Shikimic acid pathway

The Shikimisäureweg or shikimate pathway is the name of a biochemical pathway, which occurs in plants and most microorganisms. It is of fundamental importance by the biosynthesis of the proteinogenic aromatic amino acids phenylalanine, tyrosine and tryptophan. In addition, it provides important raw materials for the plant secondary metabolism.

Reaction sequence

Main path

On the whole, the Shikimisäureweg runs in the various qualified safety organisms from similar but there are differences in detail. Therefore, it should be noted that the following reaction scheme relates to the well-studied relatively Shikimisäureweg the bacterium Escherichia coli.

As the start point of the Shikimisäureweges catalyzed by the enzyme 3- Desoxyarabinoheptulosanat -7 -phosphate synthase reaction of phosphoenolpyruvate (PEP) and erythrose - 4-phosphate is determined. This creates three - Desoxyarabinoheptulosanat -7 -phosphate, which is cyclized from the 3- dehydroquinate synthase, 3- dehydroquinate to the next step.

From 3- dehydroquinate caused by mediated by the enzyme 3- dehydroquinate dehydratase dehydration 3- dehydroshikimate, which is then reduced by the shikimate dehydrogenase to shikimate.

This is followed by the ATP-dependent phosphorylation of Shikimats by shikimate kinase to shikimate -3-phosphate. The reaction catalyzed by the 5- enolpyruvylshikimate-3 -phosphate synthase reaction with another molecule of phosphoenolpyruvate then gives 5 ​​- enolpyruvylshikimate-3 -phosphate.

After cleavage of the phosphate group by the chorismate synthase is from chorismate.

The chorismate mutase catalyzes a Claisen rearrangement of chorismate to prephenate conversion.

Branches of the pathway

The synthetic routes of the two amino acids tyrosine and phenylalanine share only at the prephenate. For the Tyrosinsynthese prephenate is converted by a prephenate into 4 -hydroxyphenylpyruvate. Phenylalaninzweig in the synthesis path, the prephenate dehydratase catalyzes the reaction of prephenate to phenylpyruvate. In a last Transaminierungsschritt arise from the two precursors, the respective amino acids tyrosine and phenylalanine. Alternatively, however, first be prephenate transamination to arogenate, which is then converted either by a Arogenatdehydratase in phenylalanine or a tyrosine in Arogenatdehydrogenase.

Already at the intermediate chorismate synthesis of the aromatic amino acid tryptophan branches off from the main path. In the first step, the anthranilate synthase converts chorismate into anthranilate, which reacts with phosphoribosyl pyrophosphate to Anthranilatphosphoribosyltransferase means of the N-( 5-phosphoribosyl ) - anthranilate. Catalyzed by the Phosphoribosylanthranilatisomerase Amadori rearrangement leads to 1 - (2- Carboxyphenylamino )-1- desoxyribulose - 5-phosphate. The indole -3- glycerolphosphate synthase produces the ring closure to indole-3- glycerolphosphate. The two last reaction steps, namely the elimination of glyceraldehyde -3-phosphate to the intermediate indole and its condensation with serine, tryptophan synthase catalyzes what provides tryptophan.

Biological Significance

Plants dominate the autotrophic beings the Shikimisäureweg, he is part of their primary metabolism, but also provides precursors for phytochemicals. Apart from the proteinogenic aromatic amino acids tryptophan, phenylalanine and tyrosine resulted in a wealth of other substances with aromatic rings ultimately from the shikimate pathway, the following list is by no means exhaustive and the shikimate pathway can also be combined with other synthetic routes:

  • Ubiquinones and plastoquinones
  • Vitamin E, vitamin K, folic acid
  • Siderophores
  • Lignin
  • Phenylpropanoids
  • Isoflavones, anthocyanins, lignans, stilbenoids
  • Cinnamic acid derivatives
  • Coumarin, vanillin
  • Benzoic acid ( salicylic acid, gallic acid, p- aminobenzoic acid )
  • Some alkaloids (morphine, colchicine)

But also in many bacteria, fungi, and protozoa of the Shikimisäureweg was detected. Contrast, animals lack the appropriate enzymes. Therefore, the amino acids phenylalanine and tryptophan are essential for them, tyrosine can be synthesized only directly from phenylalanine.

In addition to the Shikimisäureweg there are other possibilities for the biosynthesis of aromatic ring structures, such as the polyketide pathway and the nucleotide biosynthesis.

Others

  • The glyphosate compound used as a broad-spectrum herbicide in agriculture interrupts Shikimisäureweg by inhibiting the enzyme 5- enolpyruvylshikimate -3-phosphate synthase (EC 2.5.1.19 ).
  • Since many pathogens, the presence of Shikimisäureweges is common to the enzymes of this pathway are considered as a promising point of attack in the development of drugs with a very broad spectrum of activity, extending for bacterial, fungal and protozoal infections.
Gene Ontology Adenosine triphosphate Pathogenic bacteria
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