Problem 14
Danbury shakes. From 1850 until World War II, Danbury, Connecticut, was considered the "hat capital of the world? One popular product was the felted fur hat. In the process of manufacturing the hats, fur was soaked in mercury nitrate. Many of the workers displayed neurological problems, including tremors, which came to be known as the "Danbury shakes." Suggest a biochemical explanation for the workers' problems.
Problem 16
Crucial intermediates. Thioesters not only are important in the reaction catalyzed by the pyruvate dehydrogenase complex, but also are crucial for the generation of pyruvate itself. What is the thioester in glycolysis that helps to generate pyruvate?
Problem 17
Lactic acidosis. Patients in shock often suffer from lactic acidosis owing to a deficiency of \(\mathrm{O}_{2} . \sim 2\) (a) Why does a lack of \(\mathrm{O}_{2}\) lead to lactic acid accumulation? (b) One treatment for shock is to administer dichloroacetate (DCA), which inhibits the kinase associated with the pyruvate dehydrogenase complex. What is the biochemical rationale for this treatment?
Problem 19
Force feeding. Inhibitors of pyruvate dehydrogenase kinase have been proposed as potential treatments for type 2 diabetes, which is characterized by high blood levels of glucose due to insulin resistance (p. 323). Suggest a biochemical rationale for this proposal.
Problem 20
A potent inhibitor. Thiamine thiazolone pyrophosphate binds to pyruvate dehydrogenase about 20,000 times more strongly than thiamine pyrophosphate does, and it competitively inhibits the enzyme. Why?
