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Rensselaer Polytechnic - Pyruvate Dehydrogenase & Krebs Cycle
Advanced discussion. Don't panic. Good reading comprehension exercise.

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Special points of emphasis

Reactions of Carboxylic Acids and Derivatives

The Eukaryotic Cell

Bioenergetics and Cellular Respiration

The Digestive System and Nutrition

Read for comprehension. Although glycolysis takes place in the cytoplasm of eukaryotic cells, the oxidative decarboxylization of pyruvate to form acetyl CoA and, later, the citric acid cycle take place within the mitochondria. The oxidative decarboxylization of pyruvate is catalyzed by the pyruvate dehydrogenase complex and enables the net conversion of pyruvate, CoA, and NAD+ into acetyl CoA, CO2, and NADH. Pyruvate is an α-keto acid, so its decarboxylization, like that of α-ketoglutaric acid in that citric acid cycle, is more difficult mechanistically to achieve than the decarboxylization of Isocitrate, which in the citric acid cycle is oxidized to form a β-keto acid, which is easily decarboxylated. A key prosthetic group of the pyruvate dehydrogenase complex (and also of the α-ketoglutarate dehydrogenase complex) is TPP, which adds to the carbonyl group of pyruvate to form a tetrahedral addition compound suitable for decarboxylization. Deficiency of thiamine leads to deficiency of TPP and to the disease Beriberi.

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