ScienceDaily (Aug. 22, 2012) — Enzymes involved in breaking down fat
can now be manipulated to work three times harder by turning on a
molecular switch recently observed by chemists at the University of
Copenhagen. Being able to control this chemical on/off button could
have massive implications for curing diseases related to obesity in-
cluding diabetes, cardio vascular disease, stroke and even skin
problems like acne. But the implications may be wider.
Possibly the most important discovery in enzymology
The results suggest that the switch may be a common characteristic
of many more enzymes. Since enzymes are miniscule worker-molecules
that control a vast variety of functions in cells, if the switches
are standard, it may well be one of the most important discoveries
in enzymology.
"If many enzymes turn out to be switched on in the same way as the
ones we've studied, this opens a door to understanding- and maybe
curing, a wide range of diseases," says professor Dimitrios Stamou.
Stamou heads a multidisciplinary team of scientists at the Nanoscience Center
and Department of Chemistry at the University of Copenhagen who published their
discovery in the scientific journal Journal of the American Chemical Society.
Switch contradicts previous understanding
The discovery of the enzymatic ignition key contradicts previous ideas of how
cells control the function of enzymes such as the fat eating lipase used in the
current study.
Researchers used to think that these enzymes work continuously at varying
levels of efficiency. But in fact they are quite lazy. Very much like construc-
tion workers they work at a fixed efficiency for a given amount of time (working
hours), and then they rest. And that's good news for enzyme designers.
Tripping their newfound switch resulted in tripling the working hours of
lipase enzymes, from 15 percent of the time to 45 percent by the Copenhagen
team.
Function follows form
In enzymes, function is decided by the shape of the molecule. So making them
more efficient would have required a major reconstruction. In some cases so
difficult that it is on the order of transforming a handsaw into a chainsaw,
says the chemist, Assistant Professor Nikos Hatzakis, who was deeply involved
in the scrutiny of the enzymes.
"Changing the fundamental shape of a tool is always difficult. Whether it's
saw or an enzyme. But working longer hours with the same tool is infinitely
easier. What we've achieved, is to make enzymes work longer hours" explains
Hatzakis.
Scrutiny on the Nanoscale
Observing that enzymes even have an on-off switch may sound easy, but first
the Bio Nano- team had to devise a way to study individual enzyme molecules.
These are so small, that there are trillions in just a drop of water. So measur-
ing the work of only one enzyme could be compared to looking down from the moon
to detect each time a carpenter in a building in Copenhagen swings his hammer.
Light-emitting fat
To perform their studies the researchers chose a fat degrading lipase enzyme
model system in collaboration with Danish industrial enzyme producer Novozymes.
They used "fat" that would emit light each time the enzyme took a bite. This
way they could monitor each and every catalytic cycle or single movement of
work. To ensure realism the enzymes were placed on an artificial cell wall. An
"in vivo like membrane system," says Stamou.
"Natural enzymes live in cells. Looking at them in a non native environment,
would tell us as much as looking at a carpenter working in outer space wearing
a space suit would tell us about builders," explains Dimitrios Stamou and con-
cludes:
"Now that we have understood how to switch enzymes on and off we could use
this knowledge in the future both for curing diseases but also to design novel
enzymes for industrial applications."
The research was supported by the Danish Research Councils and the Lundbeck
foundation.
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