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PLA2
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by Parcelmouth on May 6, 2003
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This may seem a little bassackwards with my last question,but What exactly is phospholipase A2 and how does it work.What are it's effects and mechanisms of action? The more details the better.Also while I am on this subject if anyone knows of some good books or websites on the subject of snake venom components and toxicology please pass on the titles and authors.I have really gotten into this breakdown of the diffrent components of venom what they are and what they do.Also thanks to BGF great website alot of really excellent information and thanks for your response to my other question posted.Again thanks to everyone for yor responses.
J.S.
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RE: PLA2
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by BGF on May 6, 2003
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Hey mate
PLA2s = phospholipase enzymes that are in the PLA2 subgroup (based upon where biochemically, at which bond, they would cleave a phospholipid). There is PLA1, PLA2, PLB, PLC and PLD. The enzyme activity type is esterase activity.
In snakes, both the viper and elapids have PLA2s. However, they are not the same ones. There is some serious variation even just within the PLA2s. The ones from the pancrease (pancreatic-type) are different from those found in our joints (synovial-type).
When a snake lineage develops a new venom, the snake doesn't make something new. Instead it takes something else that has a useful mollecular scaffold, and then tweaks it. Thus, the snake venom prothrombin-activators are about 90% the same as the ones in the snakes blood (or ours for that matter) but the molecule binds thrombin with over 1000 fold more potency. So, all venom families have body equivalents.
The elapid snake venom PLA2s are of the pancreatic-type (i.e. that molecule was chosen as a venom molecule). The vipers by contrast chose the synovial-type PLA2 to modify. The fact that they are both PLA2s is just coincidence and underscores the importance of PLA2s within our own body (some types of arthritis involve disruption of the PLA2 cycle). They both took this rather active molecule, and gave it some drugs.
The toxic activities of the molecule are due to modifications on a different part of the molecule. i,e. the esterase activity might be due to a certain stretch of sequence in the middlish of the molecule. While if the non-moving part at the end of the molecule is changed in someway, it can kill.
The variety of activities of snake venom PLA2s is pretty dizzying. From killing all the flesh around the bitesite, to blowing up muscle cells, to binding to platelets to physcially targeting and destroying nerves. Pretty nasty class and are what give the taipans for example some of their real potency.
However, this is independent of the relationship of the two activities. Not many seem to make use of the esterase activity, for most its irrelevant.
Myotoxicity is perhaps one. All that are myotoxic also have a high level of phospholipase activity. However, not all that have high phospholipase activity also have myotoxic activity.
In contrast, the level of phospholipase activity is irrelevant but the more basic the molecule is (strongly basic is the key, the further past having a pI of 9.5, the stronger the antiplatelet activity).
The nerve acting ones are still not understood... depite the vast numbers of papers that have been published (what they hell have they been crapping on about then?!).
We have just disovered one (out of the Fea's viper actually) that instead of knocking the nerves off, we've discovered one that turns on a nerve in a way that no molecule (of any type) has ever done and causes it to continually fire in the most curious way.
Very very cool.
So, there's PLA2 101 ;-)
Cheers
B
Dean of SVVU (Snake Venom Virtual University)
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RE: PLA2
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by Rabies on May 6, 2003
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Hi J.S
If you've got the cash then I'd recommend"handbook of Clinical Toxicology of Animal Venoms and Poisons"by Jurg Meier&Julian White.Most probably the best book on the market for the lay person.
regards
John
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RE: PLA2
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by Rabies on May 6, 2003
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Hi,while on the subject of PLA2's,those that target the nervous system at the presynaptic membrane and any others that affect presynapticly ie dendrotoxins(which I think block sodium channels along the nerve membrane)Once they've attached them selves at the target area anti venom tends to have a minimal or no affect on these,why is that?and the damage they do is that reversible or can it lead to permanent damage?Hope you've got the time to answer.Thanks
regards
John
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RE: PLA2
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by BGF on May 6, 2003
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The neurotoxic PLA2s physically damage the presynaptic region of the nerve. Even after they leave, the damage is already done. In constrast, the various dendrotoxins (modified BPTI/kunitz-type protease inhibitors) as well as the presynaptically three finger toxin groups, bind to ion channels in the presynaptic side. They don't physically damage the nerve but just sit on the channel, usually blocking it but for some toxins on some channels, they keep the channel open. Once they pop off, thats it. Effects stopped.
Cheers
BGF
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