pyr + NAD + CoASH <---> acetyl-CoA + NADH

     Pyruvate dehydrogenase contains a coenzyme, lipoic acid (green balls in figure), that helps complete the reaction, yet easily binds arsenic as AsO2, inhibiting the enzyme.  Less acetyl-CoA means less Krebs cycle, and thus less total ATP per glucose oxidized.

     Low levels of arsenic are used to kill molds on many crops; high doses can kill humans. Chronic arsenic poisoning causes sores on the skin, especially the feet. Arsenic can leak from the soil into drinking water wells; In India such contamination of water wells has exposed 75 millions people to toxic levels of arsenic.       next


Pyruvate Dehydrogenase 

lipomide
reductase
transacetylase

 

 

 

 

 

 

 


       In 2007 Courtney Kozul measured the baseline levels of arsenic in standard lab rodent chow (Purina LRD5001). It contained 360 ppb, 36 times more than the EPA allows for drinking water (which is 10 ppb - EPA regulates arsenic levels in water, but there are no limits for arsenic levels in food).
       Her concern was if one wants to study the effect of arsenic in drinking water at 10 ppb on animals systems, then all the data may be hidden by the effect of 360 ppb in feed. 
       Kozul decided to study the effect by comparing 360 ppb feed to a purified feed that contained less than 20 ppb arsenic. She analyzed a microarray analysis of 20,000 mouse genes in liver and lung of the two feed groups and found a 40-fold higher level of gene expression in the mice on the standard (high arsenic) diet, especially genes involved in xenobiotic (pathways that detoxify compounds as drugs and poisons) and glutathione metabolism (Chemico-Biologic-Interact, 173:129-140, 2008).
       Therefore, a standard rodent diet would hide the effects of increased arsenic in drinking water.