The glyoxylate cycle is a
metabolic pathwayoccurring in plants, certain vertebrates, and several microorganisms, such as E. coliand 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 oxidationinto 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 energyfrom 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 growthrequire 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 germinationin 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 succinateand glyoxylate(the latter gives the cycle its name). Glyoxylate condenses with acetyl-CoA (a step catalyzed by malate synthase), yielding malate. Both malateand oxaloacetatecan be converted into phosphoenolpyruvate, which is the substrate of phosphoenolpyruvate carboxykinasethe 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.
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