ALTERNATIVES TO OXYGEN UPTAKE, TRANSPORT AND DELIVERY

From quantamagazine

TEMPORARY REPLACEMENT OF HEMOGLOBIN, RED BLOOD CELLS AND  OXYGEN UPTAKE

There are many patients in this world with pulmonary fibrosis (permanent respiratory failure) and severe aplastic anemia (failure to produce blood), being the treatments based on oxygen administration and blood transfusions. Although in the last decades lung and bone marrow transplants have been started, some problems persist (rejection of tissue transplanted due to tissue incompatibility, lack of donors and so on), being required broader medical visions to solve these diseases. Perhaps by turning our gaze towards nature, we can find successful answers, such as the temporary (or permanent) substitution of human blood and/or obtaining environmental oxygen (O2), by alternative mechanisms to those carried out by human lung alveoli. To the family Channichthyidae, belongs a vertebrate fish (icefish), native of Antarctica, with black fins, lack  of scales, transparent bones and colorless blood, lacking in pigments of hemoglobin (Hb) and  red blood cells,  which obtain O2 from the cold Antarctic waters by diffusion to back pressure through gills towards their blood plasma. Neither blood has to be red, nor oxygen transport always have to be linked to the hem fraction of red blood cells. In most environments, icefish mutation (s) would have been fatal, but not in the frigid Antarctic waters where O2 is much more dissolved than in warm waters. Regarding the emergence of Hb, some scientists believe that it should go back to the origin of the first cells that tested a series of pigments to choose it. According to Nature Ecology & Evolution,in icefish, their genomes developed adaptations: extra genes, to produce antifreeze blood proteins, increase of enzymes to protect the tissues from the side effects of O2, in the blood. Only vertebrates have red blood cells and Hb, given the extreme natural affinity of the body for O2. Invertebrates use other metalloprotein pigments in their blood. Insects and arthropods use hemocyanin, a bluish pigment that contains copper and others: greenish chlorocruorine. The first cells were urged to mobilize electrons (oxidation-reduction), outside and inside their limits as part of their metabolism, generating molecules in the form of rings (porphyrins), which retained an iron or copper atom which developed great affinity for the O2. Hb is the interconnected product of 4 globin proteins, each holding a heme. According to Mark Syddall (American Museum of Natural History), the first cells breathed by simple diffusion. By then, Hb was ready and, with each O2 molecule trapped by the pigment, the following were more easily captured. The Hb turned out to be very efficient to capture O2 from the open air and from the lungs, gradually releasing it to tissues deprived of it. The hemocyanin used by invertebrates was less efficient than Hb, to capture O2 because it did not work collaboratively as the constituents of Hb. However, human Hb does not behave efficiently when O2 is low, decreasing its effectiveness with the fall in temperature. Conversely, for octopus that live near the floor of the cold ocean, hemocyanin is better. In insects the equivalent of blood is hemolymph, a clear liquid, which contains small amounts of hemocyanin, that  can remain in the hemolymph by storing O2 for later use. Although another pigment: hemerythrin, only has ¼ of the capacity of the O2 of Hb, suitably serves worms that use it. Although insect pigments do not have a high affinity for O2, they do not need red blood cells to maintain it. On the other hand, because hemocyanin, hemerythrin and other pigments are bigger, they have to polymerize to molecules, keeping metal atoms attached to O2, away from casual metal interactions. Hb is small and its heme highly reactive and toxic, so the liver produces haptoglobin to remove Hb from broken human red blood cells. Hb also has a high affinity for nitric oxide, so that an excess of free Hb can capture blood nitric oxide that potentially can cause hypertension and reduced blood flow to body organs. On the other hand, the naked heme molecules attack the membrane lipids damaging other structures. Proteins isolated from globin can clog the filtration system of the kidneys. As seen, the evolution of red blood cells was optimized for a better distribution of O2: ejecting its nucleus and other organelles producing greenish compounds (biliverdin), less toxic. By packaging the Hb inside the red blood cells, its toxicity was  avoided. Hb is not the ideal molecule to transport O2 in all circumstances, being possible to avoid   the use of red blood cells and Hb, replacing them with other pigments like to those used by current invertebrates. With the current technology, perhaps it would be soon possible to use artificial gills attached to the most capillarized parts of human skin, injecting temporarily through it backpressure O2 and simultaneously  expelling  CO2.