# Structural Biochemistry/Enzyme/Enzyme Phenylalanine Hydrozylase (PAH)
## What is Phenylketonuria (PKU)?

Phenylketonuria (PKU) is a genetic disorder in which the body cannot clear out the excess amount of amino acid phenylalanine (Phe). Individuals diagnosed with PKU lack the enzyme Phenylalanine hydroxylase (PAH), a protein used to break down Phe into another amino acid called tyrosine. This results in high levels of PAH in the human body, which is extremely toxic to the brain.

## Early Prevention/Treatment of PKU

Approximately 1 in 14,000 individuals are affected by PKU. During pregnancy, chorionic villus sampling can be done to screen the unborn baby for PKU. Furthermore, newborns can be tested for the disorder so that they can be treated early if they are diagnosed. Under laboratory analysis, a blood sample taken from a newborn can be tested and screened for PKU. This genetic disorder can be treated by controlling the levels of Phe in the body. Some treatments include certain restrictive diets. For example, people with PKU cannot eat foods that contain aspartame, an artificial sweetener. They can consume a new sugar-substitute called neotame which is similar to aspartame except that it combines the two amino acids differently. The effect is that it is 30 times as sweet as aspartame, so less is needed and thus less phenylalanine is produced when it is metabolized. People are advised to follow the diet throughout their lives. Moreover, foods such as milk and diet drinks contain large amounts of Phe. One who has PKU would be advised to avoid heavy intake of these foods. Another example would be to take supplements and vitamins to ensure a healthy balance of essential amino acids. Another possibility in treating PKU would be treating one with the enzyme PAL. This enzyme facilitates the disposal of excess Phe. Further clinical trials will determine if PAL is safe for human intake.

## Consequences of PKU

If medical actions and diet are not taken to prevent this condition, PKU can lead to mental retardation and neurological damage. Studies have shown that PKU affects the IQ of the affected individual and their ability to efficiently undergo neurological processes. Furthermore, studies have also shown that uncontrolled PKU affects cognitive functions such as processing speed, attention, inhibition, working memory, and motor control. Primarily for infants affected with PKU, discrepancy in working memory and inhibition are present. For children affected with PKU, discrepancy in working memory, inhibition, strategic processing, and response monitoring are present. For adults affected with PKU, insufficiency in working memory and attention are affected. Not only does a high level of Phe increase the neurological deficit in an individual, but it is also toxic to the human body.

## Further Treatment of PKU

For further controlled and treatment of PKU, children and adults should undergo timely cognitive, neurophysical, and social-emotional testings and evaluations. For infants and children up four-years old, annual evaluations should be taken. Children during their elementary school years should undergo evaluations under a psychologist to evaluate any metabolic disorders twice a year. For individuals in and beyond high school, psychological examinations should be taken to evaluate signs of decreased metabolic control or lack of social acceptance.

## References

BioMarin Pharmaceutical Inc. "Protecting the Brain: Testing and Treatment Approaches". PKU.com, 2009. Web. 29 Oct. 2011. <http://www.pku.com/Protecting-the-Brain/>
Meister, K. “Sugar Substitutes and Your Health.” Comprehensive Reviews in Food Science and Food Safety, 2006.