7 - Intermediary Metabolism

Abstract

Publisher Summary This chapter focuses on intermediary metabolism. The mitochondrial environment is central to the process of intermediary metabolism. The glycolytic pathway converts glucose to pyruvate in the cytoplasm. Pyruvate is in equilibrium with lactate and is translocated across the inner mitochondrial membrane by a specific monocarboxylic carrier mechanism. Pyruvate has two principal intramitochondrial fates. The first involves oxidative decarboxylation and activation to acetyl-CoA; the second involves carboxylation to oxaloacetate. These two reaction products, acetyl-CoA and oxaloacetate, can condense to form citrate, a 6-carbon molecule; and citrate is decarboxylated in the tricarboxylic acid cycle, yielding carbon dioxide and reducing equivalents. The reducing equivalents are reoxidized by Complexes I and II of the respiratory chain. The hydrogen ion reacts with molecular oxygen to form water. The liberated thermic energy is trapped in the high-energy phosphate bond of adenosine triphosphate (ATP) by the coupling of oxidation to phosphorylation. Evidence suggests that some small fraction is converted to lactate. Numerous inborn metabolic errors interfere with the process of intermediary metabolism. The classic metabolic signature of a biochemical defect involving oxidative metabolism is the elevation of tissue pyruvate and lactate concentrations.