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Ricin - Wikipedia
A dose of purified ricin powder the size of a few grains of table salt can kill an adult human. Ricin is classified as a type 2 ribosome-inactivating protein RIP. Whereas type 1 RIPs are composed of a single protein chain that possesses catalytic activity, type 2 RIPs, also known as holotoxins, are composed of two different protein chains that form a heterodimeric complex.
Type 2 RIPs consist of an A chain that is functionally equivalent to a type 1 RIP, covalently connected by a single disulfide bond to a B chain that is catalytically inactive, but serves to mediate transport of the A-B protein complex from the cell surface, via vesicle carriers, to the lumen of the endoplasmic reticulum ER.
Both type 1 and type 2 RIPs are functionally active against ribosomes in vitro ; however, only type 2 RIPs display cytotoxicity due to the lectin -like properties of the B chain. In order to display its ribosome-inactivating function, the ricin disulfide bond must be reductively emergency 4 boston mod v2 er.
Ricin is synthesized in the endosperm of castor oil plant seeds. Within the lumen of the ER the propolypeptide is glycosylated and a protein disulfide isomerase catalyzes disulfide bond formation between cysteines and The propolypeptide is further glycosylated within the Golgi apparatus and transported to protein storage bodies.
The propolypeptide is cleaved within protein bodies by an endopeptidase to produce the mature ricin protein that is composed of a residue A chain and a residue B chain that are covalently linked by a single disulfide bond.
The quaternary structure of ricin is a globular, glycosylated heterodimer of approximately 60—65 kDa. While other plants contain the protein chains found in ricin, both protein chains must be present in order to produce toxic effects. For example, plants that contain only protein chain A, such as barleyare not toxic because without the link to protein chain B, protein chain A cannot enter the cell and do damage to ribosomes.
Ricin B chain binds complex carbohydrates on the surface of eukaryotic cells containing either terminal N-acetylgalactosamine or beta-1,4-linked galactose residues. In addition, the mannose -type glycans of ricin are able to bind to cells that express mannose receptors. The profuse binding of ricin to surface membranes allows internalization with all types of membrane invaginations.
The holotoxin can be taken up by clathrin -coated pits, as well as by clathrin-independent pathways including caveolae and macropinocytosis. The active acidification of endosomes is thought to have little effect on the functional properties of ricin. Because ricin is stable over a wide pH range, degradation in endosomes or lysosomes offers little or no protection against ricin.
This process is catalysed by the protein PDI protein disulphide isomerase that resides in the lumen of the ER. ERAD normally removes misfolded ER proteins to the cytosol for their destruction by cytosolic proteasomes.
Dislocation of RTA requires ER membrane-integral E3 ubiquitin ligase complexes,  but RTA avoids the ubiquitination that usually occurs with ERAD substrates because of its low content of lysine residues, which are the usual attachment sites for ubiquitin.
In the mammalian cell cytosol, RTA then undergoes triage by the cytosolic molecular chaperones Hsc70 and Hsp90 and their co-chaperones, as well as by one subunit RPT5 of the proteasome itself, that results in its folding to a catalytic conformation,   which de-purinates ribosomesthus halting protein synthesis. A single RTA molecule in the cytosol is capable of depurinating approximately ribosomes per minute. Within the active site of RTA, there exist several invariant amino acid residues involved in the depurination of ribosomal RNA.
In particular, Arg and Glu have been shown to be involved in the catalytic mechanism, and not substrate binding, with enzyme kinetic studies involving RTA mutants. The model proposed by Mozingo and Robertus,  based on X-ray structures, is joomla 2.5 templates with slideshow creator follows:.
Ricin is very toxic if inhaledinjectedor ingested. It can also be toxic if dust contacts the eyes or if it is absorbed through damaged skin.
It acts as a toxin by inhibiting protein synthesis. Ricin is resistant, but not impervious, emergency 4 boston mod v2 er digestion by peptidases. By ingestion, the pathology of ricin is largely restricted to the gastrointestinal tract, where it may cause mucosal injuries. With appropriate treatment, most patients will make a decent recovery. Because the symptoms are caused by failure to make protein, they may take anywhere from hours to days to appear, depending on the route of exposure and the dose.
When ingested, gastrointestinal symptoms can manifest within 6 hours; these symptoms do not always become apparent. Within 2 to 5 days of exposure to ricin, effects of ricin on the emergency 4 boston mod v2 er nervous systemadrenal glandskidneysand liver appear. Ingestion of ricin causes pain, inflammation, and hemorrhage in the mucous membranes of the gastrointestinal system.
Gastrointestinal symptoms quickly progress to severe nausea, vomiting, diarrhea, and difficulty swallowing dysphagia. Haemorrhage causes bloody feces melena and vomiting blood hematemesis. The low emergency 4 boston mod v2 er volume hypovolemia caused by gastrointestinal fluid loss can lead to organ failure in the pancreas, kidney, liver, and GI tract and progress to shock.
Shock and organ failure are indicated by disorientation, stupor, weakness, drowsiness, excessive thirst polydipsialow urine production oliguriaand bloody urine hematuria. Symptoms of ricin inhalation are different from those caused by ingestion. Early symptoms include a cough and fever. When skin or inhalation exposure occur, ricin can cause an allergy to develop. This is indicated by edema of the eyes and lips; asthma ; bronchial irritation; dry, sore throat; congestion; skin redness erythema ; skin blisters vesication ; wheezing ; itchy, watery eyes; chest tightness; and skin irritation.
An antidote has been developed by the UK military, although it emergency 4 boston mod v2 er not yet been tested on humans. Symptomatic and supportive treatments are available for ricin poisoning. Existing treatments emphasize minimizing the effects of the poison. Possible treatments include intravenous fluids or electrolytes, airway managementassisted ventilationor giving medications to remedy emergency 4 boston mod v2 er and low blood pressure.
If the ricin has been ingested recently, the stomach can be flushed by ingesting activated charcoal or by performing gastric lavage. Survivors often develop long-term organ damage. Ricin causes severe diarrhea and vomiting, and victims can die of circulatory shock or organ failure; inhaled ricin can cause fatal pulmonary edema or respiratory failure. Death typically occurs within 3—5 days of exposure. Vaccination is possible by injecting an inactive form of protein chain A.
In Bulgarian defector Vladimir Kostov survived a ricin attack similar to the one on Georgi Markovprobably due to his body's production of antibodies. When a ricin-laced pellet was removed from the small of his back it was found that some of the emergency 4 boston mod v2 er wax coating was still attached. For this reason only small amounts of ricin had leaked out of the pellet, producing some symptoms but allowing his body to develop immunity to further poisoning. The seeds of Ricinus communis are commonly crushed to extract castor oil.
As ricin is not oil-soluble, little is found in the extracted castor oil. Deaths from ingesting castor plant seeds are rare, partly because of their indigestible seed coatand because the body can, although only with difficulty, digest ricin. Most acute poisoning episodes in humans are the result of oral ingestion of castor beans, 5—20 of which could prove emergency 4 boston mod v2 er to an adult.
However, swallowing castor beans rarely proves to be fatal unless the bean is thoroughly chewed. The laboratory testing usually involves immunoassay or liquid chromatography-mass spectrometry. Although no approved therapeutics are currently based on ricin, it does have the potential to be used in the treatment of tumorsas a "magic bullet" to destroy targeted cells. The major problem with ricin is that its native internalization sequences are distributed throughout the protein.
If any of these native internalization sequences are present in a therapeutic agent, the drug will be internalized by, and kill, untargeted non-tumorous cells as well as targeted cancerous cells. Modifying ricin may sufficiently lessen the likelihood that the ricin component of these immunotoxins will cause the wrong cells to internalize it, while still retaining its cell-killing activity when it is internalized by the targeted cells.
However, bacterial toxins, such as diphtheria toxinwhich is used in denileukin diftitoxan FDA-approved treatment for leukemia and lymphoma, have proven to be more practical.
A promising approach for ricin is to use the non-toxic Emergency 4 boston mod v2 er subunit a lectin as a vehicle for delivering antigens into cells, thus greatly increasing their immunogenicity. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines. In the U. It is classified as an extremely hazardous substance in the United States as defined in Section of the U.
Ricin was emergency 4 boston mod v2 er the military symbol W or later WA. Army Chemical Mungaru male film dialogue itunes began a program to weaponize sarin.
The Soviet Union also possessed weaponized ricin. There were speculations that the KGB used it outside the Soviet bloc; however, this was never proven. The castor bean plant from which ricin emergency 4 boston mod v2 er derived is a common ornamental and can be grown at home without any special care.
Under both the Biological Weapons Convention emergency 4 boston mod v2 er the Chemical Weapons Conventionricin is listed as a schedule 1 controlled substance. Ricin is several orders of magnitude less toxic than botulinum or tetanus toxinbut the latter are harder to come by.
Compared to botulinum or anthrax as biological weapons or chemical nantu ghatak je kotha suina firefoxthe quantity of ricin required to achieve LD 50 over a large geographic area is significantly more than an agent such as anthrax tons of ricin vs.
A biopharmaceutical company called Soligenix, Inc. The vaccine is safe and immunogenic in mice, rabbits, and humans. It has completed two successful clinical trials. Ricin has been involved in a number of incidents.
Inthe Bulgarian dissident Georgi Markov was assassinated by Bulgarian secret police who surreptitiously shot him on a London street with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg. The prime suspects were the Bulgarian secret police: Georgi Markov had defected from Bulgaria some years previously and had subsequently written books and made radio broadcasts that were highly critical of the Bulgarian communist regime.
However, it was believed at the time that Bulgaria would not have been able to produce the pellet, and it was also believed that the KGB had supplied it. Earlier, Soviet dissident Aleksandr Solzhenitsyn also suffered but survived ricin-like symptoms after an encounter in with KGB agents. Ten days before the attack on Georgi Markov another Bulgarian defector, Vladimir Kostov, survived a similar attack.
Kostov was standing on an escalator of the Paris metro when he felt a sting in his lower back above the belt of his trousers. He developed a fever, but recovered. After Markov's death the wound on Kostov's back was examined and a ricin-laced pellet identical to the one used against Markov was removed. Several terrorists and terrorist groups have experimented with ricin and caused several incidents of the poisons being mailed to U.
A letter containing ricin was also alleged to pankhida garba s been sent to American President Barack Obama at the same time. An actress, Shannon Richardsonwas later charged with the crime, to which she pleaded guilty that December. Ricin has often been used as a plot device, such as in the television series Breaking Bad Season 2Season 4 and Season 5.
The popularity of Breaking Bad inspired several real-life criminal cases involving ricin or similar substances. Kuntal Patel from London attempted to poison her "controlling and selfish" mother with abrin after the latter interfered with her marriage plans.