Coenzyme A in the spotlight again


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Titel Coenzyme A in the spotlight again
Looptijd 02 / 2011 - onbekend
Status Lopend
Onderzoeknummer OND1343364
Leverancier gegevens NWO

Samenvatting (EN)

Coenzyme A (CoA) is an essential cofactor, known for more than 60 years for its role in over 100 metabolic reactions. One canonical biosynthesis route has been identified in which CoA is synthesized starting from vitaminB5. In 2001 it was found by others that impaired CoA metabolism is associated with progressive loss of neuronal function, an association that is not understood. These results showed that, although CoA is known for decades, this cofactor is surrounded by ignorance. Several key questions that remain unanswered are; is CoA a determining factor in processes not directly related to metabolic pathways? What are the (other than metabolic) consequences of a cell, tissue or organism when CoA levels change? Is there an alternative route to synthesize CoA? In my research group a fruit fly model was developed in which we can modify and measure CoA levels in a highly sensitive way. With these developed tools and methods it was demonstrated that there exist an alternative route to synthesize CoA and we showed that altered CoA levels lead to specific consequences at the molecular, cellular and behavioral level. Moreover, my research showed that CoA is an influential factor in modifying protein acetylation, DNA damage responses, and neuronal functioning, strongly pointing to a role of CoA in non-metabolic processes. Here, this will be investigated further; the novel CoA biosynthesis route will be completely deciphered, the so far unknown functions and influences of CoA and its biosynthetic enzymes will be investigated. The gained knowledge will be at the base of a new research field and will have implications for CoA-related fields, ranging from brain diseases to the design of novel antibiotic drugs.

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Projectleider Prof.dr. O.C.M. Sibon

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