Clinical Aspects

Arsenite and mercuric ions react with the —SH groups of lipoic acid and inhibit pyruvate dehydrogenase, as does a dietary deficiency of thiamin, allowing pyruvate to accumulate. Many alcoholics are thiamin-deficient (both because of a poor diet and also because alcohol inhibits thiamin absorption), and may develop potentially fatal pyruvic and lactic acidosis. Patients with inherited pyruvate dehydrogenase deficiency, which can be the result of defects in one or more of the components of the enzyme complex, also present with lactic acidosis, particularly after a glucose load. Because of the dependence of the brain on glucose as a fuel, these metabolic defects commonly cause neurologic disturbances.