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  Features 04/18/02

Dopey about dopamine: USU student researches brain chemistry

By Dylan Taylor

Dopamine and Norepinephrine.

When asked what he does for fun, Kyle Tubbs replied he enjoys snowboarding, wakeboarding, rock climbing and chemistry.


In fact, Tubbs, a 23-year-old student, can be found in the Eccles Science Learning Center at possibly any time, working on his college-funded undergraduate research.

"He's up there all night," said Lisa Berreau, faculty adviser over Tubbs' research.

However Tubbs, who has a dual major in psychology and chemistry, doesn't mind.

"I'm up there every day for about a couple of hours," said Tubbs of the chemistry lab that is practically his home.

So what is it that Tubbs finds more interesting than snowboarding and rock climbing? Well, it's all about copper.

Tubbs' university funded research deals with the construction of a model for a reaction involving a copper-based molecule found in a protein that participates in dopamine being synthesized into another chemical, norepinephrine.

"For about 30 years, there's been research involving the influence of dopamine in mood disorders, mostly depression," said Tubbs.

According to the Dictionary of Biological Psychology, dopamine is a chemical produced by the brain and found in neurons, or cells that make up the nervous system. Dopamine is involved in a variety of psychological processes including motor control, cognition and reward. Shortages of dopamine in the brain can give rise to Parkinson's disease, while fluctuations of dopamine have been associated, although not conclusively, with schizophrenia. Tubbs said the importance of this reaction lies in the fact that it is a necessary bodily function.

"It's a normal chemical reaction, something we all go through, that's how norepinephrine is synthesized," said Tubbs. "The chemical make-up of these neurotransmitters is so very important."

Norepinephrine, according to the Dictionary of Biological Psychology, is associated with attention, memory, regulation of sleep and fight-or-flight responses to stress. Norepinephrine is also known as noradrenaline and can be found in the brain, peripheral nervous system and kidneys.

"Big picture, if we understand how these different neurotransmitters are being synthesized in the body, maybe we can provide insight to chemistry involved in brain function as a whole," Berreau said.

Tubbs said,"Dopamine starts out and goes through a chemical reaction and becomes norepinephrine. During that chemical reaction there is an enzyme (protein catalyst). It's a copper center and it has some nitrogens and some sulfurs and it goes in and it actually participates in that transformation. What were trying to do is figure out what that metal is all about."

Tubbs said the main thing lacking in the literature associated with the subject is a comprehensive model of what happens during this chemical reaction.

"There are certain things people do know about it," Tubbs said.

Berreau described the simplified structure of the enzyme involves a copper center with one sulfur and three nitrogen atoms bonded to it.

Tubbs said the structure of these molecules is determined by a technique called X-ray crystallography.

"You try to grow a crystal of it (the molecule) and then you can look at that crystal and actually see what it looks like," Tubbs said.

However, the equipment used in X-ray crystallography is not available at Utah State University, so Tubbs has to send his crystals to another university. This copper molecule is part of a much larger protein that participates in the reaction.

"It's huge, thousands of atoms," said Berreau. "Its hard to understand with a protein this large what's going on with a single atom."

Berreau said that through these simplified models Tubbs is able to isolate the particular copper-based molecule and better understand it. While the structure and chemical make-up of the copper molecule is understood and the necessity of this molecule in the norepinephrine synthesis is also understood, what is not understood, Berreau said, is the actual step that involves the copper molecule in the transformation of dopamine into norepinephrine.

"We just want to understand that simple core reaction," said Berreau. "It's like seeing a building out in town and saying, 'I want to understand something about this building, I'm going to construct a model,'" said Berreau.

And on this scaled-down level, chemists like Tubbs are able to observe the more simplified reaction and use various chemical tools to measure it.

"We use simple structures that are related to the complex structure," said Berreau. And we're interested in it because it involves copper," said Berreau. "We are chemists interested in metals and how they function in biology."

Tubbs also views his research as an opportunity increase his knowledge in this field. As the primary researcher, Tubbs has been working on this project since August.

"It's kind of a starting point for me," said Tubbs.

Tubbs said he hopes his research will give him a good background for further meaningful research on how these chemicals interact in the brain with the environment to produce abnormal behavior.

Berreau agrees.

Berreau said through chemists like herself and Tubbs contributing fundamental knowledge on chemical structures of these dopamine reactions, they are contributing to the general understanding that could one day help in drug design. Berreau said their chemical understanding of the reaction gives people involved in drug design a basis to build arguments upon.

"We're the people trying to figure out the chemistry, down in the trenches," said Berreau.



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