Glyoxylate cycle

[2] The cycle is generally assumed to be absent in animals, with the exception of nematodes at the early stages of embryogenesis.

Cell-wall containing organisms, such as plants, fungi, and bacteria, require very large amounts of carbohydrates during growth for the 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 the synthesis of glucose from lipids via acetate generated in fatty acid β-oxidation.

The acetyl CoA can also react with glyoxylate to produce some NADPH from NADP+, which is used to drive energy synthesis in the form of ATP later in the electron transport chain.

The levels of the main enzymes of the glyoxylate cycle, ICL and MS, are greatly increased upon contact with a human host.

Mutants of a particular species of fungi that lacked ICL were also significantly less virulent in studies with mice compared to the wild type.

The exact link between these two observations is still being explored, but it can be concluded that the glyoxylate cycle is a significant factor in the pathogenesis of these microbes.

[6][7] Vertebrates were once thought to be unable to perform this cycle because there was no evidence of its two key enzymes, isocitrate lyase and malate synthase.

[8] [9] Specifically, some studies show evidence of components of the glyoxylate cycle existing in significant amounts in the liver tissue of chickens.

[17][18] The prospect of engineering various metabolic pathways into mammals which do not possess them is a topic of great interest for bio-engineers today.

This is primarily of interest for engineers in order to increase the production of wool in sheep, which is limited by the access to stores of glucose.

By introducing the pathway into sheep, the large stores of acetate in cells could be used in order to synthesize glucose through the cycle, allowing for increased production of wool.

[19] Mammals are incapable of executing the pathway due to the lack of two enzymes, isocitrate lyase and malate synthase, which are needed in order for the cycle to take place.

This illustrates that much more research needs to be done on the topic, and suggests it is possible that a high expression of the cycle in animals would not be tolerated by the chemistry of the cell.

Overview of the Glyoxylate Cycle