1. Charles Darwin may have suffered from chronic arsenic poisoning. After his vo
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1. Charles Darwin may have suffered from chronic arsenic poisoning. After his voyage on the Beagle, he exhibited characteristic symptoms of eczema, vertigo, headaches, gout, and nausea. Fowler's solution, a popular 19th century tonic, may have been taken by Darwin. This tonic contained 10 mg of arsenite per ml. Arsenite and organic arsenicals are toxic because they can interact with sulfhydryl compounds to form bidentate adducts. Two enzymes that could be targeted include pyruvate dehydrogenase and -ketoglutarate dehydrogenase. a) Show what components of these two enzyme complexes may be affected b) What likely happens to carbohydrate metabolism and respiration? 2 ptsExplanation / Answer
a) The enzyme PDH has three components E1 (pyruvate dehydrogenase), E2 (dihydrolipoyl transacetolase) and E3 (dihydrolipoyl dehyrogenase). Arsenic is a strong inhibitor of E2 component as it forms an adduct with this component; this prevent this E2 component of the enzyme complex to regenerate inhibiting the enzyme.
alpha-ketoglutaraldehyde dehydrogenase is also a multisubunit enzyme with three components :1) -ketoglutarate dehydrogenase (E1), 2) Dihydrolipoyl succinyltransferase (E2), and 3) Dihydrolipoyl dehydrogenase (E3). Arsenite forms an adduct with E3.
b) The carbohydrate metabolism is inhibited as inhibition of PDH results in accumulation of pyruvate which acts a negative regulator for glycolysis and finally inhibits it. In addition inhibition of alpha ketogluaraldehyde, leads to decreased NADPH or FADH production which slows the ETC reducing production of ATP. The accumulation of TCA intermmediates also inhibit glycolysis. Thus the inhibition of these two enzymes reduces carbohydrate metabolism, severly decreasing body's ATP levels.
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