Glyoxylate cycle

The glyoxylate cycle is a metabolic pathway occurring in plants, certain vertebrates, and several microorganisms, such as E. coli and yeast.

The glyoxylate cycle allows these organisms to use fats for the synthesis of carbohydrates. This sequence of enzyme-catalyzed chemical conversions is absent in most vertebrates, including humans.

The relationship between citric acid and glyoxylate cycles and gluconeogenesis

Fatty acids from lipids are commonly used as energy source by vertebrates via degradation by beta oxidation into acetate molecules. This acetate, bound to the active thiol group of coenzyme A, enters the "citric acid cycle" (TCA cycle) where it is fully oxidized to carbon dioxide. This pathway thus allows cells to obtain energy from fat. To utilize acetate from fat for biosynthesis of carbohydrates, the glyoxylate cycle, whose initial reactions are identical to the TCA cycle, is used.

Cell-wall containing organisms, such as plants, fungi, and bacteria, during growth require very large amount of carbohydrates for biosynthesis of complex structural polysaccharides, such as cellulose, glucans, and chitin. In these organisms, in the absence of available carbohydrates (for example, in certain microbial environments or during seed germination in plants), the glyoxylate cycle permits synthesis of glucose from lipids via acetate generated in fatty acid β-oxidation.

The glyoxylate cycle bypasses the steps in the citric acid cycle where carbon is lost in the form of CO₂. The two initial steps of glyoxylate cycle are identical to those in the citric acid cycle: "acetate → citrate → isocitrate". In the next step, catalyzed by the first glyoxylate cycle enzyme, isocitrate lyase, isocitrate undergoes cleavage into succinate and glyoxylate (the latter gives the cycle its name). Glyoxylate condenses with acetyl-CoA (a step catalyzed by malate synthase), yielding malate. Both malate and oxaloacetate can be converted into phosphoenolpyruvate, which is the substrate of phosphoenolpyruvate carboxykinase the first enzyme in gluconeogenesis. The net result of the glyoxylate cycle is therefore the production of glucose from fatty acids. Succinate generated in the first step can enter into the citric acid cycle to eventually form oxaloacetate.

In plants the glyoxylate cycle occurs in special peroxisomes which are called glyoxysomes. Vertebrates cannot perform this cycle because they lack its two key enzymes, isocitrate lyase and malate synthase.