"In the beginning, oxygen was toxic to early plants and worms and even late bacteria," Stamler said. "Early hemoglobin would bind tightly to the oxygen and consume it, acting as a detoxifier. However, in man, hemoglobin is the molecule that carries oxygen. We know what the earliest hemoglobin did, and we know what it does now in man.
"The Ascaris hemoglobin, in the presence of NO, consumes oxygen, creating the hypoxic, or oxygen-free environment, which it needs to live," Stamler said. "By doing so, the Ascaris hemoglobin is really acting like a new enzyme, or a deoxygenase, using NO to detoxify the oxygen around it."
It appears that structural differences have evolved in the Ascaris and human hemoglobin molecules that account for their different capabilities. The actual location on the molecule where the chemical reactions take place differ in the two hemoglobins, but they both employ a residue called cysteine that enables hemoglobin to actively use NO.
"In the Ascaris hemoglobin, the cysteine carrying NO is at the front, next to the oxygen, which leads to deoxygenation; and in humans, it is located at the back, away from the oxygen," Stamler said. "Since the gases are carried on opposite sides of the molecule, they do not react with each other, allowing for the release of NO and transport of oxygen. The primordial function of detoxification has transformed into a respiratory function in man."
While it appears that Ascaris hemoglobin is primarily involved in the canceling out of oxygen, the Duke and Washington University research also points to another function -- protecting the worm from NO that is present in the host gut or produced by the host's immune system.
"This ability to metabolize NO is very similar to the hemoglobin of
early bacteria, but the As
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Contact: Richard Merritt
Merri@mc.duke.edu
919-684-4148
Duke University Medical Center
29-Sep-1999