Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
The Citric Acid Cycle
The citric acid cycle is not a linear, but a closed pathway

Now that we understand how acetyl-CoA is formed from Pyruvate, we are well-prepared to examine The Citric Acid Cycle. It is helpful to begin with a General Overview of the process. While Glycolysis proceeds via a linear sequence of enzymatic reactions, the enzyme system responsible for The Citric Acid cycle operates in a cyclic manner. As illustrated in Fig. 16-6, the cycle begins when acetyl-CoA transfers its acetyl group to the four-carbon compound oxaloacetate, yielding the six-carbon compound citrate. Citrate is then converted into isocitrate—another six-carbon intermediate—which undergoes dehydrogenation with the loss of CO2, thereby forming the five-carbon compound α-ketoglutarate. A second molecule of CO2 is subsequently cleaved from α-ketoglutarate, producing the four-carbon compound succinate. Through a series of three subsequent enzymatic reactions, succinate is converted back into the four-carbon oxaloacetate, where the cycle originated. Thus, each complete turn of the cycle results in the regeneration of oxaloacetate, which can then condense with a new molecule of acetyl-CoA to initiate another turn. In each turn, one two-carbon acetyl group (in the form of acetyl-CoA) enters the cycle, and two molecules of CO2 are released. Although one molecule of oxaloacetate is consumed to form citrate in each turn, this oxaloacetate is fully regenerated through the subsequent reactions. Consequently, oxaloacetate is not permanently consumed in the citric acid cycle; theoretically, a single molecule of oxaloacetate could catalyze The oxidation of an unlimited number of acetyl groups.

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Fig. 16-6. Outline of the citric acid cycle.

The number of carbon atoms in each intermediate is indicated within the red boxes. The four carbon atoms of succinyl-CoA reside in the succinyl moiety—that is, the portion of the molecule from which free succinate is formed.



Last update: 06/08/2026

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