Many bacteria and plants are able to subsist on acetate or other compounds that yield acetyl CoA. They make use of a metabolic pathway absent in most other organisms that converts two-carbon acetyl units into four-carbon units (succinate) for energy production and biosyntheses. This reaction sequence, called the glyoxylate cycle, bypasses the two decarboxylation steps of the citric acid cycle. Another key 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, 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, isocitrate is cleaved by isocitrate lyase into succinate and glyoxylate. The subsequent steps regenerate oxaloacetate from glyoxylate. Acetyl CoA condenses with glyoxylate to form malate in a reaction catalyzed by malate synthase, which resembles citrate synthase. Finally, 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. Succinate, released midcycle, can be converted into carbohydrates by a combination of the citric acid cycle and gluconeogenesis. Thus, organisms with the glyoxylate cycle gain a metabolic versatility.

Bacteria and plants can synthesize acetyl CoA from acetate and CoA by an ATP-driven reaction that is catalyzed by acetyl CoA synthetase.

Pyrophosphate is then hydrolyzed to orthophosphate, and so the equivalents of two compounds having high phosphoryl transfer potential are consumed in the activation of acetate.