Understanding a rare hemoglobin mutation

The researchers found in a 2010 study that replacing the histidine, which forms a strong hydrogen bond to oxygen, with leucine caused a dramatic decrease in oxygen affinity and an increase in carbon monoxide binding.

Dr Olson and Birukou realized back then that histidine played a key role in discriminating between oxygen and carbon monoxide in hemoglobin.

“When Emmanuel wrote to me about his discovery, I already ‘knew’ what was happening with respect to carbon monoxide binding,” Dr Olson said.

He said the normal hydrogen bond causes bound oxygen to stick more tightly to hemoglobin in the same way hydrogen bonds cause spilled soda to feel sticky.

“When you touch it, the sugar oxygens and hydrogens make hydrogen bonds with the polysaccharides on your finger,” Dr Olson said. “That stickiness helps hold onto oxygen. But leucine is more like an oil, like butane or hexane, and oxygen does not stick well inside hemoglobin. In contrast, bound carbon monoxide is more like methane or ethane and can’t form hydrogen bonds.”

Andres Benitez Cardenas, PhD, a researcher in Dr Olson’s lab, did the experiment in which he put carbon monoxide on the mutant alpha subunit of hemoglobin Kirklareli. The bound carbon monoxide slowed down oxidation of the protein and prevented loss of heme and precipitation.

“In effect, Andres did the ‘smoking experiment’ to show why the father’s hemoglobin didn’t denature and cause anemia,” Dr Olson said.

He noted that the effect caused by Kirklareli, though unusual, is not unique. Patients with hemoglobin Zurich also have an abnormal form of hemoglobin that more readily binds to carbon monoxide.