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PKU, Amino Acids, and Cancer-How Do They All Relate?


Written by: Mayukha Kashyap

Study uses phenylalanine as nanotherapy for cancer cells




Diet culture can be toxic. Some promote extreme protein while cutting out carbs and sugar, even though the body needs both to survive. Others promote low protein when protein is what helps build muscle mass. With such varying diets, it’s challenging to understand which ones are considered healthy or not. Specific diets may also help one body type more than another. However, sometimes diets are necessary for one to survive. For those suffering from Phenylketonuria (PKU), eating without following a strict diet can result in death. But why?


Amino acids are the building blocks for protein. There are 20 different amino acids found naturally, with some considered essential and others as nonessential. Essential amino acids are not present in the body and mus therefore be acquired through diet, while nonessential amino acids are found in the body and don’t need any additional diets. Amino acids such as Lysine, Methionine, and Phenylalanine are considered to be essential compared to non-essential amino acids such as Serine. Not having enough of an essential amino acid will halt the production of certain proteins, affecting bodily functions. Diseases such as PKU are caused by this condition.


PKU is an autosomal recessive disease, meaning it affects body cells and needs one copy of the recessive gene from a parent for the disease to occur. The gene that codes for the enzyme phenylalanine hydroxylase mutates and converts excess phenylalanine into phenylpyruvate. Normally, phenylalanine is converted into tyrosine, however, the mutation affects this bodily function. The mutations thus result in a buildup of phenylpyruvate in the urine and blood. If PKU does not get treated, one can suffer from mental disabilities and brain damage. Interestingly, infants who suffer from PKU appear normal at birth because the mother is able to break down phenylalanine during pregnancy. Doctors are able to diagnose PKU through a blood test that measures elevated phenylalanine levels. PKU is treated through a low protein diet that prevents phenylalanine from building up in the body. Those who get diagnosed early and follow the diet strictly will not suffer from any problems. The figure below illustrates how PKU works.




Phenylalanine is also an amino acid that cancer cells rely on for growth and development. Recent studies have shown that preventing cancer cells from “eating’ essential amino acids such as phenylalanine can reduce tumor growth. In other words, because the cancer cells are unable to acquire the amino acids that cause them to grow and develop, the cancer is unable to grow and develop as well. However, it was also discovered that going on a strict diet would not suit patients as they are already prone to malnutrition and sensitive foods due to chemotherapy. Therefore scientists have found a novel way to incorporate phenylalanine into the body while killing cancer cells at the same time.


Scientists at Nanyang Technological University, Singapore (NTU Singapore) took a silica nanoparticle and coated it with phenylalanine. They gave to mice and discovered that the cancer cells were able to self-destruct. Because the nanoparticle was coated with phenylalanine, cancer cells would try to “eat” it, without knowing that the nanoparticle would kill them. This approach is known as nanotherapy. Nanotherapies have been shown to be effective because they are able to trick cells into self destructing without any dietary restrictions for the body. Researchers are now looking to apply this specific nanotherapy to other cancers and areas in the body. The best part? If a person suffering from PKU was diagnosed with cancer, they would be able to take part in this nanotherapy; the phenylalanine will not kill them as it will be digested by cancer cells, which will eventually self destruct.


Sources

“Brent Cornell.” BioNinja,

Nanyang Technological University. "'Trojan horse' approach to kill cancer cells without using

drugs." ScienceDaily. ScienceDaily, 23 September 2020.

Zhuoran Wu, Hong Kit Lim, Shao Jie Tan, Archana Gautam, Han Wei Hou, Kee Woei Ng,

Nguan Soon Tan, Chor Yong Tay. Potent‐By‐Design: Amino Acids Mimicking Porous

Nanotherapeutics with Intrinsic Anticancer Targeting Properties. Small, 2020; 16 (34):

2003757 DOI: 10.1002/smll.202003757



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