Hemoglobin

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Hemoglobin is a protein

    Like other proteins, it has a primary, secondary, tertiary, and even quaternary structure.  We will go through those structures of hemoglobin.  Yet, hemoglobin is a bit more complicated than simply those structures.  The hemoglobin molecule actually contains another molecule within it, called soundicon.gif (538 bytes)heme.   The heme molecule itself is rather complicated, and will be explained farther down on this page.

    I'm going to go into as much detail here as your book does.   However, your book goes into that much detail by throwing in pictures and words here and there without a great deal of explanation.  So, my description of hemoglobin will seem much more detailed.  It only is so detailed, however, to explain what's in your book.  I won't ask you tons of detailed questions.  I just want you to understand this pretty complicated molecule.

Let's start with the plain-old-protein portion of hemoglobin:

    The protein hemoglobin is made up (primarily) of 4 polypeptides.   Remember that proteins are built by taking amino acids and stringing them together into long chains called polypeptides.  Each of the 4 polypeptides is necessary to make one full hemoglobin molecule.  Typically, when a protein is made up of multiple polypeptides, each polypeptide is simply called a protein subunit.  However, in the case of hemoglobin, the subunits are each called globin.  In other words, a globin is the same thing as an individual polypeptide of hemoglobin.  The idea behind the nomenclature is that when you add 4 globins and 4 heme groups together, you get a hemoglobin.  I'll come back to that.  Let's continue with the protein portion.

    The 4 globins are of two types.  2 of them with identical amino acid sequences (primary structure) are called alpha-globins (a-globins), while the other 2 also have identical amino acid sequences and are called beta-globins (b-globins).  Every hemoglobin molecule contains 2 a-globins and 2 b-globins.   It's not like the a and b -globins are that different, they are pretty similar... that's why they are both still called globins.  It's just that they are the teensiest bit different.  The whole idea of the two different globins may seem quite miniscule to you.  But, even tiny differences in primary structure of polypeptides can cause dramatic differences in protein function.  This is best exemplified by learning a little bit about sickle-cell anemia.  There's a description of this disease at the bottom of this page.

    Each of the globins is folded into a secondary and tertiary structure.  Then, all four are put together into the hemoglobin molecule's quaternary structure.  This image 4globins.gif (6097 bytes)shows each of the 4 globins in a different color.  Each globin is represented by a line-- that line reflects the way the individual polypeptide chain is folded.  In some places, you'll see that line looks like it is all curly-cued-- that is when the secondary structure is in its helical form.  Note that the entire colored line is bent upon itself to wrap up into a bit of a ball shape-- that is the tertiary structure of the globin molecule.To see this a bit more, go to this NIH web page.   At this page, select "backbone-JAVA" from the drop-down list indicated by Output Requested.  Then click on "submit request."  You will then be able to click on an image that looks a bit like this one here, and rotate it in 3D.   I think you'll find it interesting to see.

    Here are a few more views of the four globins of hemoglobin:

     Each globin is a different color at the left.  A ribbon is used in these drawings rather than a line.  On the right, everywhere it is pink, the secondary structure of the globin is a helix.  Quite helical, huh?

HGribbon.gif (22233 bytes) HGhelix.gif (20245 bytes)

HGspacefill.jpg (13794 bytes)

    This image is a "space-filling" model of hemoglobin.   Every atom takes up more space than can be indicated with a line or a ribbon.   I just wanted you to see this so that you didn't picture the hemoglobin molecule as full of holes!  It really is quite compact.

 

 

 

 

The heme group

    Each globin is associated with a heme group in its center.  I know, I just showed you how packed a hemoglobin molecule is.  But, right in the middle of each globin is a bit of space in which the heme group will fit.  HGwheme.gif (46389 bytes)Take a look at this picture of hemoglobin, where the ribbon is shown as a set of thin gray lines, so that the globin appears a bit transparent.  I can't remember where I found this image so I can't reference it here.  I do know that it seemed OK to use it for educational purposes.  I will have to look for it to find the appropriate reference.

    In the middle of each you can see a side-view of the heme group.   It is the stuff in the middle of each globin shown with the space-filling model, so that the atoms appear gray, red, and yellow.

    What is a heme group?  It is an organic molecule, arranged in a circle, with an iron atom in the middle.  The organic molecule, when straightened out (not in a circle) is called soundicon.gif (538 bytes)biliverdin.   However, in a circle, it holds an iron atom (Fe) in its center.  A nice image of this is in your book in Figure 14.5.

    The iron atom (in collaboration with the rest of the heme molecule) is the portion of the hemoglobin molecule that gives the entire molecule oxygen-attracting properties.  When oxygen binds to the hemoglobin molecule, its association with the iron atom causes a change in color of the entire molecule.  You should be able to understand this if you think about iron and other metals in general-- what happens to iron if it is left out for a while?  It changes colors.  All metals tarnish with exposure to air.  That's because the oxygen in the air "oxidizes" the metals.  Well, when oxygen combines with hemoglobin, the entire molecule turns a bit redder.

hemoglobin = 4 globins + 4 heme groups

oxyhemoglobin-- hemoglobin that is carrying oxygen, it is bright red

deoxyhemoglobin-- hemoglobin that is not carrying oxygen, it is purplish-bluish-red

What happens to the hemoglobin when a red blood cell dies?

    Iron is one of those things that we need in our bodies in small amounts.  We get iron in our foods (especially meat, since muscle is so highly vascularized), and certainly, we can't ingest straight iron!  Since we need iron, but it is not always easy to get anew, our bodies need to preserve as much iron as possible.

    Therefore, when our red blood cells die, we need to extract back out the hemoglobin that they contained.  Here's what happens.  the red words are the ones that relate to what happens to the iron atom

bulletafter RBC death, hemoglobin leaks out (typically into the blood)
bullethemoglobin disassembles outside of the RBC into 4 globins plus 4 heme groups
bulletthe globins can be broken down and re-used for its amino acids
bulletthe heme groups unfold and the iron atom leaks out:  this produces one biliverdin molecule plus one iron atom for each heme group
bulletthe iron quickly binds to a plasma protein called transferrin, which carries the iron through the blood either to bone marrow for more hemoglobin production or to the liver for storage (it is called transferrin not because it transfers iron, but because ferrin stands for the Latin name for iron, that's why it iron is represented by "Fe")
bulletmuch of the biliverdin (a greenish molecule, verdi- stands for green) gets changed into bilirubin, which is an orangish molecule
bulletthe biliverdin and bilirubin end up being released by the gallbladder into the digestive system within the gallbladder secretion which is called "bile," and they can be broken down for use and excretion in the digestive system

    We haven't looked at how our bodies recycle organic material before... so why are we doing it now?  First of all, because of the importance of the iron atom being recycled.  But also, because if you think about how many red blood cells are in any one person, as I show you in the table below, you'll realize what a huge amount of total body material they make up... we can't just destroy all that, we have to recycle it.

How many red blood cells exist in one person?

Each person has about 5 liters of blood (see page 521) which is 5000 mLs of blood!
There are around 5 million RBCs in one cubic millimeter (see page 524)

How do we get from cubic millimeters to liters?

Use cubic centimeters (cc's)!  This unit might be familiar to you,
since it is the measurement that syringes use.

1 cubic centimeter = 1000 cubic millimeters
     Therefore, 1 cc of blood contains 5 million x 1000 RBCs, or 5 billion RBCs
1 cc is the same thing as 1 mL (one milliliter)
There are 1000 mL in 1 Liter
Since each person has 5 liters of blood, there are 5 billion x 5000 red blood cells in one human body.  That is 25 trillion red blood cells in one body.

Sickle-cell anemia

    In sickle-cell anemia, the red blood cells have an odd-looking, bumpy shape and cannot carry oxygen very well.  The entire reason for this is because ONE of the amino acids in the globins is altered.  Just one amino acid.

    A change in the amino acid sequence is a change in the "primary structure" of a protein.  This influences the way the secondary and tertiary structures form.  The one amino acid substitution causes the globins to fold in an irregular way, and forces the heme group to be less effective at carrying oxygen.   Amazing, isn't it?

    A person can either have this disease or be a carrier for it.   Genetically, this isn't a case of simple dominant and recessive forms of the disease.  People who are "carriers" actually express the anemic-type of hemoglobin molecule in half of their red blood cells; carriers don't usually have much difficulty obtaining enough oxygen.

    One little caveat:  hemoglobin can also transport CO2!!!   About 20% of all blood CO2 is carried this way.  The CO2 does NOT bind to the heme group... it binds to the globin portion of the hemoglobin.   In this manner, one hemoglobin molecule can transport both oxygen and carbon dioxide gases at the same time!

From here, either go up a level to continue your RBC study by looking into blood types, or move on and study white blood cells.

 

To read this page translated into Romanian, please visit this site; the translation is by Alexander Ovsov.

2011 STCC Foundation Press
written by Dawn A. Tamarkin, Ph.D.