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Monday, March 12, 2007

How Cells Make Tryptophan, Phenyalanine, and Tyrosine

Most species have to synthesize all of their amino acids from simple compounds. Several of the metabolic pathways are quite complicated, especially those leading to the complex aromatic amino acids like tryptophan, phenyalanine, and tyrosine. Many animals, including humans, have lost the ability to make these aromatic amino acids. We assume that the loss was not lethal because it was easy to get adequate amounts in the diet. The fact that we can't make them means that tryptophan, phenylalanine, and tyrosine are essential amino acids.

The other essential amino acids also have complicated biosynthesis pathways. We have also lost the ability to synthesize lysine, methionine, threonine, valine, leucine, isoleucine, and histidine.

Let's look at the pathway for the synthesis of tryptophan, phenylalanine, and tyrosine as seen in bacteria, plants, fungi, and protists. These are species that cannot get adequate supplies of pre-formed amino acids so they have to make all of the amino acids needed for protein synthesis de novo.

The first part of the pathway begins with a simple three carbon compound (phosphoenolpyruvate) and a simple carbohydrate derivative (erythrose 4-phosphate). These are combined in a series of four reactions to produce shikimate, a common metabolite in bacteria and most eukaryotes. Shikimate is then phosphorylated by shikimate kinase to make shikimate 5-phosphate.

The next step is very important. A three carbon addition to shikimate yields the complicated product 5-enolpyruvylshikimate 3-phosphate. The addition to the ring will eventually become the core part of the amino acid. This reaction is catalyzed by the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase) an enzyme that we'll hear more about very soon.

The final step in the first part of the pathway is the removal of the phosphate group to produce chorismate. Chorismate is another common metabolite in all species except animals.

The three aromatic amino acids are all made from chorismate (see below). The pathway to tryptophan is complicated but those leading to phenylalanine and tyrosine are much simpler. In addition to the pathway shown, tyrosine can also be made directly from phenylalanine by hydroxylation, in a reaction catalyzed by phenylalanine hydroxylase. That's why tyrosine is sometimes not listed as an essential amino acid; it's not essential if there are adequate supplies of phenylalanine in the diet. (Defects in phenylalanine hydroxylase are responsible for phenylketonuria.)

The important point for later on is the chorismate pathway. It is absolutely crucial for life in most species but it isn't even present in most animals. Blocking that pathway with a herbicide in plants will be lethal but the herbicide will have no effect on animals.


  1. Can you please tell me why herbicides such as Roundup, which inhibit the enzyme involved in the synthesis of tyrosine, tryptophan and phenylalanine, do not have a similar effect in humans?

  2. From the 1st paragraph...

    "Many animals, including humans, have lost the ability to make these aromatic amino acids."

    So there is no pathway to block in animals, so the compound does not have this effect.