People born with inherited metabolic disorder have a defective gene that results in a critical enzyme deficiency. As there is no cure so far for this disorder, patients with inborn congenital metabolic disorders must adhere to a strict diet their entire life.
In patients with inborn congenital metabolic diseases, the body does not produce a vital enzyme which results in the accumulation of metabolites — substances that are, among other things, the building blocks of DNA and proteins. This kind of accumulation is toxic and can cause severe developmental and mental disorders.
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One such disease is phenylketonuria (PKU) — a common inborn metabolic disease in children, in which the metabolite phenylalanine accumulates. Children with PKU have to adhere to a strict diet free of phenylalanine for the rest of their lives, which is difficult as most food products contain phenylalanine. If they don’t follow a strict diet, then they may face severe debilitating developmental problems.
New research from Tel Aviv University has found hope for green tea and red wine treating this disease. This research is based on two previous studies. In the first study, phenylalanine was shown to be capable of self-assembly and of forming amyloid structures like those found in Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases. In the second study, other metabolites that accumulate in other inborn congenital metabolic diseases were also shown to undergo self-assembly processes and form toxic amyloid aggregates.
In this new study, researchers examined whether the molecules identified in past studies known to hinder the formation of amyloid aggregates could also help counteract the amyloid formation process of metabolites in metabolic diseases.
The new research focused on two aromatic polyphenolic compounds —EGCG and tannic acid (found in green tea and red wine) using test tubes and culture cell systems. The two substances were tested on three metabolites related to three inborn metabolic diseases — adenine, cumulative tyrosine and phenylalanine. The results showed that both tannic acid and EGCG were effective in blocking the formation of toxic amyloid structures. The researchers also used computer simulations to verify these mechanisms.
This study has great potential for understanding and treating a wide range of metabolic diseases, neurodegenerative diseases and even cancer whereby metabolites accumulation has a detrimental effect.
Source: Communications Chemistry
