Methyl aspartate cycle

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The eponymous methyl aspartate

The Methylaspartatzyklus is a metabolic pathway of the synthesis of C 4 - carbohydrates (as succinate ) from two molecules of acetyl-CoA possible. So far it has been found in representatives of the halobacteria . Alternative metabolic pathways for the assimilation of acetate are the widely used glyoxylate cycle as well as the ethylmalonyl-CoA pathway .

The metabolic pathway owes its name to the intermediate product methyl aspartate.

Occurrence

The methyl aspartate cycle was originally detected in the halobacterium Haloarcula marismortui . Halobacteria are halophilic archaea that live in salt lakes under high salt concentrations of 3 to 5 molar and bright, microaerophilic and nutrient-rich conditions .

In the genome of a group of halo bacteria (strain I) genes were found for the cycle (such as Natrialba magadii ), while the other part largely relies on the glyoxylate cycle for Acetatassimilation. However, some genomes also contain genes for enzymes in both cycles, so that theoretically they can operate both.

biochemistry

The methyl aspartate cycle at a glance. Reducing agents were abbreviated with “2 [H]” (2 reducing equivalents ). The eponymous amino acid methyl aspartate was highlighted. The succinate formed in the cycle can re-enter the cycle via fumarate and oxaloacetate.

The methyl aspartate cycle begins with the condensation of acetyl CoA with oxaloacetate . This creates citrate , which is converted to α-ketoglutarate by enzymes of the citric acid cycle via isocitrate . A NADP -dependent glutamate dehydrogenase reacts with ammonium (NH 4 + ) to form L - glutamate , which converts a glutamate mutase ( EC 5.4.99.1 ) to the unusual amino acid methylaspartate .  

Methyl aspartate is deaminated to mesaconate by a methyl aspartate ammonium lyase ( EC  4.3.1.2 ) , which reacts to mesaconyl-CoA by a transferase . Succinyl-CoA is used as coenzyme A donor . Water condenses on mesaconyl-CoA, producing β-methylmalyl-CoA. This reaction catalyzes a mesaconyl-CoA hydratase. Finally, the intermediate is cleaved to glyoxylate and propionyl-CoA by the β-methylmalyl lyase.

Propionyl-CoA is first carboxylated with bicarbonate (HCO 3 - ), which catalyzes a biotin-dependent carboxylase . The reaction product is then converted to succinyl-CoA. After hydrolysis, succinate is formed from it. Glyoxylate reacts with another molecule of acetyl-CoA to form malate . This reaction is typical of the glyoxylate cycle and is catalyzed by malate synthase. After oxidation to oxaloacetate, the circle closes.

In the balance sheet, one molecule of succinate is formed from two molecules of acetyl-CoA.

Biological importance

Two metabolic pathways are known for the assimilation of acetate, the glyoxylate cycle and the linear ethylmalonyl-CoA pathway. Under aerobic conditions, some halobacteria use the glyoxylate cycle, such as Haloferax volcanii . Under strictly anaerobic conditions, halobacteria can produce pyruvate from acetyl-CoA. However, some aerobic halobacteria lack isocitrate lyase ( EC  4.1.3.1 ), a key enzyme of the glyoxylate cycle, as well as enzymes for the alternative ethylmalonyl-CoA pathway. However, they can grow on acetate by resorting to the methyl aspartate cycle to use acetate to build cellular matter.

The methyl aspartate cycle can become vital for the way of life of halobacteria in salt lakes. If there are short-term nutrient-rich conditions in the salt lake, these halobacteria create the storage substance polyhydroxyalkanoate . Under worse conditions, they then break down this storage substance into acetate-CoA, and use the acetate in the methylaspartate cycle. Alternatively, those archaea can obtain acetate from the breakdown of organic compounds such as fatty acids , alcohols or simple amino acids (e.g. L - lysine ).

High concentrations of glutamate are necessary to operate the cycle. This has actually been demonstrated in H. marismortui , while halobacteria that use the glyoxylate cycle have significantly lower levels of glutamate. Glutamate is an osmolyte , a precursor for γ-glutamylcysteine (an antioxidant ) and γ-polyglutamate . The latter is an extracellular polymer that the halobacteria use as a storage substance and as a protective cover against harsh environmental conditions.

The cycle couples nitrogen metabolism with acetate assimilation and forms the eponymous, non-proteinogenic amino acid methylaspartate as an intermediate. Nine reactions are necessary to turn isocitrate into succinate; in the glyoxylate cycle, it is comparatively only one reaction.

evolution

Genome analysis suggests that the genes for the methyl aspartate cycle may have passed through horizontal gene transfer from bacteria to halobacteria. In bacteria they initially served completely different metabolic tasks and in some halobacteria they were converted over time to acetate assimilation. With the involvement of other enzymes, a new way of assimilating acetate emerged. Presumably this adjustment was made as a result of the harsh environmental conditions with high nitrogen and salt content.

literature

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