Tutorial:How do we get the oxygen we breathe: Difference between revisions
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New page: __NOTOC__ <StructureSection load='1hh0' size='500' side='right' caption='' scene='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/1hho_bio/7' > When we breathe, or respire, oxygen ... |
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When we breathe, or respire, oxygen from the air is taken up by blood in our lungs and soon delivered to each of the cells in our body through our circulatory system. Among other uses, our cells use oxygen as the final electron acceptor in a process called aerobic respiration -- a process that converts the energy in food and nutrients into a form of energy that the cell can readily use (molecules of ATP, adenosine triphosphate). The cells of large organisms like humans use aerobic respiration because other forms of energy production are less efficient, and oxygen is plentiful. (''THINK'': Do fish use aerobic respiration?) | When we breathe, or respire, oxygen from the air is taken up by blood in our lungs and soon delivered to each of the cells in our body through our circulatory system. Among other uses, our cells use oxygen as the final electron acceptor in a process called aerobic respiration -- a process that converts the energy in food and nutrients into a form of energy that the cell can readily use (molecules of ATP, adenosine triphosphate). The cells of large organisms like humans use aerobic respiration because other forms of energy production are less efficient, and oxygen is plentiful. (''THINK'': Do fish use aerobic respiration?) | ||
But, although oxygen is transported in our blood to reach each of the cells in our body, oxygen does not dissolve well in blood | But, although oxygen is transported in our blood to reach each of the cells in our body, oxygen does not dissolve well in blood. So how is oxygen transported in the blood? | ||
===Hemoglobin, the oxygen taxi=== | ===Hemoglobin, the oxygen taxi=== | ||
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=====Each monomer has a heme group===== | =====Each monomer has a heme group===== | ||
Notice that each monomer, whether α or β, has a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Four_hemes/ | Notice that each monomer, whether α or β, has a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Four_hemes/3'>molecule</scene> associated with it that is represented by several multicolored, overlapping, small spheres. These molecules are called <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/One_heome/2'>heme groups</scene>, and they are where oxygen binds to hemoglobin, which we will soon observe. Do the colors of the spheres represent the true colors of the heme group? No, they do not. Remember that we are looking at a representation of the real structure, and in this case we have artificially colored each atom in the heme according to a common color scheme called the [[CPK|Corey-Pauling-Koltun]] scheme ( {{Template:ColorKey_Element_C}} | ||
{{Template:ColorKey_Element_H}} | {{Template:ColorKey_Element_H}} | ||
{{Template:ColorKey_Element_O}} | {{Template:ColorKey_Element_O}} | ||
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{{Template:ColorKey_Element_Fe}} ). Remember too that although we cannot change the positions of the atoms in our experimentally determined protein structure, we can freely choose different ways to show, color, and connect these atoms in order to best comprehend and convey the niceties of the complex 3D structure. We have previously represented the atoms of the heme group as individual spheres in what is called a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Spacefill_heme/3'>spacefilling representation</scene>, but we could just as easily represent the atoms as very small spheres with thick lines connecting the bonded atoms in what is called a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Ballandstick_heme/3'>ball and stick representation</scene>. Notice that the positions and identities of the atoms do not change. (''THINK'': Earlier we learned that the α- and β-monomers have so far been shown in cartoon representation. Why can’t we show the heme groups in cartoon representation?) | {{Template:ColorKey_Element_Fe}} ). Remember too that although we cannot change the positions of the atoms in our experimentally determined protein structure, we can freely choose different ways to show, color, and connect these atoms in order to best comprehend and convey the niceties of the complex 3D structure. We have previously represented the atoms of the heme group as individual spheres in what is called a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Spacefill_heme/3'>spacefilling representation</scene>, but we could just as easily represent the atoms as very small spheres with thick lines connecting the bonded atoms in what is called a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Ballandstick_heme/3'>ball and stick representation</scene>. Notice that the positions and identities of the atoms do not change. (''THINK'': Earlier we learned that the α- and β-monomers have so far been shown in cartoon representation. Why can’t we show the heme groups in cartoon representation?) | ||
=====Capturing | =====Capturing oxygen===== | ||
Hemoglobin captures oxygen and transports it through the bloodstream by binding oxygen to each of its <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Four_hemes/3'>four heme groups</scene>. These <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/One_heome/2'>heme groups</scene> are prosthetic groups; they are non-protein chemical compounds that are associated with hemoglobin and are necessary for its function. Each heme is <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Heme_composition/1'>ring molecule made up of</scene> {{Template:ColorKey_Element_C}}arbon, {{Template:ColorKey_Element_N}}itrogen, {{Template:ColorKey_Element_O}}xygen and hydrogen, with a single <font color="#E06633">'''Fe<sup>2+</sup>'''</font> (iron) ion at its center, coordinated by the four surrounding nitrogens. Each heme is roughly <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Planar_heme/1'>planar</scene>, and is held in place within the monomer by a hydrophobic interactions and a covalent bond between the iron ion and a nitrogen atom in the side chain of what is termed the <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Proximal_histidine/1'>proximal histidine</scene>. Another histidine, termed the <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Distal_histidine/2'>distal histidine</scene>, helps in oxygen binding by prevents oxidation of the iron atom (which would prevent oxygen from binding) and by preventing other molecules from binding. | |||
<scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/ | |||
When oxygen is abundant, an <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Heme/1'>oxygen molecule binds to the iron</scene> in the heme group. (''THINK'': Are there other changes besides the oxygen binding to the iron ion? Why might there be other changes?) We can watch oxygen binding in the <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Heme/2'>context of an entire monomer</scene> (colored in rainbow colors from the N terminus of the monomer to its C terminus) or in a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Heme/1'>close-up view</scene> of the heme group. | |||
{{Template:Button Toggle Animation2}} | |||
=====Carbon | When oxygen binds the heme, we notice a conformation change in the hemoglobin monomer holding the heme that bound oxygen -- in other words, when oxygen binds, the monomer changes shape. The difference in conformation between the oxygenated and deoxygenated monomer turns out to be crucial for the function of hemoglobin. Remember that hemoglobin does not exist as a monomer, but rather as a tetramer. As a result, when one monomer in a deoxygenated hemoglobin molecule binds oxygen, that monomer’s conformation change forces a similar conformation change in the remaining three monomers, causing them to adopt a conformation more favorable to oxygen binding. Said differently, as soon as one monomer in the tetramer of the hemoglobin molecule binds oxygen, the other three monomers are much more likely to bind oxygen than they were before. This mechanism of accelerated binding through monomer conformation propagation is called cooperative binding. | ||
=====Carbon monoxide also binds the heme===== | |||
Here is where the laws of chemistry present us with an interesting problem: The heme group has the chemical and structural capabilities to capture an <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/O2/2'>oxygen molecule</scene>, but an oxygen molecule (O<sub>2</sub>) happens to be similar in shape and chemistry to a molecule of <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Co/2'>carbon monoxide</scene> (CO). The result is that carbon monoxide can also bind to the iron in the heme groups of hemoglobin, although the distal histidine helps prevent this. In fact, carbon monoxide binds to the heme with about 230 times the affinity of oxygen, meaning that if both gases are available, carbon monoxide will outcompete oxygen for heme binding sites. (''THINK'': We often install carbon monoxide detectors in our homes to alert us to high concentrations of this gas. Why might carbon monoxide gas pose a danger to human beings?) | |||
===Mutated hemoglobin causes sickle-cell disease=== | ===Mutated hemoglobin causes sickle-cell disease=== | ||
<scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/ | A mutation in the gene coding for hemoglobin causes a disease called sickle-cell anemia. The <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Sickle_one_protein_cartoon/1'>mutated hemoglobin</scene> results in red blood cells with a diseased, sickle shape instead of a healthy, disk shape. These sickle cells can block blood vessels due to their abnormal shape and cause damage to tissue and organs. (''OBSERVE'': Does the mutated hemoglobin look different than normal hemoglobin?) | ||
<scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Sickle_one_protein/5'>Sickle-cell hemoglobin</scene>, shown here in spacefilling representation, differs from normal hemoglobin at a single amino acid. In the mutant, the amino acid valine takes the place of glutamate as the sixth amino acid in the beta monomer chain. Glutamate, a hydrophilic amino acid, is replaced by valine, a hydrophobic amino acid, at a location on the surface of the protein, and this creates a <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Hydrophobic_spot_in_mutant/3'>hydrophobic spot</scene>. There is <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Hydrophobic_spot_in_both/3'>another relevant hydrophobic spot</scene> near the heme binding pocket in the beta-monomer that is present in both normal and sickle-cell deoxygenated hemoglobin. (''OBSERVE'': Can you find the two hydrophobic spots on the two beta-monomers in sickle-cell hemoglobin?) This second hydrophobic spot sticks to the first hydrophobic spot, present only in the mutant, causing the hemoglobin molecules to <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Sickle_hemoglobin_chain/2'>aggregate</scene> into long fibers. We show just two hemoglobin molecules stuck together, but this fiber can extend to include a large number of hemoglobin molecules in a long fiber. A <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Sickle_hemoglobin_chain_close/4'>closer look</scene> shows us the valine from the first, mutant, hydrophobic spot in hydrophobic interaction with the alanine and leucine from the second hydrophobic spot. (''THINK'': Why might these hemoglobin fibers cause sickle-cell red blood cell shape?) | |||
<scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Sickle_hemoglobin_chain/ | |||
A <scene name='User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe/Sickle_hemoglobin_chain_close/ | |||
shows us | |||
</StructureSection> | </StructureSection> | ||
==See Also== | ==See Also== | ||
*[[Hemoglobin]] | *[[Hemoglobin]] | ||
*PDB entry [[1hho]] (oxygenated, 2.1 Å) | |||
*PDB entry [[1hga]] (deoxygenated, 2.1 Å) | |||
*PDB entry [[1hbs]] (deoxygenated, sickle cell mutant, 3.0 Å) | |||
==External Resources== | ==External Resources== | ||
