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Hemoglobin: Oxygen transport in mammals

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  • Introduction to Hemoglobin

    Hemoglobin, a polypeptide found in red blood cells, allows dioxygen (O2) to be transported within blood from the lungs to other tissues within the body. Hemoglobin is a polypeptide found in red blood cells. It allows for the transportation of O2 from the lungs to other tissues within the body. Dysfunctional hemoglobin results in anaemia (iron deficiency) within the blood. However, a total lack of functioning hemoglobin would surely result in death due to deficient O2 transportation within the human body. This molecule also is also responsible for the color of blood.1 Oxygenated blood is a bright red because hemoglobin absorbs green light of wavelengths 540-542 nm, and thus it results in a bright red colored solution.2 Deoxygenated blood, however, is darker in color because it absorbs a more yellow/green color of wavelength 554 nm, and thus produces a darker color of red. 

    Hemoglobin is able to transport oxygen within the body due to its unique structure. Its structure consists of four globin subunits: two α and two β subunits. Each subunit contains a heme prosthetic group with an iron bound (Figure 1). Hemoglobin exists in high concentrations in the cytoplasm of red blood cells, so it needs to be very soluble in aqueous cytoplasm. This requirement is reflected in the protein's globular shape, and the fact that it is folded in such a way that hydrophilic residues are found on the surface of the protein exposed to water, while hydrophobic residues are found on the interior of the protein. This folding enables hemoglobin to have a stable fold in aqueous solution that also allows the protein to interact favorably with water and to be soluble in the water-filled cytoplasm of the cell.


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    Figure 1: On the left, the ribbon diagram of hemoglobin is displayed. Hemoglobin consists of four subunits: two α (blue) and two β subunits (red). A heme group (stick depiction) is located within each subunit, and within each heme an inorganic iron ion (orange) is located. Inset A: Oxy-hemoglobin has dioxygen (red) bound to the iron core of each heme group. The iron of the oxygenated hemoglobin is pulled into the porphyrin plane.  Inset B: Deoxy-hemoglobin (no oxygen bound). The iron (II) ion lies 0.4 Å outside of the porphyrin plane.  Inset C: Reversible binding of O2 to the skeletal structure of the heme prosthetic group. This group consists of four central nitrogen donor atoms bound to iron (II) (attribution: SmokefootMboxygenationCC BY-SA 4.0). Iron (II) has two axial binding sites and, in hemoglobin, one is occupied by an imidazole N of the proximal histidine. The second axial coordination site has the ability to reversibly bond to an oxygen atom.


    Applying principles of inorganic chemistry

    Much of what is known about the Fe-heme center in hemoglobin has been determined experimentally studying a similar protein; myoglobin. The structures, functions, and properties of hemoglobin and myoglobin are quite similar. The features that are unique to hemoglobin are discussed on this page, below. Please go to the article on myoglobin to learn about the inorganic chemistry of both hemoglobin and myoglobin.


    Cooperative binding of O2

    An important feature of hemoglobin is a cooperative binding of oxygen to each subunit due to conformational changes upon oxygen binding to the heme iron. Hemoglobin exists in both the T-state (tense state) and the R-state (relaxed). The T-state has lower affinity for dioxygen due to the tilting of the proximal histidine and steric hindrance of the O2 coordination site.6,12 Steric hindrance makes it difficult for oxygen molecule to enter the site and bind to Fe. When an oxygen binds to one subunit of hemoglobin, the iron shifts into the plane of the porphoryn ring, and tugs on the proximal histidine.3,9 This causes the proximal histidine ring to be pulled toward the plane of the prosthetic group, decreasing the tilt of the histidine, causing a shift in the tertiary structure of that subunit, and displacing residues that were providing steric hiderance of the oxygen binding site.12 These conformational changes in one subunit cause similar changes to the tertiary structures of adjacent subunits, in turn decreasing steric and electrostatic constraints in those adjacent units. The result is adoption of the R-state and a subsequent increase in oxygen affinity to the other subunits.12,13

    When the inorganic iron ion is bound to only five coordination sites the iron (II) lies 0.4 Å outside of the porphyrin ring.3,9,12 When the oxygen binds to the iron core the iron becomes smaller as it becomes low-spin because electrons are pulled closer to the Fe core or are transfered to the dioxygen molecule due to backbonding. The low spin iron and is able to fit in the plane of the porphyrin ring.3,9

    There is a video on the previous page that describes and shows the changes that occur upon oxygen binding to hemoglobin. Additionally, the short video below illustrates conformational differences between fully oxygenated hemoglobin and deoxygenated hemoglobin. (Click here if the video does not load).


    1. Casiday, R.; Frey, R. Washington University of St. Lous Chemistry. (accessed 6 March). 

    2. Zijistra, W. G; Buursma, A.; Meeuwsen-van der Roest, W. P. Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, Carboxyhemoglobin, and Methemoglobin. Clin Chem [online] 1991, 37, 1633-1638.

    3. Prahl, S. Oregon Medical Laser Center. (accessed 6 March).

    4. Berg, J. M.; Tymoczko, J. L.; Stryer, L. Biochemistry, 5 ed., W. H Freeman and Company: New York, 2002; unknown. 

    5. Jensen, K. P.; Ryde, U.; How O2 Binds to Heme: Reasons for Rapid Binding and Spin 

    Inversion. JBC [online] 2004, 279, 14561-14569

    1. iron (III) oxide also talks about cooperativity

    2. iron (III) superoxide

    3. Explains the oxygen dissociation curve

    4. Shriver, D; Atkins, P. Inorganic Chemistry, 5th ed.; W.H. Freeman and Company: New York, 2009; 739. 

    5. Frausto da Silva J. J. R.; Williams R. J. P. The Biological Chemistry of the Elements: The Inorganic Chemistry of Life, 2nd ed.; Oxford University Press: Oxford, 2001; 370-373, 385-386. 

    6. Crabb, E.; Moore, E., Eds. Metals and Life; Royal Society of Chemistry: United Kingdom, 2010.

    7. Low spin/high spin and cooperativity

    8. Spin-Pairing Model of Dioxygen Binding and Its Application to Various Transition-Metal Systems as well as Hemoglobin Cooperativity

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