A chain, larger B chain) linked by disulphide bridge B chain links ricin to outside of cell via galactose in a glycoprotein Ricin internalized, released from glycoprotein and chains separate at disulphide bridge B chain makes hole in vacuole wall, A chain enters cytoplasm, targets ribosomes

  3. RICIN β chain  chain Binds to galactose Endocytosis Cell wall RNA Cell death

  4. BRACKEN Toxic agent – ptaquiloside Becomes carcinogenic when ingested Ptaquiloside molecule opens up, free end attaches to N atom in DNA base adenosine, breaks DNA Japan – bracken shoots frequently eaten, may be linked to high incidences of throat cancer Animals eating bracken – bladder/intestinal cancers Risk of toxins passing into food chains via cows’ milk

  5. FLUOROACETATE Found in numerous plants from S. America, S. Africa, Australia May have evolved as defence against herbivores Commercially known as 1080, used in N. Zealand & Australia to kill mammalian pests Blocks Kreb’s cycle in mitochondria by binding to enzyme aconitase

  6. PRODUCTS REACTANTS Glucose Energy Pyruvic acid CO2 Kreb’s cycle Energy Hydrogen Oxygen Water

  7. ALGAL BLOOMS Gambierdiscus toxicus Ciguatoxin Dinophysis sp. Okadaic acid Alexandrium Saxitoxin Gymnodinium breve Brevetoxin Pseudonitzschia

  8. Under optimal conditions, cells divide exponentially. 6-8000 cells possible in one week. Nutrients decrease, growth stops, gametes formed. 2 gametes join to form 1 cell, develops into zygote then into cyst Warm temp., increased light stimulate germination. Swimming cell emerges. Reproduces by simple division. Dormant, resting cyst in sediment. Can remain viable for considerable time

  9. Pseudonitzschia Amnesiac shellfish poisoning (ASP) Toxin – Domoic acid 1st reported from Canada Poisoning results in gastroentertis, some neurological effects possible in humans Acts as excitatory neurotransmitter Binds to sites in CNS, can cause lesions in brain UK scallop industry has been affected

  10. Gambierdiscus toxicus Ciguatera Fish Poisoning (CFP) Most commonly reported marine toxin Associated with consumption of contaminated reef fish, e.g. barracuda, snapper, grouper 2 Toxins: Ciguatoxin: lipid soluble. Neurotoxin, opens Na channels in cell membranes Maitotoxin: water soluble. Increases Ca influx through membranes

  11. Dinophysis sp. Diarrhetic Shellfish Poisoning (DSP) Toxin: okadoic acid Common in Europe, particularly Scandinavia & The Netherlands Okadoic acid – lipophilic, contracts smooth muscle in arteries, inhibits cellular activity by binding to enzymes

  12. Gymnodinium breve Neurotoxic Shellfish Poisoning (NSP) Toxin: brevetoxins, produces ‘red tide’ Common in Florida, Caribbean Brevetoxins: neurotoxic, open Na channels in membranes. Immunotoxic, inhibit enzyme activities in immune cells Not easily detectable or removable from food Fragile dinoflagellate, easily broken up in water, thus releasing toxin as an aerosol

  13. Alexandrium spp. Paralytic Shellfish Poisoning (PSP) Toxin – saxitoxin (21 forms) Significant problem on E. & W. coasts U.S.A., especially Alaska. Also recorded W. Europe. Saxitoxin – neurotoxin, binds to receptor on exterior of nerve cell membrane. Prevents Na movement through adjacent Na channel. Causes numbness, paralysis, disorientation. Toxicity ca. 1000x greater than cyanide, no antidote Toxicity changes considerably inside bivalve shellfish, most bivalves insensitive to saxitoxin

  14. OSO3 H

  15. 6x INCREASE in toxicity ACID HYDROLYSIS SO3 separated from 21

  16. FACTORS DETERMINING SAXITOXIN CONCENTRATIONS IN SHELLFISH • Amount of Alexandrium in water – bloom sizes variable • Toxin content of each Alexandrium cell • Feeding rate of shellfish • Transformation of toxin • TOXICITY TO MARINE MAMMALS: • High affinity binding to brain • May cause lack of control in thermoregulatory mechanisms • Disorientation increases difficulty in returning to surface following dives • During dives, blood channelled to heart & brain

  17. ANIMAL TOXINS

  18. BOX JELLYFISH Shallow waters, N. Australia Spawn at river mouths in late summer Migration in following spring Cardiotoxic, stings can also lead to skin necrosis Stings produced from nematocysts on the tentacles

  19. TETRODOTOXIN (TTX) Most associated with pufferfish (order Tetraodontiformes) Also found in large number of other fish and invertebrates

  20. PUFFERFISH Delicacy in Japan Symptoms: Numbness/tingling in lips Paralysis Usually fatal within 6-8 hours BLUE-RINGED OCTOPUS Australia/Indo-Pacific TTX contained in salivery glands

  21. Tetrodotoxin (TTX) Contains positively charged Guanidinium group and a Pyrimidinering Neurotoxin, blocks Na channels in membranes • May have bacterial origin: • Pufferfish grown in culture do not produce TTX until fed tissues from a toxin-producing fish • Blue-ringed octopus contains TTX-producing bacteria

  22. CONE SHELL Cone shells found on coral reefs worldwide Slow moving gastropods, detect prey by chemoreceptors on siphon Venom (mix of ca. 30 conotoxins) injected via proboscis, prey paralysed within 1-2 seconds Conotoxins - neurotoxins, some inhibitory, some exitatory Omega conotoxin: of interest to pain specialists, because it inhibits ion channels on nerve cells transmitting pain impulses

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