The "Danbury shakes" was a colloquial name for a series of neurological symptoms, including tremors, commonly exhibited by worke
rs in the hat manufacturing industry in Danbury, Connecticut. The symptoms were caused by the use of mercury nitrate to produce felt, a practice that was not banned in the United States until 1941. The administration of thiol‑containing reagents, such as dimercaprol, has long been used as a treatment to counteract mercury poisoning. What is the biochemical explanation for the symptoms of neurological dysfunction displayed by workers exposed to mercury nitrate?
a. The E1 component of pyruvate dehydrogenase complex is unable to form hydroxyethyl‑TPP, blocking the citric acid cycle in cells of the brain.
b. The dihydrolipoamide group of pyruvate dehydrogenase complex is inactivated, preventing the complete oxidation of glucose in the brain.
c. The inhibition of pyruvate dehydrogenase complex means NADH/NAD+ and ATP/ADP ratios are constantly elevated in the brain.
d. Gluconeogenesis is blocked due to pyruvate dehydrogenase complex inhibition, which starves neurological tissue of glucose.
Gluconeogenesis is blocked due to pyruvate dehydrogenase complex inhibition, which starves neurological tissue of glucose.
Explanation:
Metabolism is involved directly or indirectly in all processes conducted in living cells. The brain, popularly viewed as a neuronal–glial complex, gets most of its energy from the oxygen-dependent metabolism of glucose, and the mitochondrial pyruvate dehydrogenase complex (PDC) plays a key regulatory role during the oxidation of glucose. Pyruvate dehydrogenase kinase (also called PDC kinase or PDK) is a kinase that regulates glucose metabolism by switching off PDC. Four isoforms of PDKs with tissue specific activities have been identified. The metabolisms of neurons and glial cells, especially, those of astroglial cells, are interrelated, and these cells function in an integrated fashion. The energetic coupling between neuronal and astroglial cells is essential to meet the energy requirements of the brain in an efficient way. Accumulating evidence suggests that alterations in the PDKs and/or neuron-astroglia metabolic interactions are associated with the development of several neurological disorders. Here, the authors review the results of recent research efforts that have shed light on the functions of PDKs in the nervous system, particularly on neuron-glia metabolic interactions and neuro-metabolic disorders.
