lobin delivers oxygen and nitric oxide to tissues," said Stamler. According to the new data, however, the nematode hemoglobin uses nitric oxide to trigger an enzymatic reaction that actually consumes oxygen. These data suggest that the primary role of the nematode's hemoglobin is to destroy oxygen. This would make sense, Stamler explained, because the Ascaris parasite has a low tolerance for oxygen. "The worms can deal with oxygen, but they don't really like it," he said.

Even in low-oxygen environments such as the human intestine, where the worms live, oxygen molecules do seep in. These must be neutralized, which the worm's hemoglobin does by grabbing and consuming oxygen molecules in a unique enzymatic reaction driven by nitric oxide.

Using spectroscopic techniques, the scientists studied how the nematode hemoglobin acts in the presence of different concentrations of oxygen and hemoglobin. The results of these experiments led the researchers to propose that Ascaris destroys oxygen via a 10-step chemical reaction.

The key to this process, says Stamler, lies with the exact positioning of a single sulfur-containing amino acid within the oxygen-binding pocket of the nematode's hemoglobin. "If this amino acid is on one side of the pocket, the hemoglobin uses nitric oxide to destroy oxygen. If it's on the other side of the pocket, as it is in mammalian hemoglobin, nitric oxide acts as a regulator of oxygen delivery," explained Stamler.

The discovery places Ascaris hemoglobin at a unique evolutionary juncture between primitive hemoglobins that evolved in the first living creatures on the planet--when the Earth's atmosphere was composed mostly of nitric oxide--and modern hemoglobin found in mammals and birds.

"In the primordial atmosphere, nitric oxide came before oxygen," Stamler said. "It was probably there before any life form, and the first bacteria needed a way to protect themselves from nitric oxide." Nitric
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
30-Sep-1999

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