Haemoglobin, the oxygen-carrying protein in our red blood cells, binds oxygen at the lungs and releases oxygen at the tissues to sustain metabolic needs and, thus, life. In nearly all vertebrates, carbon dioxide, a product of metabolism, helps haemoglobin release oxygen at the tissues by acidifying red blood cells. Bony fish have ‘Root haemoglobins’ – special haemoglobins that are more pH sensitive than those of other vertebrates. Root haemoglobins help fish deliver oxygen to the retina and gas bladder, two extremely oxygen-demanding tissues. These tissues have specialized acid-producing cells that help them get lots of oxygen from haemoglobin. Other tissues do not have acid-producing cells, but is there a way that these other tissues can take advantage of the sensitivity to pH of Root haemoglobins in order to get more oxygen? Jodie Rummer from the University of British Columbia, Canada, and her colleagues recently discovered the answer to this question and their findings are published in Science.

First, Rummer and colleagues wanted to determine whether they could make fish muscles pick up more oxygen by simply making their blood more acidic. They monitored the oxygen level in trout muscle in real-time by inserting a very small probe into the muscle. Even though they applied only a moderate acid stress, the oxygen in the muscle increased by 65% and there was an approximate doubling in the delivery of oxygen to that muscle. The team calculated that Root haemoglobins are 20 times more efficient at delivering oxygen to a fish's muscle than human haemoglobins are at delivering oxygen to our own working muscles!

Fish red blood cells contain an acid pump that can pump out acid from the red blood cell, increasing pH inside the red blood cell, and making haemoglobin better able to pick up oxygen at the gills during stress. Rummer and her colleagues hypothesized that the red muscle capillaries of fish have high levels of carbonic anhydrase – an enzyme that produces carbon dioxide. As one of the fastest acting enzymes known, it could quickly acidify the blood, which would undermine the action of the acid pump, as carbon dioxide readily diffuses into the red blood cells. As a consequence, the pH in the red blood cells would be lower when they entered the capillaries near the muscle and the Root haemoglobins would release more oxygen and therefore increase oxygen delivery to the muscle. Rummer and colleagues used the same experimental setup as before, but this time added a carbonic anhydrase inhibitor to the fish's blood. This time the oxygen in the muscle did not increase. This showed that carbonic anhydrase found in the capillaries of muscles was necessary for the enhanced oxygen delivery to that tissue.

Rummer and colleagues have shown for the first time that Root haemoglobins help fish deliver oxygen to all tissues, not just the retina and the gas bladder. More importantly, Root haemoglobins are responsible for the extraordinary capacity of bony fish for oxygen delivery, allowing this vertebrate group to successfully conquer almost every body of water on the planet.

J. L.
D. J.
C. T.
C. J.
Root effect haemoglobin may have evolved to enhance general tissue oxygen delivery