Mechanism of arsenic poisoning: The toxicity of arsenic is explained primarily by the inhibition of enzymes such as pyruvate dehydrogenase , which require lipoic acid as a coenzyme (see p. 110). However, pentavalent arsenic (arsenate) also can prevent net ATP and NADH production by glycolysis, without inhibiting the pathway itself. The poison does so by competing with inor- ganic phosphate as a substrate for glyceraldehyde 3-phosphate dehydrogenase , forming a complex that spontaneously hydrolyzes to form 3-phosphoglycerate (see Figure 8.18). By bypassing the synthesis of and phosphate transfer from 1,3- BPG, the cell is deprived of energy usually obtained from the gly- colytic pathway. [Note: Arsenic also replaces P i on the F 1 domain of ATP synthase (see p. 78), resulting in formation of ADP-arsen- ate that is rapidly hydrolyzed.]