HAEMOGLOBIN: the intelligent protein - (Jan/27/2007 )

hi,


a wonder comes to my mind about the function of haemoglobin and i want to discuss it here with you...
as you know, Hb transports O2 from lungs through blood vessels to the various parts of the body, and on the opposite, transports CO2 from body parts to the lungs....
my Q. here, what makes this protein able to bind two molecules (dual affinity) and how could it "know" where to lift one molecule and bind to the other ??
i think it could be the pH values....

what do you think

---

blame that on transitional metal chemistry. Transitional metal ions have the wonderful and somewhat complex behaviour of an expended electron shell... ie the energy levels different orbits become so close together that they can easily be made to mix and accept lone electron pairs which are found on many many molecules... like water, cyanide, carbon monoxide, nitrogen oxide, ammonia, oxygen, nitrogen etcs... read more in a chemistry text book.

As a transitional metal, iron isn't that special. We use iron in our blood, but other creatures namely crustacean use copper. Use of iron is by far more common because iron is a rather common metal on earth. And that can be blamed by the fact that in nuclear synthesis, iron is the peak of nucleii stability. ie you can't get more energy by fusing iron. All elements higher then iron take energy to make. So when a star dies, you get plenty of iron.

And finally hemoglobin is not dual affinity. Due to the protein change around the heme group (which prevents oxidation and binding to large molecules) hemoglobin will bind to any small molecule with lone pair electron. Haemoglobin will bind to carbon monoxide (very strongly, in preference to oxygen thus carbon monoxide poisoning), cyanide (though this cause of cyanide poisoning.. cyanide inhibits the electron transfere chain... thus will kill that way before causing asphyxia) and nitrogen oxide



pH is one. Haemoglobin changes shape in responce to pH. High pH (from carbonic acid) cause a conformational change which makes the protein more likely to release oxygen and more likely to bind carbon dioxide.

Carbon dioxide. Carbon dioxide binds to another site on the hemoglobin protein. Again this cause a conformational change which makes the molecule less able to hold onto oxygen.

Coperative oxgen binding and release. Hemoglobin is a tetrameric complex. Binding of oxygen on one protein causes a shift in the tetramere, making the other molecules more likely to bind to oxygen... thus a sigmodal curve for binding affinity to oxygen. Which means that at set oxygen concentration, hemoglobin rapidly takes up oxygen and below another oxygen concentration, there is a sudden release of oxygen.


And just in case any creationist comes looking, this is not evidence of GOD aka an Intelligent Creator. If an Intelligent Creator was around another element other then iron would have been used. A more 'intelligent' replacement for iron would be copper, less abundant and harder to obtain but will give resistence to carbon monoxide poisoning. And it'll resolve the need to have my boiler inspected every year. In the matter of oxygen carrying molecules, man is the not the penultimate species of the Inteligent Creator, it is the Horse-shoe crab.

---

Perneseblue: Yes, you´re right but I think that "Haemoglobin changes shape in responce to pH" is not that right. Because as we all know, pH of blood is tightly regulated (7,35 - 7,45) so there are no significant changes in erythrocytes. And one more thing, hemoglobin changes conformation because of oxigen binding on His 7 mainly, so this incite Hb to change the conformation and thus increases his affinity to bind other oxygen molecules . . . But I like your explanation, why It shoud be iron !

---

thanks for the compliment.

I might be mistaken, but if I recall correctly the blood in the aveolli and very active tissue (ie muscles at work) have blood pH a little different from normal blood pH. the change in pH is slight 0.2 but is enough to cause and show hemoglobin's reaction to changes in pH.

Blood in the aveolli is slightlly more basic, due to removal of hydrogen (by recombination with bicarbonate ions and release of Carbon dioxide - triggered by change in partial pressure of CO2)

Blood within capilarries moving through actively respiring tissue can get a little more acidic due to active respiration of said tissue.

---

Yes, It can be, but it is changing only during work (in your case) - so called metabolic acidosis, because of lactic acid. We also have to count with respiratory and metabolic acidosis and alcalosis, but blood pH must not change significantly, just withing range I´ve written. So, when we are at rest, there is no need to change pH "dramatically", thus I think pH does not influence Hemoglobin conformation But maybe Im wrong too

---

hi, thanx for your comments
pernesblue, away from theories , i want to discuss the scientific base behind the function of haemoglobin.....pH is only one propable reason..
based on what u said that iron can bind with any molecule having a lone pair of electrons....maybe iron is not the key here, haemoglobin grooves may affect the binding
why couldn't it be the difference in concentration in O2 or CO2 between the blood vessel and the tissues .....in case of muscles for example, oxygen molecules are supposed to cross vessel membranes to enter low-O2 cells and CO2 molecules move to the low-CO2 blood vessel...

---

---

I think I have caused a missunderstanding. So to clear up this muddle, I should state.

"pH change is not the most important factor for hemoglobin discharging oxygen. It is one of the factors"

It is the partial pressure of oxygen ie its' concentration in solution that is most important.
-next factor on the list is carbon dioxide binding to the hemoglobin protein.
-the next factor after that is pH. Hemoglobin is very sensitive to pH. A slight shift will cause a large effect. pH change of 0.2 is enough to bring Hemoglobin from a near saturated state to a near discharged state. The muscle example is a special case of off loading oxygen. But the lung example is more common, ie the loading of oxygen.

-So on the matter of pH, it is an adjustment dial, a hair trigger one that makes hemoglobin more sensitive to its surroundings.

The pH of blood in arteries and veins is stable. But you will discover variations in capilaries especilly those surrounding aveolli and actively respiring red muscle.

Hmm... I think books on inorganic chemistry will help. They love hemoglobin, Vitamine B12 and chlorophill as example. Strawberry, I think you will find the norminal biology section of said books useful.

The binding of oxgen is an intrinsit part of iron II ions. Mediated by expended electron shell that can capture's lone pair electrons from the dimolecular oxygen.

It is the porphyrin planar cage that prevents the iron II ions being oxidised by oxygen to iron III. The strenght of binding between oxygen and the iron ion is influence by the surrounding amino acids, iron can bind 6 lone electron pair. 4 from the porphyrin ring, one on top is left free to bind oxygen and one at the bottom is bound to an amino acid. Tugging the iron ion downwards, weakens the binding to oxygen.

Of course the amino acids around the porphyrin ring also influence selectivity. Only small molecules can get near the iron ion. Like OO, NO and CO. Not any compound with a lone electron pair can reach the porphyrin ring.

---

thanx pernesblue for clearing the picture...i've to look deeper into atoms and electrons..
glad to know that my guess about concentration is right..

---