A compound in green tea that shows great potential for the development of drugs to treat two types of tumours and a deadly congenital disease has been revealed in a new study.
The research was led by Principal Investigator, Dr. Thomas Smith at The Donald Danforth Plant Science Center and his colleagues at The Children's Hospital of Philadelphia.
Glutamate dehydrogenase (GDH) is found in all living organisms and is responsible for the digestion of amino acids. In animals, a complex network of metabolites controls GDH.
For decades it was not clear why animals required such regulation but other kingdoms did not.
This was partially answered by the Stanley group's finding that a deadly congenital disease, hyperinsulinism/hyperammonemia (HHS), is caused by the loss of some of this regulation.
In this disorder, patients (typically children) respond to the consumption of protein by over secreting insulin, becoming severely hypoglycemic, often leading to death.
Using atomic structures to understand the differences between animals and plants, Dr. Smith and his colleagues discovered that two compounds found naturally in green tea are able to compensate for this genetic disorder by turning off GDH in isolated and when the green tea compounds were administered orally.
The Smith lab also used X-ray crystallography to determine the atomic structure of these green tea compounds bound to the enzyme. With this atomic information, they hope to be able to modify these natural compounds to design and develop better drugs.
Interestingly, two other research groups have validated and extended these findings to demonstrate that blocking GDH with green tea is very effective at killing two different kinds of tumours; glioblastomas, an aggressive type of brain tumour, and tuberous sclerosis complex disorder, a genetic disease that causes non-malignant tumours to grow on a number of organs.
The article, 'Green Tea Polyphenols Control Dysregulated Glutamate Dehydrogenase In Transgenic Mice By Hijacking The ADP Activation Site', has been published in The Journal of Biological Chemistry.