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Schematic of key mitochondrial metabolic pathways

Josephine S. Modica-Napolitano and Keshav K. Singh

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Figure 1. Schematic of key mitochondrial metabolic pathways. (a) Carbohydrate metabolism. Pyruvate produced from glycolysis undergoes oxidative decarboxylation to acetyl CoA, which is then oxidised in an eight-step process known as the tricarboxylic acid (TCA) cycle. The respiratory substrates NADH and FADH₂ generated through the TCA cycle are next oxidised in a process coupled to ATP synthesis. Electrons are transferred from NADH and FADH₂ to oxygen via enzyme complexes located on the inner mitochondrial membrane. Three of the electron carriers (complexes I, III and IV) are proton pumps, and couple the energy released by electron transfer to the translocation of protons from the matrix side to the external side of the inner mitochondrial membrane. Energy stored in the resulting proton gradient (i.e. the proton-motive force) is used to drive the synthesis of ATP via the mitochondrial enzyme ATP synthetase (complex V). (b) Fatty acid oxidation. Fatty acids undergo oxidative decarboxylation in the mitochondrial matrix to give acetyl CoA, which is fed into the TCA cycle, and new acyl CoA molecules that are successively shortened with each round of the cycle. Under certain conditions (e.g. fasting), acetyl CoA molecules are converted into ketones for use as an alternative energy source. (c) Urea cycle. Amino acid degradation resulting in excretion of nitrogen as urea occurs partly in the mitochondrion. The mitochondrion is also essential for several other processes (not shown), including gluconeogenesis, regulation of cytosolic NAD⁺, intracellular homeostasis of inorganic ions, and apoptosis (fig001ksb).

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