The Science of PKU

The chemical dance

All food is broken down and turned into something your body can use. This is done by certain chemicals called enzymes and cofactors:

• Phenylalanine (Phe), which is found in protein, is broken down by an enzyme called phenylalanine hydroxylase (PAH) and a cofactor called tetrahydrobiopterin (BH4)
• These two molecules work together to transform Phe into another molecule, tyrosine (Tyr), which the body needs

Without both BH4 and working PAH, this transformation cannot take place.

In people with PKU, the PAH enzyme is broken, and therefore, the body cannot turn Phe into Tyr. The Phe concentration then builds up inside the body in the bloodstream, eventually passing into the brain.

How a chemist might describe the dance

One PAH molecule combines with one Phe molecule to create what is known as an enzyme-substrate complex. This complex then comes into contact with a BH4 molecule, removing a part of the BH4 called a hydroxyl group and attaching it to the Phe. The Phe with the extra hydroxyl group is now a new molecule called tyrosine, or Tyr, which is released from the enzyme-substrate complex into the bloodstream. The Phe and the BH4 are used up in this process, but the PAH is not. If either the PAH or the BH4 is unavailable, this process does not work, and excess Phe is left over, which over time will build to neurotoxic levels.

In summary

In short, people with PKU can’t rid themselves of excess Phe because the PAH enzyme is broken and cannot break down Phe. This problem with the PAH enzyme allows too much Phe to build up in the body, which can eventually affect the brain. Because of this, individuals with PKU must control their diet by consuming only minimal amounts of dietary Phe in order to keep their blood Phe levels relatively low.