These first hemoglobins were likely enzymes that consumed nitric oxide and had nothing to do with oxygen, Stamler noted. About 450 million years ago, as Earth's atmosphere began to contain more oxygen, mammalian hemoglobin evolved the ability to carry oxygen molecules to tissues and cart away the waste gas carbon dioxide.
In recent years, studies from a number of laboratories have identified a variety of roles for hemoglobin. Stamler, for example, has demonstrated that when hemoglobin binds to nitric oxide it causes blood vessels to dilate. But demonstrating that the nematode hemoglobin can function as an enzyme that catalyzes a series of chemical reactions is a first.
Moreover, the researchers' discovery of the worm's ability to use nitric oxide to kick start an enzymatic reaction helps explain the complicated interplay of hemoglobin and the three gases involved in respiration, oxygen, carbon dioxide and nitric oxide.
"The worm is evolving the first indications of a respiratory function involving oxygen concentrations," Stamler said. "The worm is controlling oxygen concentrations by using nitric oxide just as we do -- only with a different outcome. Instead of regulating its delivery to tissues, the worm's hemoglobin destroys unneeded oxygen."
Looking beyond the evolutionary implications of the findings, Stamler is excited by the prospect of using Ascaris hemoglobin as a molecular scaffolding upon which to design new therapeutic agents that can starve cancerous tumors of the oxygen they need to survive. "This is the first enzyme that eliminates oxygen," he said. "The hope is it could be used therapeutically," much like the so-called antiangiogenesis agents now being tested for their ability to shut off the blood supply to tumors.
Other authors of the Nature paper include Dena M. Minning of HHM
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
30-Sep-1999