Glyoxylate cycle

Of the glyoxylate cycle is a pathway that enables the synthesis of C4 - carbohydrates of two molecules of acetyl -CoA. In one complete cycle as a molecule is formed succinate. It is similar to the citric acid cycle and occurs in plants, fungi, many bacteria and some invertebrates but not in vertebrates and man. The pathway is also called cancer Kornberg cycle or Krebs- Kornberg Beevers cycle after its discoverers Hans Adolf Krebs, Hans Leo Kornberg and Harry Beevers.

Alternative metabolic pathways for assimilation of acetate are ethylmalonyl -CoA pathway and the Methylaspartatzyklus.

Biochemistry

As in the citric acid cycle of the glyoxylate cycle begins with the condensation of a molecule acetyl- CoA with oxaloacetate, which citrate is formed. This reaction is catalyzed by citrate synthase. The citrate is converted by a aconitase in isocitrate.

Two consecutive reactions the Decarboxylierungsschritte the citric acid cycle now be bypassed. Firstly, isocitrate lyase catalyzes a ( EC 4.1.3.1 ), the cleavage Isocitrates to succinate and glyoxylate. This is then condensed on the other by a malate synthase ( EC 2.3.3.9 ) with another molecule of acetyl -CoA to malate. Since the CoA thioester is hydrolyzed, this reaction is irreversible. The circle closes when the malate is oxidized to oxaloacetate by malate dehydrogenase a, while NADH is obtained.

The net reaction for the conversion of two molecules of acetyl - CoA to succinate is as follows:

Since the released succinate can be fed into the citric acid cycle, the glyoxylate cycle is an example of an anaplerotic reaction.

Regulation

In plants, a compartmentalization of the reaction takes place. The majority of the reaction is localized in peroxisomes specialized in the so-called glyoxysomes. However, the citrate formed is brought into the cytosol and there converted by a cytosolic aconitase into isocitrate. This is transported back to the Glyoxysom and where it enters the glyoxylate cycle. The succinate formed is finally transported into a mitochondrion and can be included in the citric acid cycle there.

In microorganisms, the citric acid cycle is not in separate cell compartments instead, but in the cytoplasm. As a result, overlap citrate and glyoxylate cycle and need to be regulated.

The conversion of citric acid cycle to the glyoxylate cycle includes a switching operation at the isocitrate dehydrogenase ( IDH, EC 1.1.1.42 in Escherichia coli ). This enzyme catalyzes the oxidative decarboxylation of the citric acid cycle isocitrate into α -ketoglutarate. Normally dominates the activity of isocitrate dehydrogenase, and therefore the sequence of reactions of the Krebs cycle. The result is the generation of ATP. When carbohydrate deficiency but should instead isocitrate split for the glyoxylate cycle and carbohydrates are built. For this case, the IDH has inactivated and isocitrate lyase (IL) to be stimulated.

This is done by phosphorylation of a serine residue in IDH, which is catalysed by a protein kinase. This was the first example of a interkonvertierbaren enzyme in E. coli in 1989.

This modification can be reversed by a phosphoprotein phosphatase, so that the IDH regained their activity. This phosphatase is stimulated at a low ATP levels and by the presence of intermediates of glycolysis and the citric acid cycle, while the IC - lyase is thereby inhibited allosterically

Biological Significance

The succinate formed is converted into oxaloacetate. This can be converted into phosphoenolpyruvate, which catalyzes a phosphoenolpyruvate carboxykinase. Phosphoenolpyruvate is built up in the course of gluconeogenesis to glucose. As a result, allows the micro-organisms growing with glyoxylate acetate and acetyl-CoA that has been generated or extracted from various organic compounds (alkanes, isoprenes, alcohols, polyhydroxyalkanoate, acetic acid, triglycerides).

In plants the seedling uses the pathway to generate energy, and in particular carbohydrates (e.g., sucrose) for cell growth of stored triglycerides ( storage fats). This uses the seedling special grease reservoirs, or oleosomes to hydrolyze the triglycerides into fatty acids and glycerol. Glycerol is converted to glyceraldehyde 3- phosphate, and may then be further metabolized. The fatty acids released into the Glyoxisome and be degraded during the course of the β - oxidation to acetyl -CoA. Acetyl -CoA then flows into the glyoxylate cycle. The succinate formed therein is finally converted in the course of gluconeogenesis into glucose and can then be further processed to sucrose. Alternatively, succinate may be used in the citric acid cycle for power generation, before the photosynthesis of the seedling begins. In plants of the glyoxylate cycle can also be used for indirect transfer lipids. Plants can transport lipids either as chemical energy or as building material. Through the glyoxylate cycle this brought in a portable, water-soluble form (sucrose) and then converted back into lipids at the destination will be.

Since humans ( and other vertebrates ) isocitrate lyase and malate synthase, the two enzymes are missing, this formed acetyl -CoA can build either fats or respire in the citric acid cycle. As a result, a person can generate no carbs at a starvation diet from its fat reserves and this must ( necessarily ) obtained from amino acids. Therefore, muscles are broken down in this form of diet.

Alternative to the glyoxylate cycle

Some microorganisms growing on acetate have no active isocitrate lyase or she is missing them. It has been shown, however, that they use alternative metabolic pathways, such as the ethylmalonyl CoA way This is for example the case for Rhodobacter sphaeroides, Methylobacterium extorquens and other representatives of non- sulfur purple bacteria and Alphaproteobacteria. In the linear pathway, two reaction steps are required for the conversion of glyoxylate to malate and acetyl -CoA.

In some halobacteria, for example in Haloarcula marismortui, operates the Methylaspartatzyklus. For the conversion of isocitrate to succinate nine reaction steps are needed. Here, the eponymous methylaspartate, an unusual, non-proteinogenic amino acid is formed.