Unexpected role of enzyme may help develop anti-cancer drugs

A newly discovered role for the enzyme glutamine synthetase could have important implications for developing anti-cancer drugs according to a new UCL study. An intrinsic part of tumour growth is the sprouting of blood vessels, which supply cancerous tumours with the blood and energy that they need to survive. An international group of scientists led by Professor Peter Carmeliet at VIB in Belgium together with Professor Francesco Luigi Gervasio (UCL Chemistry and UCL Institute of Structural Molecular Biology) noticed an unusual connection between the enzyme glutamine synthetase, which was not previously known to be involved in regulating vascular development, and the growth of new blood vessels. Glutamine synthetase is known to catalyse the condensation of glutamate and ammonia to form glutamine and thus it plays an essential role in the nitrogen metabolism. The research, published in  Nature  and primarily funded by the EPSRC and the EU, could lead to the development of drugs that could restrict the growth of tumours by inhibiting the way in which the enzyme behaves. The team - including researchers at the American Cancer Society, Sun Yat-Sen University and the National Natural Science Foundation of China - used a combination of computational and experimental techniques. These revealed that the enzymes were "moonlighting" as facilitators for vascular sprouting, fixing a fatty acid to their surface, which then helps the enzyme move to the cell membrane where the vascular developmental activity takes place.