Study may unlock enzyme's role in various diseases

New research on enzymes that regulate human biology has uncovered characteristics that could identify predisposition to conditions such as heart disease and some types of cancer, scientists say.
Researcher Brad Pierce from The University of Texas at Arlington, led a team that examined an oxygen utilising iron enzyme called cysteine dioxygenase or CDO, which is found in high levels within heart, liver, and brain tissues.
Enzymes are proteins that act as catalysts to enable metabolic functions, but under some circumstances these oxygen-dependent enzymes can also produce highly toxic side products called reactive oxygen species or ROS.
For the first time, researchers found that mutations outside the CDO active site environment or "outer coordination sphere" have a profound influence on the release of ROS.

Excess ROS has been linked to numerous age-onset human disease states, researchers said.
"Most research in the past has focused on the active site inner coordination sphere of these enzymes, where the metal molecule is located," said Pierce.

"What we're finding is that it's really the second sphere that regulates the efficiency of the enzyme. In essence, these interactions hold everything together during catalysis. When this process breaks down, the enzyme ends up spitting out high levels of ROS and increasing the likelihood of disease," Pierce said.
Pierce believes the findings from the CDO enzyme could be applied to other oxygen-dependent enzymes, which make up about 20 per cent of the enzymes in the human body.

"In principle, these findings could be extended to better understand how other enzymes within the class generate ROS and potentially be used to screen for genetic dispositions for ROS-related diseases," he said.
The study was published in the American Chemical Society journal Biochemistry.