Acetyl CoA that enters the citric acid cycle has but one fate: oxidation to CO2 and H2O. Most organisms thus cannot convert acetyl CoA into glucose. 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.
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In plants and in some microorganisms, there is a metabolic pathway that allows the conversion of acetyl CoA generated from fats 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 in the citric acid cycle.
The glyoxylate cycle (Figure 17.23), 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
In plants, these reactions take place in organelles called glyoxysomes. This cycle is especially prominent in oil-