General Microbiology - Schlegel, H. 1987

Main mechanisms of metabolism and energy transformation
Tricarboxylic acid cycle

The Tricarboxylic Acid Cycle (Fig. 7.7) serves to oxidize the two-carbon compound acetate to СО₂ with the release of hydrogen. With the participation of three dehydrogenases, hydrogen is transferred to NAD(P), and directly to a quinone under the action of succinate dehydrogenase. As a rule, Coenzymes pass hydrogen on to the Respiratory Chain.

First, catalyzed by citrate synthase, acetyl-CoA is added to oxaloacetate, yielding citrate and releasing coenzyme A. Although the citrate molecule possesses mirror Symmetry, it undergoes asymmetric Cleavage. Aconitate hydratase catalyzes the reversible interconversion of three tricarboxylic acids:

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Fig. 7.7. The tricarboxylic acid cycle. To highlight the asymmetric cleavage of citrate, carbon atoms derived from acetate are highlighted in red up to the 8th reaction. Succinate is the first compound with a symmetrical Structure. The Glyoxylate cycle is indicated by dashed lines. Participating Enzymes: 1 - citrate synthase; 2 and 3 - aconitate hydratase; 4 and 5 - isocitrate dehydrogenase; 6 - a-ketoglutarate dehydrogenase; 7 - succinate thiokinase; 8 - succinate dehydrogenase; 9 - fumarase; 10 - malate dehydrogenase; 11 - isocitrate lyase; 12 - malate synthase.

Isocitrate dehydrogenase catalyzes the reactions leading from isocitrate to 2-oxoglutarate. There is one NADP-dependent enzyme system and one NAD-dependent system. Oxalosuccinate apparently remains enzyme-bound. 2-Oxoglutarate dehydrogenase catalyzes a conversion analogous to the Pyruvate dehydrogenase reaction. In addition to the enzyme protein, it involves thiamine pyrophosphate, lipoate, coenzyme A, NAD, and Mg^{2 +}. Succinate can be released directly from succinyl-CoA by the action of a CoA acylase or via a reaction coupled with ADP phosphorylation:

Succinate dehydrogenase oxidizes succinate to fumarate and transfers electrons to ubiquinone and Fe³⁺-cytochrome b. Fumarase (fumarate hydratase) adds Water to fumarate; this Hydration is stereospecific and yields malate. Malate dehydrogenase dehydrogenates malate to oxaloacetate, thereby regenerating the acetate acceptor. All reactions are reversible except for The formation of succinyl-CoA.

Ultimately, The oxidation of acetate in the tricarboxylic acid cycle yields 2 molecules of СО₂ and 8 [H] (of which 6 [H] are at the pyridine nucleotide level and 2 [H] at the flavoprotein level). In addition, a high-energy compound molecule is formed.

The tricarboxylic acid cycle not only Functions in the terminal oxidation of Organic compounds but also provides biosynthetic pathways with various precursors, such as 2-oxoglutarate, oxaloacetate, and succinate. The absence of these acids would lead to a shortage of oxaloacetate, which serves as the acceptor for acetyl-CoA, thereby disrupting the cycle. Replenishing the losses of tricarboxylic acid cycle intermediates is the function of so-called anaplerotic reactions. The most important mechanism for supplying the cycle with C₄-dicarboxylic acids involves the carboxylation of pyruvate and phosphoenolpyruvate (C₃ + C₁→C₄). These reactions will be discussed in more detail later (Section 7.5).