Plant and animal venom and toxin Flashcards
Mushroom toxins
Delayed onset(6 hrs or more after ingestion0
Amatoxin
Orellanine
Rapid onset(30mins to 3hrs)
Ibotenic acid, muscimol
Muscarine
Amanita phalloides
Most common and usually deadly source of mushroom poisoning
Amatoxins are thermostable bicylic octapeptides rapidly absorbed through intestine and INHIBIT PROTEIN SYNTHESIS
Tissue requiring high rate of protein synthesis affected most-GIT
Physiological response(4 STAGES) amatoxin
Latent phase(0-24hrs): no symptoms
Gastroenteritis: profuse diarrhea and vomiting(bloody), sever pain(6-24hrs)
Convalescence(24-72hr): looks like recovery
Fatal failure(4-9days): hepatic failure, encephalopathy, and renal failure
Amatoxin treatment
Charcoal: prevent further absorption via competitive inhibition of toxin uptake into cells, dialysis and liver transplantation
Silibin: supposed to be hepatoprotective-along with penicillin G(prevents toxin uptake by hepatocytes)
Alpha-amanitin effect
Non-specific transporters accumulate toxin into hepatocytes
Creates centrilobular necrosis-disrupting P450 synthesis = DAMAGE HEPATOCYTES
Filtered by glomerulus and reabsorbed by renal tubules
ATN-acute tubular necrosis
Affects GIT, liver and tubules most bc they require constantly synthesized protein
Bleeding factor disorder can occur bc clotting factors are not synthesized.
Cyclopeptides
Both amatoxins and phallotoxins are cyclopeptides
Phallotoxins: cyclic heptapeptides
Alpha-amanitin: appears to be the most active of the nine amatoxins identified
Thermostable bicyclic octapeptide
Most potent and specific inhibitor of mammalian RNA polymerase 2 known
Alpha-amanitin mechanism
Inhibits RNA polymerase 2 which prevents protein synthesis and causes cell death.
Via vinding the the bridge helix domain(between two largest polymerase subunits)-critical translocation
Far from the active site and this prevents nucleoside triphosphate entry-affinity is unaltered.
Alpha-amanitin inhibits bridge movement which prevents polymerase moving along DNA strand? Theory
Orellanine
Found in Cortinarius ssp mushrooms and grow in semi-mountainous region at the end of summer/fall
Cortinarius orrelanus-gentilis and speciosissimus cause most of the poisoning involving renal failure due to orellanine
TWO PHASE OF POISONING
1. Pre-renal phase: first few days=thirst,excessive urination,headache
Renal phase-several days after ingestion-oliguria to anuria
Orellanine mechanism
Toxic to the tubular epithelium
Interstitial nephritis with edema and infiltration of various blood cells
Irreversible kidney failure 50%, 15% die
Heat resistant
Leads to increased production of ortho semiquinone anion radicals and ROS along with decrease GSH
Coprinus ssp
Nature’s antabuse: inky caps and black fluid and are safe to eat as long as alcohol is NOT consumed
Metabolites or coprine inhibits aldehyde dehydrogenase irreversible
Heat stable, irreversible inhibitor
If alcohol consumed 72hrs of mushroom, classic antabuse effect-(headache, vomit, red face) due to build up of acetaldehyde
30-60mins post-ingestion
Full recovery is the norm
Muscarine
From Amanita muscaria mushrooms
Heat stable agonist at muscarinic acetylcholine receptors
Cholinergic syndrome-perspiration, salivation, lacrimation(PSL)
Hypotension, blurred vision, vomiting
Death from uncontrolled respiratory secretion-can’t exchange O2
Treated with atropine
Onset within 15min-1or2hrs
Animal venoms
Typically complex mixture of protein, polypeptides, lipids, amino acids, polysacchardies etc.
Three major source of experimental drug use:
Ligand-gated ion channels
Calcium channels
Phosphodiesterases
Black widow spiders
Not enough to kill human, found in all continent, 15X more potent than raddle
Bites painful and lead to numbness in affected area
Violent cramps, pain lower body, profuse sweating
Chills, fever, vomiting, difficulty breathing, partial paralysis
Hypertension and tachycardia
Death from CV and respiratory collapse
Antivenin(equine) available but must be administered quickly after bite occurs
Black widow venom
Contain 86 different proteins, including 7 latrotoxins-specific for prey
5 are insect-specific
1 is crustacean specific
1 is vertebrate specific-alpha latrotoxin(Alpha LTX)
Alpha LTX: induce massive NT release from presynaptic terminal
Action is sustained-possible reuptake block
Followed by morphological change and neuronal death
Alpha LTX Mechanism
Binds to synaptic terminal proteins-Neurexins(structural p that helps form synapse) and latrophilins(GPCR)
Latrophilins: evoke calcium-INDEPENDENT neurotransmitter release
Alpha LTX can also insert itself into artificial lipid bilayers, FORMS A CATION-selective channel->calcium influx can then cause NT release
VIA Tetramer structure
