What is breathing? The simple explanation is that animals, including humans, breathe in oxygen and exhale carbon dioxide. But a recent discovery has blown the lid off this paradigm by showing that respiration is not so simple.

In vertebrate animals, oxygen is breathed in through the lungs, bound to red blood cells and then transported through the blood to every part of the body. When the body uses up oxygen, carbon dioxide is produced as a waste product and is transported through the blood to the lungs to be exhaled.

The Stamler lab from Cleveland recently published in the journal Proceedings of the National Academy of Sciences that nitric oxide is a third essential component in respiration.

It turns out that a tiny block (called bCys93) on the surface of every red blood cell is devoted to carrying nitric oxide. Nitric oxide has many roles in the body, but no one knew exactly why it attached to red blood cells. Stamler’s group mutated this block so that it could not bind nitric oxide. Remarkably, mice with this mutation could not carry oxygen normally through the bloodstream. When the mice were challenged with a low-oxygen environment akin to a high-altitude mountain climb, normal mice were able to accommodate the stress, but the mutated mice were not. In other words, nitric oxide is essential for oxygen to be delivered to the body.

The results of this study suggest that it might be beneficial to include nitric oxide in blood bags for transfusions to improve oxygen uptake following blood transfusion. But it’s also time to upgrade biology textbooks with a new respiratory cycle: breathe in, breathe out and don’t forget the nitric oxide!

Source: “Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia,” Rongli Zhang, PNAS, DOI: 10.1073/pnas.1502285112

Emily Johnson, PhD, is an APS member and a former volunteer editor for the I Spy Physiology blog.