Plant and Animal Toxins Flashcards
what are the 2 types of RIPs and give examples
type1- single polypeptide chain. e.g. dianthin- in leaves of carnation
type2- 2 polypeptide chains, A the enzymatically active chain and B. e.g. abrin and ricin
what are RIPs?
an important group of plant toxins
ribosomal inhibitory proteins
where is ricin found ?
found in the seeds of ricinus communis
- these seeds are crushed to get castor oil
what are the sizes of the chains in ricin ?
a - 30kDa enzymatically active
b- 30kDa binding toxin to target cells
why are type 1 RIPs less potent than type 2 ?
type 1 only have an a chain therefore they dont have a guidance system so they cannot penetrate cells as easily
what is the most toxin plant poison ?
abrin
what is the most toxic non-peptide ?
palytoxin
- organic compound that targets sodium/potassium ATPase
what are more poisonous natural toxins or synthetic poisons ?
natural
what is the mechanism of action of ricin ?
1) BINDING TO SURFACE OF TARGET CELLS
- B chain binds to beta-1,4- galactose residues of glycoproteins/glycolipids - these are common parts of cell membranes so ricin can affect most cels
2) ENTERS BY ENDOCYTOSIS
- too large to cross by simple diffusion- it enters and is transferred to the early endosomes
3) TRANSPORT TO THE GOLGI COMPLEX
- on reaching early endosome most of the endocytosed toxin is either recycled back to cell membrane or goes via the late endosomes to the lysosome to be degraded. about 5% of endocytosed ricin is transported via vesicles to trans-golgi network
4) FROM GOLGI TO ER
- possible that ricin binds to a protein with a KDEL sequence and piggy backs its way to the ER- could be calreticulin
5) TRANSLOCATION FROM ER LUMEN TO CYTOSOL
- ricin undergoes reduction cleavage to release A chain. thought that A chain is treated as a mis folded protein and therefore is translocated out of the er using transport system for faulty proteins into cytosol for degradation
6) ACTION ON RIBOSOMES
- a chain released from ER acts on 60s ribosomal subunit to block protein synthesis - target is 28s rRNA- a chain splits the glycosidic bond between adenine and ribose at single but critical site - deadenylation may cause the loss of a binding site for the elongaion factors - preventing protein synthesis
what other function apart from prevent protein synthesis is ricin htought to cause ?
by DNA lyase - thought to chop DNA up within the cell
what are the 2 sugars present in the glycoproteins/lipids which ricin bind to ?
galactose and N-acetylglucosamine
how could ricin be used in cancer chemotherapy ?
target the toxin to specific cells to their target molecule
-produce an immunotoxin in which the B chain of ricin is replaced by antibody specific for either cell surface of tumour antigen or an antigen on the blood vessels of the tumour - this has worked in vitro and animal models
what is the worry about immunotoxins used in humans ?
drug may cause vascular leak syndrome characterised by widespread capillary leakage reducing cirulating volume of bloodm severe hypotension, hypoperfusion of organs and tissue oedema
why are the media and military interested in ricin ?
due to its potential as a chemical weapon
- likely it was used by bulgarain secret service to kill georgi markov in london 1978 - he was jabbed in the thigh by an agent carrying an umbrella and the tip had been modified to inject markovs skin with a small platinum capsule containing ricin- he died 2 days later
what are the 4 uses of ricin ?
cancer chemotherapy- immunotoxins, anti-viral agents, molecular neurosurgery= these have not been realised yet
bioterrorism
