The cycle is a modification of TCA cycle and discovered by Hans A. Krebs and H. L. Kornberg in 1957.

The glyoxylate cycle, a variation of the tricarboxylic acid cycle, is an anabolic pathway occurring in plants, bacteria, protists, and fungi. The glyoxylate cycle involves the conversion of acetyl-CoA to succinate for the synthesis of other  carbohydrates by plants.

The enzymes of the TCA cycle and the glyoxylate cycle are physically separated, with the glyoxylate cycle enzymes  are localized in a specialized organelle called the glyoxysome. The two additional enzymes that permit the glyoxylate shunt are isocitrate lyase and malate synthase, which convert isocitrate to succinate or to malate via glyoxylate.

In microorganisms, the glyoxylate cycle allows them to utilize Acetyl CoA as carbon source when complex sources such as glucose are not available. Microorganism convert acetyl-CoA into carbohydrates through glyoxylate cycle. The cycle is generally assumed to be absent in animals, with the exception of nematodes at the early stages of embryogenesis.

In higher plants and some microorganisms (bacteria, yeast and molds) the fats is converted into 2-carbon compounds (such as acetyl-CoA) and later into carbohydrates and later to other constituents through Krebs cycle. In higher plants the glyoxylate cycle operate  during germination of their seeds which contain large quantities of stored lipid and in microorganisms when they are grown on ethanol or acetate which function as the sole source of carbon in them.

The task (of converting fats into carbohydrates) in these organisms is, however, accomplished by means of a cyclic set of reactions called glyoxylate cycle or the latter nomenclature based on its two principal investigators.

The glyoxylate cycle utilizes five enzymes, of which two namely isocitrate lyase and malate synthase are absent in animals.

(a)          splitting of isocitrate into succinate and glyoxylate catalyse by isocitrate lyase and

(b)          conversion of glyoxylate into malate catalyse by malate synthase.

Thus, the glyoxylate cycle consists of 5 enzyme-catalyzed steps of which 3 steps are the same as in Krebs cycle, viz., Steps 1, 2 and 8.

The various steps are sequentially described as follows :

  1. Condensation of acetyl-CoA with oxaloacetate catalyzed by the enzyme, citrate synthase .
  2. Isomerization of citrate into isocitrate catalyzed by the enzyme aconitase .
  3. Cleavage of isocitrate into succinate and glyoxylate by the enzyme, isocitrate lyase ( = isocitrase or isocitratase). The enzyme is, thus, present at the branch point of two metabolic pathways (i.e., citric acid cycle and glyoxylate cycle) and appears to be susceptible to second-site control. Isocitrate lyase from Escherichia coli is, however, inhibited by phosphoenolpyruvate.
  4. Conversion of glyoxylate into malate by the enzyme, malate synthase.
  5. Dehydrogenation of malate to oxaloacetate by malate dehydrogenase.

There is a difference between the TCA and glyoxylate cycle. In the citric acid cycle the conversion of isocitrate to malate is an aerobic process, in glyoxylate cycle the conversion takes place anaerobically.

The overall reaction for the glyoxylate cycle may be written as :

The succinate formed in this reaction may be used for biosynthetic purposes. For example,

  1. Succinate can be converted to succinyl-CoA and used in the synthesis of porphyrins.
  2. Succinate can be oxidized to oxaloacetate  in via citric acid cycle. Oxaloacetate is utilized for the synthesis of aspartate and aspartate can be used for the synthesis of pyrimidines..
  3. Oxaloacetate can also be converted into phosphoenolpyruvate, which is then used for the reactions of gluconeogenesis.
  4. Finally, the oxaloacetate can also condense with acetyl-CoA and thus, initiate the reactions of the citric acid cycle.

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