Glyoxylate cycle

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

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The glyoxylate cycle allows these organisms to use fats for the synthesis of carbohydrates, a task which most vertebrates, including humans, cannot perform.

Absence in Animals

When fatty acids are consumed by vertebrates they are degraded by beta oxidation into large quantities of Acetyl-CoA. This acetyl group, bound to the active thiol group of coenzyme A, enters the citric acid cycle where it is fully oxidized to carbon dioxide and subsequently exhaled. This pathway allows the animal cells to obtain energy from fat.

Many cells in the human body require direct supply of glucose, either for synthesis of polysaccharides or for energy production when stored glycogen is depleted. Gluconeogenesis is a pathway which enables the production of glucose from smaller molecules such as pyruvate, lactate and glycerol.

Pyruvate is the initial compound in gluconeogenesis. It is converted to oxaloacetate, which is in turn converted to phosphoenolpyruvate (PEP). Seven further reactions bring about the production of glucose. Oxaloacetate is also the initial and at the same time end product of the citric acid cycle. Since acetate groups can enter the citric acid cycle and eventually be converted to oxaloacetate (which can continue to produce glucose in gluconeogenesis), it may seem that the production of glucose from fatty acids is possible.

However, this does not happen in vertebrates. Acetyl groups which enter the citric acid cycle are, as mentioned above, fully oxidized to form carbon dioxide. The acetyl group is therefore lost and cannot be converted to oxaloacetate, and later on to glucose.

It should be noted that Glyoxylate pathway is predominant in microorganisms and germinating seeds.

Solution - the cycle

Several organisms, however, found a solution to this, in the form of the glyoxylate cycle, which avoids the steps in the citric acid cycle where carbon is lost in the form of CO₂. The two initial stages of this cycle are identical to those of the citric acid cycle: acetate → citrate → isocitrate. The next step, however, is different: instead of decarboxylation, isocitrate undergoes cleavage into succinate and glyoxylate (the latter gives the cycle its name). Succinate can be channeled directly into the citric acid cycle and eventually form oxaloacetate. Glyoxylate condenses with acetyl-CoA, yielding malate. Both malate and oxaloacetate can be converted into phosphoenolpyruvate and gluconeogenesis can be initiated. The net result of the glyoxylate cycle is therefore the production of glucose from fatty acids.

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