CARBOXYHEMOGLOBIN: CHARACTERISTICS AND EFFECTS - BIOLOGY - 2025

The carboxyhaemoglobin is bound hemoglobin carbon monoxide (CO). Hemoglobin is the protein that carries oxygen through the blood in humans and many other vertebrates.

To transport oxygen, hemoglobin must bind to it. Max Perutz, a chemist and Nobel laureate born in Vienna in 1914 and died in Cambridge in 2002, called the oxygen-binding behavior of hemoglobin "immoral".

Structure of hemoglobin (Source: Bielabio via Wikimedia Commons)

Imagine two hemoglobin molecules each capable of binding four oxygen molecules. One already has three oxygen molecules and the other none. If another oxygen molecule appears, the question is the following: does it join the "rich" one that already has three, or the "poor" one that doesn't have any? The probability is 100 to 1 that it will target the rich molecule.

Now imagine two other hemoglobin molecules. One has 4 oxygen molecules (it is saturated) and the other has only one. Which molecule is more likely to give oxygen to tissues, rich or poor? The poorer will deliver oxygen more easily than the rich.

The distribution of oxygen in the hemoglobin molecule can be seen as the biblical parable: "… to the one who has, to him will be given and to the one who does not have, even what he has will be taken away…" (Mt, 13:12). From the physiological point of view, this "immoral" behavior of the hemoglobin molecule is full of significance, since it contributes to the supply of oxygen to the tissues.

Carbon monoxide, however, whatever the number of oxygen atoms attached to a hemoglobin molecule, "kills" them all. That is, in the presence of abundant CO, all the oxygen bound to hemoglobin is replaced by CO.

Structural characteristics

To speak of carboxyhemoglobin, which is nothing more than a state of hemoglobin associated with carbon monoxide, it is first necessary to refer to hemoglobin in general terms.

Hemoglobin is a protein composed of four subunits each formed by a polypeptide chain known as globin and a group of non-protein nature (prosthetic group) called the heme group.

Each heme group contains an iron atom in the ferrous state (Fe ²⁺). These are the atoms capable of bonding to oxygen without oxidizing.

The hemoglobin tetramer is made up of two subunits of alpha globin, of 141 amino acids each, and two subunits of beta globin, of 146 amino acids each.

Forms or structures of hemoglobin

When hemoglobin is not bound to any oxygen atom, the structure of hemoglobin is rigid or tense, due to the formation of salt bridges within it.

The quaternary structure of oxygen-free (deoxygenated) hemoglobin is known as the “T” or strained structure, and oxygenated hemoglobin (oxyhemoglobin) is known as the “R” or relaxed structure.

The transition from the T structure to the R structure occurs through the binding of oxygen to the ferrous iron atom (Fe ²⁺) of the heme group attached to each globin chain.

Cooperative behavior

The subunits that make up the structure of hemoglobin show a cooperative behavior that can be explained with the following example.

The deoxygenated hemoglobin molecule (in the T structure) can be imagined as a ball of wool with the oxygen-binding sites (heme groups) very hidden within it.

When this tense structure binds to an oxygen molecule, the speed of binding is very slow, but this binding is enough to loosen the ball a bit and bring the next heme group closer to the surface, making the speed with which it binds the next oxygen is higher, repeating the process and increasing the affinity with each bond.

Carbon monoxide effects

In order to study the effects of carbon monoxide on the blood transport of gases, it is first necessary to describe the characteristics of the oxyhemoglobin curve, which describes its dependence on the partial pressure of oxygen to "charge" or not with oxygen molecules.

The oxyhemoglobin curve has a sigmoid or "S" shape that varies as a function of the partial pressure of oxygen. The graph of the curve emerges from the analyzes made to the blood samples used to construct it.

The steepest region of the curve is obtained with pressures lower than 60 mmHg and at higher pressures than this, the curve tends to flatten, as if reaching a plateau.

When in the presence of certain substances, the curve can show significant deviations. These deviations show changes that occur in the affinity of hemoglobin for oxygen at the same PO ₂.

To quantify this phenomenon, the measurement of the affinity of hemoglobin for oxygen was introduced, known as the P ₅₀ value, which is the partial pressure value of oxygen at which hemoglobin is 50% saturated; that is, when half of its heme groups are attached to an oxygen molecule.

Under standard conditions, which should be understood as pH 7.4, oxygen partial pressure of 40 mmHg, and temperature of 37 ° C, the low P ₅₀ of an adult male is 27 mm Hg or 3.6 kPa.

What factors can affect the affinity of hemoglobin for oxygen?

The affinity for oxygen of hemoglobin contained in erythrocytes may decrease in the presence of 2,3 diphosphoglycerate (2-3DPG), carbon dioxide (CO ₂), high concentrations of protons, or due to increased temperature; and the same is true for carbon monoxide (CO).

Functional implications

Carbon monoxide is able to interfere with the oxygen transport function in arterial blood. This molecule is capable of binding to hemoglobin and forming carboxyhemoglobin. This is because it has an affinity for hemoglobin about 250 times greater than O ₂, so it is capable of displacing it even when it is bound to it.

The body produces carbon monoxide permanently, although in small amounts. This colorless, odorless gas binds to the heme group in the same way that O _{2 does,} and normally about 1% of hemoglobin in the blood exists as carboxyhemoglobin.

Since the incomplete combustion of organic matter produces CO, the proportion of carboxyhemoglobin in smokers is much higher, reaching values ​​between 5 and 15% of total hemoglobin. Chronic increase in carboxyhemoglobin concentration is harmful to health.

An increase in the amount of CO that is inhaled that generates more than 40% carboxyhemoglobin is life threatening. When the ferrous iron binding site is occupied by CO, O ₂ cannot bind.

Binding of CO causes the transition of hemoglobin to the R structure, such that hemoglobin further reduces the ability to deliver O ₂ in blood capillaries.

Carboxyhemoglobin has a light red color. Thus, CO-poisoned patients turn pink, even in a coma and respiratory paralysis. The best treatment to try to save the lives of these patients is to have them inhale pure oxygen, even hyperbaric, to try to displace the binding of iron with CO.

References

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