1. Oxygen transport in humans.

• In vertebrates, oxygen is carried by hemoglobin (Eckert, Fig. 13-2a) located in the erythrocytes (red blood cells) and stored in muscle tissue by myoglobin. Hemoglobin consists of four protein subunits, each containing a non-protein heme group (Eckert, Fig. 13-2b). Oxygen binds to the heme. (There are some exceptions to the presence of hemoglobin or similar molecules in vertebrate blood - the Antarctic Icefish has NO respiratory pigment at all.!)
• Oxygen binds to the Iron. This causes the Iron atom to move closer to the plane of the porphyrin ring. This pulls a histidine closer to heme plane (Eckert, Fig. 13-2c) -> moves the alpha helical segment containing the histidine towards an adjacent helix. This movement pushes a tyrosine which moves the C-terminal (the end of the protein chain with the COO-). In hemoglobin, the C-terminal forms an ionic bond with a positively charged residual group on an adjacent subunit, holding the subunits together. Movement of the C-terminal therefore affects the shape of the adjacent subunit and its ability to bind oxygen.
• Binding of oxygen to hemoglobin is cooperative. Binding of an oxygen molecule to one of the four subunits results in shape changes in the other three subunits, increasing the affinity of these other subunits for oxygen.
• Sickle cell hemoglobin is a genetically based disease in which one nucleotide base is different from normal. This mutation is on the gene which makes the beta chain of hemoglobin and causes a change a different amino acid to be substituted at one location on the beta chain. This substitution causes hemoglobin molecules to bind together in clumps, resulting in water loss from red blood cells. Shrinkage of red blood cells causes them to clog capillaries and prevent normal circulation.
• The gene for sickle cell hemoglobin has a single nucleotide base mutation that causes a substitution of valine (GTG codon) for a glutamic acid (GAG codon) on the beta chain. The sickle cell trait is found in about 8% of African-Americans. Hemoglobin C, found in about 2% of African-Americans, is produced by a gene that has a point mutation at the very same site as for sickle cell hemoglobin, but in this case causing substitution of lysine (AAG codon) for glutamic acid. Hemoglobin C doesn't pose significant health problems for those who have the trait.
• Carbon monoxide (CO) binds to the heme/iron group in place of oxygen, thus preventing normal oxygen binding to hemoglobin. Oxygenated hemoglobin is bright red in color and deoxygenated blood is more of muddy dark red color. (Deoxygenated blood is NOT blue, one of the great myths! The blue color of some veins is due to the tissue, not the hemoglobin. Carboxyhemoglobin (CO bound to hemoglobin) is bright red, because the hemoglobin has mistaken the CO for O₂. In cyanide poisoning, the cyanide blocks cellular respiration by binding to cytochrome oxidase in the electron transport chain. The blood also looks bright red because oxygen isn't being used by the peripheral tissues.
• Oxygen transport can be understood by looking at the binding curves for oxygen to hemoglobin and myosin.

• When hemoglobin is bound to CO or there is less hemoglobin present, as in anemia, the maximum capacity of the blood to bind oxygen is reduced (Oxygen binding curves with CO present).

2. Invertebrate oxygen binding pigments

• Hemoglobin is found in invertebrates but some invertebrates have other types of heme pigments, including hemerythrin, chlorocruorin, and hemocyanin. Some invertebrates have no respiratory pigment at all. Read the small paragraph on invertebrate respiratory pigments in your text, pg. 531. As an example of how some invertebrate respiratory pigments are used, note that the hemocyanin of Limulus, the horseshoe crab, consists of 48 subunits, not four as in hemoglobin. Hemocyanins and other invertebrate respiratory pigments dissolve directly in the blood, not in blood cells. Hemocyanins use two copper atoms to bind oxygen instead of one iron, as in each subunit of hemoglobin.

3. Carbon dioxide transport in humans.

• Carbon dioxide reacts with water to form carbonic acid that then dissociates into H⁺ and bicarbonate. This reaction can be catalyzed by the enzyme carbonic anhydrase, that speeds up the conversion by as much as ten million times!!!! Carbonic anhydrase is found inside the red blood cells but not in the blood plasma. The linked figure shows the active site of carbonic anhydrase, with the zinc atom held by the histidine side chains of the protein. Note that hemoglobin uses histidines to hold the heme group containing an iron atom.
  

• Carbon dioxide diffuses from tissues into the blood plasma and then into red blood cells. Some of the CO₂ binds to amino groups on hemoglobin, but most is converted into bicarbonate. (Eckert, Fig. 13-10a) These reactions are reversed in the lungs (Eckert, Fig. 13-10b). QUESTION - Why are the reactions reversed in the lungs? We will see one part of the answer in conjunction with the Haldane effect. Can you think of another, even more basic reason?

• Bicarbonate transport across the red blood cell membrane involves simultaneous transport of chloride in the opposite direction. This transport, by Band III protein channels, is known as the chloride shift

• The Haldane effect: (Eckert, Fig. 13-11 - FIGURE CORRECTED AND MODIFIED)

All text and images, not attributed to others, including course examinations and sample questions, are Copyright, 2008, Thomas J. Herbert and may not be used for any commercial purpose without the express written permission of Thomas J. Herbert.