Acetyl CoA that enters the citric acid cycle has only one fate: oxidation to CO₂ and H₂O. Most organisms thus cannot convert acetyl CoA into glucose, because, although oxaloacetate, a key precursor to glucose, is formed in the citric acid cycle, the two decarboxylations that take place before the regeneration of oxaloacetate preclude the net conversion of acetyl CoA into glucose.

In plants and some microorganisms, a metabolic pathway does indeed exist that allows the conversion of acetyl CoA generated from fat stores into glucose. This reaction sequence, called the glyoxylate cycle, is similar to the citric acid cycle but bypasses the two decarboxylation steps of the cycle. Another important difference is that two molecules of acetyl CoA enter per turn of the glyoxylate cycle, compared with one molecule in the citric acid cycle.

The glyoxylate cycle (Figure 19.10), like the citric acid cycle, begins with the condensation of acetyl CoA and oxaloacetate to form citrate, which is then isomerized to isocitrate. Instead of being decarboxylated, as in the citric acid cycle, isocitrate is cleaved by isocitrate lyase into succinate and glyoxylate. The ensuing steps regenerate oxaloacetate from glyoxylate. First, acetyl CoA condenses with glyoxylate to form malate in a reaction catalyzed by malate synthase, and then malate is oxidized to oxaloacetate, as in the citric acid cycle. The sum of these reactions is

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In plants, these reactions take place in organelles called glyoxysomes. This cycle is especially prominent in oil-rich seeds, such as those from sunflowers, cucumbers, and castor beans (Figure 19.11). Succinate, released midcycle, can be converted into carbohydrates by a combination of the citric acid cycle and gluconeogenesis. The carbohydrates power seedling growth until the plant can begin photosynthesis. Thus, organisms with the glyoxylate cycle gain metabolic versatility because they can use acetyl CoA as a precursor of glucose and other biomolecules.