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Getting Oxygen Where It’s Needed

Oxygen is required by many organisms for survival, luckily it is plentiful in the air, but how does it get into all the tiny cells all over the body?

periodicFirst, Oxygen is a highly electronegative atom. This means that it attracts electrons very well and can pull them away from other molecules. Only one other atom is more electronegative and that’s the most reactive element in the periodic table, Fluorine. Electronegativity becomes useful biologically because electrons are capable to storing energy that can be passed along from one molecule to the next. But , to do this, each molecule must be more electronegative than the last. Therefore, it is not surprising that Oxygen is used as the final electron acceptor in the electron transport chain of cellular respiration. This reaction is required by many organisms, and can be highly beneficial even to some organisms that can live without Oxygen. An electron transport chain is a process by which molecules in a membrane pass en electron down the line using its energy in a controlled way to extract even more energy from sugar.

But how does Oxygen get to the cells that need it? Two molecules account for much of this action, myoglobin and hemoglobin, both illustrated below:

Image

Hb- hemoglobin, Mb-myoglobin.

What this image also elegantly portrays is the amazing similarity between the molecules that belies their evolutionary relationship.

Each of these molecules is capable of binding Oxygen, but each occurs in a different tissue. ImageHemoglobin is present in Red Blood Cells, making them capable of transporting oxygen from the lungs to other tissues. Myoglobin occurs in these ‘other’ tissues, particularly muscle cells.

Despite the fact that they both bind oxygen, they do not bind it equally well under all conditions. While hemoglobin is just as good at binding Oxygen in high concentration environments (like the lung after inhalation), it is not as good at retaining oxygen when found in less Oxygen-rich environments (such as tissues like muscle).  Under these conditions, myoglobin is much better at binding Oxygen and can pull the molecules away from hemoglobin.

Recently, several groups have published new data about how subtle differences amongst proteins involved in Oxygen transport through blood and muscle result in different binding properties. In turn, the variability in these properties underlie the amazing diversity of lifestyles found in nature, from humans to birds to giant whales capable of holding their breath for up to an hour.

Image That brings us back to the electron transport chain and Oxygen’s electronegativity, where Ois used as a ‘magnet’ for the electron traveling down the pathway from one molecule to the next. As it goes it loses some of its energy, which is converted into a new form that the cell can use. Once the electron, now at a lower energy state, gets to O2, the Oxygen splits  and takes up a Hydrogen ion to form water.

So, electronegativity and binding affinity are the forces that both transport Oxygen through the body and pulls electrons from one molecule to another. Together, the movement of electrons, like that of water through a mill, powers processes that lead to the synthesis of ATP, the energy currency of the cell (see below).

 

electron-transport-chain-cpg-notes

Note the electron traveling down the chain (in pink)

Given what we’ve discussed here, how do you think a baby ever gets to pull the Oxygen away from its mother’s blood / hemoglobin?

 
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Posted by on June 26, 2013 in Uncategorized

 

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Speaking of Blood Types

We discussed blood types in General Biology today as an example of a trait where there are more than two alleles present in the population – the three most common of these alleles are the A allele (IA, IB and i). Last semester I wrote an essay here discussing this trait and how it is truly expressed (rather than the more simplified terms I used in class) and I wanted to point anyone interested in reading more about that here.

ImagedYou can also find a cute game about blood typing and transfusions at NobelPrize.org. The game emphasizes the importance of blood typing prior to transfusion and discusses which blood types are able to be transfused into what patients. Again, it’s cute and simple, but makes a good point.

 

 
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Posted by on March 28, 2013 in Uncategorized

 

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A blood typing mystery

A positive blood typing example, thanks to biologycorner.com for the figure

A commenter raised the following as an example of a highly unusual blood type pattern within a family.

 Given:

Parent #1 (female) Blood type O- (i/i,Rh-/Rh-)

Parent #2 (male) Blood type AB+ (IA/IB, Rh+/?)

Child #1 O- (i/i,Rh-/Rh-)

Child #2 Blood type AB+ (IA/IB, Rh+/?)

Is this possible?

Indeed, this is a highly questionable situation. Given that the genetics of ABO typing are fairly well described, the situation described raises a lot of flags. Assuming what is presented is an honest case, it would be extraordinarily interesting to investigate.

If I were asked to solve this, I would probably pursue the following ideas…

Before doing anything else, I would have everyone in the family re-typed. Since questions have been raised, I would insist that they were all re-typed at least three times at three facilities (or at least using different lots of the test reagents). I would also question the original typing location about the reagents used in the initial test and pursue whether any additional questionable typings were reported. Additionally, records should indicate the lots used for the original typing. I would question the company that produced these reagents about Quality Assurance and any known problems with these lots.

The commenter also indicated that he knew of several couples with this situation (which would be extraordinary). Again, this is unlikely, so the local testing facility  and its quality remain likely sources of error.

Luckily, an explanation for the Rh types of both child is possible. Assuming the father is Rh+/Rh-, and the mother is Rh-/Rh-, children could easily have either type. This is a relief, because the Rhesus gene has a large number of alleles making it more complex genetically.

Regarding ABO types, the simplest explanation for Child #1 is that it is not the father’s child. This leaves the ABO type of child#2 in question. Assuming the retyping tests suggested above come back completely supporting the original characterization, I would like to see the birth records for the child to verify that it was not adopted or even somehow ‘switched at birth’. The best verification would be an RFLP analysis of both parents and the child. This is the ‘DNA Fingerprinting’ that is talked about in the courtroom.

Probably the most interesting explanation is that the mother is a chimera. This rare condition arises when an individual starts out life as two non-identical twins that fuse early in development to become a single person. Confirming this would require a battery of RFLP tests from different locations of the body.

To be honest, I suspect this example to be apocryphal. But it provides a great example for describing how science is done. It is always important to remember that the tests we are talking about are just tools and subject to all the weaknesses of any other human pursuit. If we found fingerprints at a crime scene, we could feel quite confident that the owner of those prints was present at some time, but we don’t know with certainty that that person is actually guilty. Thank you very much for providing the topic!

 
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Posted by on November 19, 2012 in Uncategorized

 

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Blood Typing Game from NobelPrize.org

Here’s a cute little game to test your knowledge of blood typing. It includes aspects of the typing process that I did not talk about in my posts, but with the instructions provided you should be able to perform perfect typing and transfusions every time.

http://www.nobelprize.org/educational/medicine/bloodtypinggame/

 

Yes!

 
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Posted by on November 12, 2012 in Uncategorized

 

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Blood Type Genetics and Associated Issues continued

In my last post about genetics and inheritance, I asked a question about a family:

a family comes into a clinic for their flu shots and it is found that mom had type AB blood, Dad has type O blood and they have three children with type A, B and type O blood, what are all five people’s probable genotypes and what is the problem?

 

                                                Genotype      Problem

Mom:AB                      IAIB

Dad: O                         ii

Child1: A                      IAi

Child2: B                     IBi

Child 3: O                    ii                  Oops! Where did this kid come from?

After a short discussion, it turns out that Child 3 belongs to one parent from a previous marriage. Which parent’s child is this? If the other parent was homozygous, what was that person’s genotype and phenotype for ABO blood type?

It turns out that blood is even more interesting than this. There is another major blood antigen that needs to be matched when doing transfusions. This antigen is called ‘Rh factor’ because it was initially found in Rhesus Macaques, a type of monkey with a lineage close to our own. Although there are a number of Rh antigens, we are typically referring to the one that elicits the strongest immune response, the D antigen. Blood types are commonly referred to as ‘positive’ if the individual has the D antigen allele or ‘negative’ if the individual does not have this allele.

Like the ABO blood types, the Rh allele is important because of the strong immune response against it after Rh- individuals are exposed to Rh+ blood. Note that this is different than the ABO types where antibodies already exist. People only generate ‘anti-Rh’ antibodies after a primary exposure to this blood type, much like when a person is vaccinated against a disease, exposure to disease-associated antigens initiates the immune response, which will be protective upon later exposures.

This sounds like I am spending too much time in the details, but they are important in this case. To illustrate, let’s discuss the most common situation where this is important:

A woman with type A- becomes pregnant from a man with type B+ blood type.

What ABO blood types are possible from this pairing? Depending upon the genotype of the parents, it could be anything (A,B,AB or O).

But we said that it would be dangerous for blood to mix between someone with A blood type, like the mother, and any type that contained the B antigen, possibly like the baby.  So, is this baby in danger?

Thankfully, not. The reason is because the antibodies that we naturally make against the A or B antigens are typically IgM, which are very large molecules that do not pass through the placenta to the baby.

Image

The larger IgM antibody cannot cross the placenta, but the smaller IgG antibodies can

 

What about the Rh antigen?

The Rh alleles interact in a typical dominant / recessive manner. As you might expect, Rh+ means that you express the protein, and this allele is dominant over Rh-, which means you don’t express this protein. Given this, we know that the mother must be Rh-/Rh- in order for her to have the ‘negative’ phenotype. The man has the ‘positive’ phenotype and therefore must be either Rh+/Rh- or Rh+/Rh+. Either way, the child has a good chance of being Rh+ as well (50% or 100% respectively).

Unlike the antibodies against A and B antigens, antibodies against Rh are typically smaller, IgG molecules. These are capable of crossing the placenta into the child’s blood and can be very dangerous. But also unlike the A and B antigens, anti-Rh antibodies don’t exist prior to exposure, so the mother will not likely have any of these antibodies during her first pregnancy with an Rh+ child.

Because of the nature of childbirth, it is possible that a mother will be exposed to her child’s blood during birth and she may develop antibodies against Rh at this time. But child #1 is already out, so he/she is safe. The difficulty occurs when the mother becomes pregnant with a second Rh+ child. At this time her anti-Rh antibodies can cross the placenta and cause hemolytic disease in the developing baby.

Fortunately, there is a good safety against this. A Johnson and Johnson subsidiary company, Ortho, makes an antibody cocktail called RhoGAM that is given at the 28th week of pregnancy and then again within 72 hours after delivery (now there are a number of similar drugs made by other companies as well). This cocktail contains antibodies that bind to and ‘hide’ any Rh antigen in the mother’s system. In this way, the mother’s immune system never ‘sees’ this antigen and doesn’t make antibodies against Rh, making it safe for her subsequent Rh+ children.1,2

References

  1. Pregnancy (rhesus negative women) – routine anti-D (review) (TA156) http://guidance.nice.org.uk/TA156
  2. Rh incompatability. http://www.nlm.nih.gov/medlineplus/ency/article/001600.htm
 
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Posted by on November 12, 2012 in Uncategorized

 

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I’m such a wimp

My wife has been really impressive in her commitment to getting exercise in the morning. I can make myself exercise, but never in the morning – there’s just nothing about a workout that will motivate me to crawl out of a comfortable bed before the sun even comes up. Nevertheless, she’s been getting up and running of lifting weights in the basement for probably two months or more now.

Recently she was saying that it would be more helpful to have a barbell, rather than the dumbbell set have. So, to be a nice husband who listens and responds to his wife, I went out and picked up a barbell last night and was setting it up for her so it would be there for her first thing in the morning. Now, admittedly, I didn’t get the best product in the world – I just got something simple and -let’s just say it – available in Walmart. Because it was a Walmart product, I had to actually assemble the bar, which came in three pieces and had to be joined with a couple metal dowels.

So, I put it together and I was going to move it over to a good space to store it, slid my hand down the bar and sliced it open between my thumb and index finger pretty well. It wasn’t much of a cut, but it did bleed all over the place and this is where I have to admit to being a wuss: I was actually swooning and sick to my stomach. I think I almost passed out from nothing more serious than a deep scratch!

Well, at least I found the nasty part before my wife did – I would have felt a lot worse if she was the one to cut herself. In the end, it’s nothing that a good coating of duct-tape couldn’t make right. (the bar, not my hand – although, I think duct-tape would probably do a better job of sticking to my hand than this damned bandaid)

 
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Posted by on June 19, 2012 in Cycling, Personal Life

 

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