Carbon Monoxide Poisoning

This post was requested several weeks ago.  My apologies in not pulling it together sooner.

Also?  The hemoglobin protein is directly involved in Sickle Cell Disease.  Check out a small blurb on this subject on Mini-Amedeo - LINKY. (http://miniamedeo-amedeo.blogspot.com/2012/01/sickle-cell-trait.html)

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                We’ve all heard of it.  We all think we understand what it does.  We’re all convinced it’s red.  Such is the general knowledge of hemoglobin.  Now, I’m going to take you now on a guided tour of this protein.  Come along.

                Figure 47.1 shows you one molecule of hemoglobin.  It’s a small protein (the α subunit for humans is only 142 amino acids, P69905).  You’ll notice, however, that hemoglobin isn’t solely comprised of amino acids!  There is a large, flat molecule associated with it called a heme group (colored red).  

Once the protein has been created by the ribosome (Central Dogma post…), a heme group nestles itself inside the hemoglobin protein molecule.  Heme groups are not protein.  They are not encoded by our DNA.  They are simply molecules that our cells make for the sole purpose of sticking them inside hemoglobin.  Think of lovely wrapped present.  The hemoglobin protein is the wrapped box and the heme group is the bow – tacked on the top, but totally completes the package.

Figure 47.2 shows you exactly what a heme group looks like.  Don’t worry, you only need to understand one thing about the heme group: it binds oxygen.  This means that a hemoglobin protein without a heme group cannot bind oxygen.  It is, in essence, useless.

Hemoglobin is an interesting protein.  

For one, it is a tetramer.  The picture in Figure 47.1 is not complete.  Some proteins are content to hang out on their own but others like to be in groups.  Hemoglobin is one of those proteins.  In fact, it likes to be in groups of four.   This means that the mature hemoglobin proteins in our blood look essentially like the above picture times four.  This is shown more easily in Figure 47.3.  Each individual molecule carries its own heme group so this means that a tetramer of hemoglobin can bind four oxygen molecules total.

Secondly, hemoglobin helps itself bind oxygen.  This property is called cooperativity.  When one heme group within the tetramer binds oxygen, it becomes more likely that the other heme groups in the tetramer will bind oxygen.  It may seem like an odd concept at first, but oxygen is crucial to our survival.  Hemoglobin’s job is to pick up oxygen at our lungs and then carry it to various places in our body.  Anything that will make the pick-up of oxygen more efficient, such as the cooperative nature of oxygen binding, is greatly desired.

The left of Figure 47.4 shows you what oxygen looks like.

The right of Figure 47.4 shows you what carbon monoxide, also called CO, looks like.

My, my.  They look really similar, don’t they?

They actually are really similar.  

Sadly, they have one huge difference.  Oxygen likes binding to the heme group in hemoglobin, but is perfectly content popping off when needed.  Obviously, hemoglobin is meant to drop oxygen off at cells so the oxygen must be able to get off the heme group when necessary.  Carbon monoxide, however, has no interest in getting off.  It loves the heme group and will stay there.  Forever.

This leads to a two-fold problem when a person continues to breathe in carbon monoxide.

One.  All the hemoglobin traveling to the lungs to pick up oxygen are picking up carbon monoxide instead - carbon monoxide that will never get off their heme groups.  The amount of oxygen available to your cells is going to drop rapidly.

Two. Oxygen is important to your cells.  Everyone knows that we breathe oxygen in and carbon dioxide out (plants do the opposite!), but what is its role once inside the body?  I touched on it briefly in the post Conferencesand Cancer Cells, Part 2.  I’ve placed Figure 21.1 below that reviews how the cell gets energy (which is called ATP).  Oxygen is crucial to the last step, called the Electron Transport Chain.  If oxygen is not around, that entire diagram stops running, which means that the cells are now starved ATP.  Without energy, many essential biological processes simply stop and cells begin to die.

                Carbon monoxide is ordorless, colorless, etc…  You can’t see it or smell it and there’s no way to know there’s a problem until it’s far too late.  Some people have carbon monoxide detectors in their homes.  Many know not to stand in a closed garage with a car running.  Be wise about carbon monoxide.

                This entire post reminds me a scene from the movie “The Client.”  Jerome “Romy” Clifford drives out to a deserted area, runs a hose from his exhaust pipe to the window of his car and tries to kill himself.  It would have worked nicely if it wasn’t for the two kids who happen upon him.  Good movie; better book (John Grisham).  Go read it!

Heme group: a special group of molecules that binds to hemoglobin and is responsible for binding oxygen.

Tetramer: Protein molecules sometimes come together to form higher order groupings.  A single, functional protein is called a monomer.  Two protein molecules that come together are called dimers.  Three = trimers.  Four = tetramers.  This goes on as high as you can imagine…

Cooperativity: The act one of process helping another (there’s more to this definition, but let’s leave it at that for now).

REFERENCES

Zumdahl, Steven S. “Chemical Principles, 4^th Edition” (2002) Houghton Mifflin Company, Boston, MA.

Alberts et al. “Molecular Biology of the Cell, 4^th Edition.”  Garland Science, New York, New York. (2002).

Grisham, John.  “The Client” (1993) Bantam Dell, Random House.  New York, New York.

Hemoglobin PDB code: 1HHO, pictures were made in PyMOL