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Illuminating stuff
August 1st, 2011
Fireflies are unprepossessing insects: stubby and brown, about a centimeter long, with a set of dark grey wings folded over their backs. However, their plain exterior belies their true talent: the little creatures herald the coming of summer by lighting up. This glowing magic is fueled by a much less romantic biochemical process: the breakdown of a molecule known as adenosine 5’-triphosphate, or ATP.
ATP’s breakdown into an intermediate form called ADP, or a final form, called AMP, is the basis of cellular energy – from the firefly’s light, to the movement of our muscles, electricity generation in nerves, and the building of proteins. At least 40 kilograms of ATP are used by the body at rest every day. The cost of purchasing this amount of pure ATP from a pharmaceutical company approaches $5million. During exercise, up to 0.5kg can be used every minute (around $62,000 worth!). Without ATP, life would not be possible.
Researchers in SVI’s Protein Chemistry and Metabolism Unit study how the body regulates its use of ATP, which is sensed via an enzyme called AMP-activated protein kinase. The group has recently published a paper in the prestigious journal Science, describing a new paradigm for the activation of AMPK, which could have implications for the treatment of diseases such as type 2 diabetes.
AMPK helps recharge the cell by stimulating the creation of more ATP. It controls the burning and storage of fats and sugars, and affects the level of sugars and cholesterol in the bloodstream. AMPK is of great interest in the fields of obesity, heart disease and diabetes because of its possible role in mediating the beneficial effects of diet and exercise.
For decades it was thought that only AMP, the final product of ATP breakdown, was capable of activating AMPK. SVI’s Dr Jon Oakhill, Professor Bruce Kemp and colleagues show for the first time that the intermediate energy breakdown product, ADP, can also trigger its activation.
Jon explains the finding, “We used to believe that the signal for our energy to recharge occurred only after the body had used up all its energy – the equivalent of finishing a marathon; in fact, we have shown that the process is activated much earlier, for example, after walking up a flight of stairs.”
Bruce says this study is important because it helps us to understand the mechanisms that lie behind the health benefits of exercise. “For 31 years it was thought that AMPK was only sensing levels of AMP. Our work shows that the activation of AMPK is much more sophisticated than anyone ever thought. Our ultimate aim is to develop drugs that can activate AMPK and mimic the effects of metabolic stress. This finding is an important step along the way to understanding this fascinating protein kinase.”
It turns out that understanding the biochemistry behind the little firefly’s light may not be so dull after all.