The glyoxylate refers to the anaplerotic pathway of the TCA (tricarboxylic acid) cycle, which enables growth in organisms using C2 compounds and bypassing the steps that generate carbon dioxide in the TCA cycle. The two unique enzymes that are used in this route are malate synthase and isocitrate lyase and malate synthase (Dunn, Ramírez-Trujillo, & Hernández-Lucas, 2009). Another notable difference between the glyoxylate cycle and the TCA cycle is that the glyoxylate cycle uses two molecules of acetyl CoA enter in every turn as compared to one acetyl CoA molecule used in the citric acid cycle.
Just like the TCA cycle, the glyoxylate cycle starts with acetyl CoA condensation with oxaloacetate to produce citrate. The citrate is then isomerized to form isocitrate. Instead of decarboxylating the isocitrate as in the TCA cycle, isocitrate under does cleavage using isocitrate lyase to form succinate and glyoxylate. The steps that follow convert the glyoxylate to oxaloacetate. Acetyl CoA undergoes a condensation process with glyoxylate to produce malate in a reaction that is catalyzed by malate synthase. This process resembles that of the citrate synthase. The last step involves the oxidation of malate to form oxaloacetate, which is similar to the citric acid cycle (Berg, Tymoczko, & Stryer, 2002).
The products of the bypass may be used to generating glucose through gluconeogenesis process or other biosynthetic processes. The glyoxylate cycle accomplishes the task of synthesizing carbohydrates by converting acetyl-CoA to succinate. In most of the microorganisms, the cycle enables the cells to use simple carbon compounds as a source of carbon when other complex sources like glucose are not available. The pathway occurs in plants, protists, bacteria, and fungi (Lorenz & Fink, 2002).
In plants for instance, the pathway takes place in special peroxisomes that are known as glyoxysomes. The cycle enables seeds to utilize lipids as a source of energy in the formation of the shoot when they are germinating. The seeds are not in a position to produce biomass through photosynthesis since the organs that are involved in the exercise are not available in the seed. The lipid store in the seed can thus be used in carbohydrate formations that are necessary in fueling both the growth and organism development.
The glyoxylate pathway is also able to give plants another way to diversify their metabolic processes. The process allows the plants to use acetate as a carbon source as well as a source of energy. The acetate molecule is then converted to acetyl CoA in a similar way as in the TCA cycle, which then moves into the glyoxylate cycle. The process releases succinate molecules, which can then be changed to form a number of carbohydrates using a combination of various metabolic processes. This enables the plant to synthesize molecules starting with acetate as the only source for carbon.
There are a number of pathways that have been engineered with an aim of introducing the pathways into mammals that lack the pathways. The glyoxylate cycle is among the pathways that engineers have tried to manipulate to see whether it can work in mammalian cells. The attempt has been done with an aim of increasing wool production in sheep, which is limited by lack of enough store of glucose. By introducing the glyoxylate pathway in sheep, the large store of acetate in the cells may be in the production of glucose, which is then used in wool production (Ward, 2000). Mammals have no capacity for executing the pathway since the two main enzymes used in the pathway, malate synthase and isocitrate lyase, are not available. It is, however, believed that the genes for the enzymes are generally not absent but have been turned off.
There are two main reasons why fungi use the glyoxylate cycle. The first reason is to enable them use simple carbon molecules when the complex molecules such as glucose and lactose are not available. The cycle allows the use of C2 compounds in the production of glucose through gluconeogenesis. The glucose produced may then be converted either into amino acids, RNA or into DNA. The pathway also enables the replenishing of the TCA intermediates using the C2 compounds.
The second reason why the fungi use the glyoxylate cycle lies on the importance of the cycle in pathogenesis. Studies show that glyoxylate cycle plays an important role in the virulence of phytopathogens. Through an insertional mutagenesis screen conducted for the avirulence in the Rhodococcus fascians, there was the identification of a mutant defective in the malate synthase. The Rhodococcus fascians is known to cause a gall in various plant species. Those strains that have the mutation may still be able to prevail on plant tissues without any symptoms but cannot cause disease to the plant. In the same way, an insertional mutagenesis screen conducted for avirulent mutants in the Leptosphaeria maculans, which is a fungal pathogen of canola, identified isocitrate lyase (Lorenz & Fink, 2002).
Reference List
Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Biochemistry (5th ed.). New York: W H Freeman.
Dunn, M. F., Ramírez-Trujillo, J. A., & Hernández-Lucas, I. (2009). Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis. Microbiology, 155(10), 3166-3175.
Lorenz, M., & Fink, G. (2002). Life and Death in a Macrophage: Role of the Glyoxylate Cycle in Virulence. Eukaryotic Cell, 1(5), 657–662.
Ward, K. (2000). Transgene-mediated modifications to animal biochemistry. Trends in Biotechnology, 18(3), 99–102.
