What is Tryptophan Hydroxylase?

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  • Written By: Misty Knight-Rini
  • Edited By: Angela B.
  • Last Modified Date: 11 August 2019
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Tryptophan hydroxylase (TPH) is an enzyme that plays a role in the biosynthesis of serotonin. TPH is the catalyzing, or initial, step in the chemical reaction that turns tryptophan into serotonin. It is also the rate-limiting, or slowest, step of the reaction process. Tryptophan hydroxylase is a member of a family of amino acid hydroxylases that includes phenylalanine hydroxylase and tyrosine hydroxylase. These amino acid hydroxylases all play important roles in metabolic pathways, or chemical reactions that occur within cells.

Humans have two tryptophan hydroxylase genes, on the 11th and 12th chromosomes. TPH1, found on Chromosome 11, is expressed in tissues such as the skin and pineal gland that express serotonin. Tryptophan hydroxylase 1 is also expressed in the central nervous system. In contrast, TPH2 is only expressed in the central nervous system.

The inhibition of tryptophan hydroxylase in humans is closely linked to depression. Administering tryptophan stimulates serotonin production and serves as an antidepressant in humans and other mammals. Without tryptophan, the body cannot make serotonin. The human body does not produce tryptophan on its own but must, instead, obtain the amino acid from diet.


Experts disagree on the best way to get tryptophan into the body. Consuming foods with tryptophan does not always do the trick. For instance, turkey contains tryptophan, but eating turkey may actually lower the amount of tryptophan in the body. This is because tryptophan uses the same route to the brain as all other amino acids. Being the least plentiful of the amino acids present in the body, it has to fight with more common amino acids that typically beat it out.

Other researchers think eating protein and carbohydrates simultaneously allows tryptophan to reach the brain more easily. When carbohydrates are consumed, insulin is produced and most amino acids are directed toward the body’s muscles. Tryptophan remains untouched and is left to enter the brain.

The only guaranteed way to get tryptophan to the brain is by consuming it in the form of a dietary supplement. This can be difficult, though, because tryptophan supplements are banned in the U.S. The supplements are believed to have caused a wave of illness in the late 1980s and were banned as a result. Studies conducted on tryptophan supplements suggest they can greatly affect human behavior. A number of studies have shown positive effects in animals, and researchers are beginning to believe tryptophan has similar effects on humans.


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