QUESTIONS

1. Let's go back in time to your undergraduate days when you were studying - yes- GLYCOLYSIS.  Towards the end of glycolysis as we are heading toward the Krebs cycle, there is a reaction glyceraldehyde 3 -phosphate is converted to 1,3 DPG with an NADH & H+ coming off in the bargain. Then 1,3 DPG converts to 3-phosphoglycerate with the production of ATP.
   
   Aresenic screws this reaction up. How?
    
2. Which is more toxic?  Trivalent arsenates or pentavalent arsenates?
    
3. So what might be some clinical signs of arsenic poisoning?
    
4. Not that we're going to wait around for results but what would be the diagnostic specimen of choice?
    
5. What is BAL & how is it helpful?
   
   
   
   
    

ANSWERS

1. Well, it isn't arsenic per se; it's arsenATE (AsO4), a trivalently negative charged ion which closely resembles our organic phosphate friends.  The arsenate attacks our friends, attaches itself & before we know it, we've created 1-arseno-3 phosphoglycerate instead of 1,3 DPG. The newly formed arsenate is rapidly hydrolysed  & you get 3-phosphoglycerate.
   
   The problem is that  when you use arsenate instead of organic phosphate, you don't get any ATP when 3-phosphoglycerate is produced.  I hate when that happens.  I don't know about you but I need all the ATP that I can get.
   
   Note:  Arsenates act by interacting with the sulfhydryl groups of enzymes & coenzymes.  Glyceraldehyde 3-phosphate dehydrogenase (the enzyme of the above reaction) has an important cysteine goup at its active site.  I'll betcha this is where the arsenate is causing all the trouble (though I can't find this specifically in a book).
   
   
   
   
    
2. Trivalent arsenates are 4-10x more toxic than pentavalent.  Note carparsolate is trivalent.
   
   
   
   
    
3. Clinical signs of arsenic poisoning = intense abdominal pain, salivation, vomiting, diarrhea, staggering & rapid death.  Prognosis generally stinks.
   
   
   
   
    
4. The specimen of choice for arsenic levels is urine.  Liver & kidney are your next best bet.  Serum is useless because arsenate is quickly taken up by tissues.
   
   
   
   
    
5. BAL = British Anti-Lewisite (sounds like the member of some kind of political party).  It is also called Dimercaprol.  This is a sulfhydryl containing material that chelates arsenates.  It is no use except early in the course of the disease because the arsenates have been taken up by tissue.  BAL has toxic properties on its own but these   are usually self-limiting.  Chelation may lead to increased tissue arsenic release &  an exacerbation of signs.  BAL (plus the arsenic it picks up) is water soluble & the kidneys happily excrete it.