Pyruvate dehydrogenase arsenite inhibition

Arsenite and mercuric ions react with the —SH groups of lipoic acid and inhibit pyruvate dehydrogenase, as... 

Petrick, J.S., Jagadish, B., Mash, E.A. and Aposhian, H.V. (2001) Monomethylarsonous acid (MMA(III)) and arsenite LD50 in hamsters and in vitro inhibition of pyruvate dehydrogenase. Chemical Research in Toxicology, 14(6), 651-56. 

Trivalent inorganic arsenicals, such as arsenite, readily react with sulfhydryl groups, such as GSH and cysteine (Scott et al, 1993 Delnomdedieu et al, 1994). The complex between arsenic and the vicinal sulfhydryl group is particularly strong. Arsenite inhibits pyruvate dehydrogenase (PDH) activity (Hu et al, 1998), perhaps by binding to the... 

Figure 17.20. Arsenite Poisoning. Arsenite inhibits the pyruvate dehydrogenase complex by inactivating the dihydrolipoamide component of the transacetylase. Some sulfhydryl reagents, such as 2,3-dimercaptoethanol, relieve the inhibition by forming a complex with the arsenite that can be excreted.

The enzyme pyruvate dehydrogenase can be inhibited by arsenite, which complexes with the reduced form oflipoic acid, thus making the lipoic acid unavailable for continued reactivity. This enzyme is also decreased in amount and activity during a thiamine deficiency (Fig. 11.10). 

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