Wednesday 1 August 2018

Green tea and red wine in metabolic illnesses

A recent study performed at the Tel Aviv University in Israel reveals that, over time, it is possible to treat congenital metabolic illnesses; the compounds used in the study were extracts from green tea and red wine.  

Most people with a congenital metabolic disease are born with a defective gene that results in a specific enzyme deficiency or an enzyme that is only limitedly effective. Because of this, certain substances are not or are insufficiently broken down, which leads to irreversible cell damage in cells that are susceptible to this. If effective treatment methods are not applied, currently the majority of patients have to follow a strict diet for their entire lives. 



The Israeli study published in Communications Chemistry, related to top journal Nature, reveals that certain compounds that occur naturally in green tea and red wine, block the formation of toxic substances. The researchers considered two compounds: epigallocatechin gallate (EGCG) found naturally in green tea and tannic acid found in red wine. The latter is known to prevent the formation of toxic amyloid structures that cause neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. In the case of congenital metabolic diseases, toxic waste products accumulate in the body in an uncontrolled manner. This can cause severe developmental and psychological disorders. 


A known example of a rare congenital metabolic illness is phenylketonuria (PKU). In patients suffering from PKU there is one amino acid (phenylalanine) that leads to problems. The liver of these patients is not capable of breaking down and processing the amino acid. This results in phenylalanine accumulating in the blood and in high concentrations in the brain. This impedes the growth and development of the central nervous system. If left untreated, PKU can also lead to dementia and serious behavioural problems. The defective or missing enzyme is phenylalanine hydroxylase, which usually breaks down phenylalanine in the liver. 
Infants with PKU must adhere to a strict diet free of phenylalanine for the rest of their lives. If they don’t, they may face severe developmental problems. Many foods contain this amino acid. Following a diet that is free from phenylalanine is therefore very difficult.


Amyloid structures

The new study is based on two previous studies performed at the Tel Aviv laboratory of Professor Gazit. The first study revealed that phenylalanine is capable of self-assembly and the formation of amyloid structures such as those seen in Alzheimer’s and Parkinson’s disease and other neurodegenerative disorders. In people with other enzyme defects related to congenital metabolic illnesses, the second study showed that other intermediate products also have these properties. Both studies led to new insights being gained in terms of awareness and understanding of this disorder. A clear overlap seems to exist between neurodegenerative disorders and congenital metabolic illnesses.  
The researchers performed an in vitro study. In other words, EGCG and tannic acid were investigated using test tubes and culture systems. The two substances were tested for three metabolic products which accumulate in variations of congenital metabolic illnesses: adenine, tyrosine and phenylalanine. The results were favourable, because both EGCG and tannic acid blocked the formation of toxic amyloid structures. The researchers also used computer simulations to verify the mechanism that sets in motion the formation of compounds. 



The results were found to be very valuable due to the new insights into the formation and accumulation of undesirable metabolic products. This is not only relevant for congenital metabolic diseases, but also for neurodegenerative disorders. The tools that have been developed are ground-breaking and have an enormous potential in terms of tackling a wide range of disorders in the future.