ACVPM Toxicology Practice Exam

The most toxic inorganic form of arsenic is the trivalent state, arsenite. In this oxidation state, arsenic strongly binds to sulfhydryl (thiol) groups in many enzymes, disrupting critical functions of cellular metabolism. A key target is enzymes in energy production that rely on lipoic acid, such as the pyruvate dehydrogenase complex, leading to impaired ATP generation and cell injury. This high reactivity with thiols also means arsenite readily enters cells and causes widespread dysfunction. In contrast, the pentavalent form (arsenate) acts more like a phosphate mimic and disrupts energy metabolism to a lesser extent, with less affinity for thiol groups, so it is less acutely toxic. Organic arsenic compounds are typically far less toxic than inorganic forms because they do not interact as strongly with cellular thiols and are more readily excreted.