This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.
This paper seeks to explain the interaction between oxygen and carbonic acid in the blood by means of the acid-base equilibrium theory. It is hypothesised that oxygen absorption by blood depends upon a chemical combination between oxygen and haemoglobin.
Data from relevant investigations of pioneer researchers - Barcroft, Bohr, Christiansen, Douglas, Haldane and Hasselbach - were visited. The mass law equation was used in calculating values. These values gave an estimate of the probable effect that carbonic acid exerts upon the affinity of haemoglobin for oxygen. It became evident that haemoglobin and carbonic acid are not the only substances involved in the equilibrium reaction. The fluctuation in the calculated values was far from sufficient to account for the variation of bicarbonate with the varying hydrogen ion. It is assumed that there might be acid or base radicals present in the protein portion of the haemoglobin molecule that could be involved in this equilibrium reaction.
It is inferred that the influence of carbonic acid on the equilibrium between oxygen and haemoglobin may depend upon a chemical reaction involving the protein portion of the haemoglobin molecule that combines with carbonic acid. The union of carbonic acid with haemoglobin is uninfluenced by the presence of oxygen. Further investigation into this process is warranted.
Explanation of the Chemistry
Blood is a liquid transport system where important substances that are vital in sustaining life are carried around inside the human body. Of the many substances, this section will focus on the substances involved in the equilibrium between oxygen and carbonic acid in the blood. These substances are as follows:
The discussion that follows would also demonstrate the role of an acid-base reaction.
Red blood cells collect oxygen in the lungs and distribute it through arteries into the tissues.
Oxygen (O2) is transported in the blood in two ways (Donahoe):
in physical solution in the plasma as dissolved oxygen
in chemical combination with haemoglobin (HbO2) which is the major form of oxygen transport in the blood
According to Matthews et al (2000), the concentration of oxygen in the human lungs is high and this leads to the elevation of the partial pressure of oxygen. They also stated that the amount of carbon dioxide in the lungs is low and the transport of carbon dioxide towards the lungs leads to an acidic state causing the pH to rise. Figure 1 shows the combination of these chemical conditions that leads to oxygen attaching itself to haemoglobin forming oxyhaemoglobin (Kimball). Haemoglobin has iron ions attached to its complex proteins so as to produce oxygen-binding sites (Matthews et al).
When the concentration of oxygen becomes low as what happens inside a human cell, the oxyhaemoglobin breaks down to haemoglobin and oxygen (Kimball). The oxygen is then released inside the cell.
Figure 1- Haemoglobin: Oxyhaemoglobin Reaction
(Diagram courtesy of J. Kimball and available at http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/Blood.html#oxygen)
The Haldane effect describes the effect of oxygen on the ability of haemoglobin to combine with carbon dioxide. That is, deoxygenated haemoglobin (haemoglobin with no oxygen) has a greater ability to bind with carbon dioxide compared to oxyhaemoglobin. This enhances the ability of haemoglobin to take up carbon dioxide from the tissues and to be released in the lungs (Donahoe).
Carbon dioxide (CO2 ) is a product of the gas exchange process that occurs in the lungs. It is also a product of human cell metabolism. Its high concentration inside each cell of the human body causes oxyhaemoglobin to release oxygen into the cells (Rhoades & Pflanzer).
Carbon dioxide is transported in the blood in three ways: dissolved, combined with water to form carbonic acid converting to bicarbonate and in the form of carbamino compounds (carbon dioxide and protein). In saying this, the carbon dioxide transport system is not limited by the amount of haemoglobin present compared with the oxygen transport system (Matthews et al).
Figure 2 shows that carbon dioxide reacts with water inside the red blood cell leading to the formation of carbonic acid. Carbonic acid (H2CO3) then breaks down into a hydrogen ion (H+) and bicarbonate ion (HCO3-) (Kimball).
This chemical reaction occurs inside the red blood cell in such an amazing speed that is made possible by the presence of a catalytic enzyme called carbonic anhydrase. This enzyme is not present in the blood plasma; therefore, the same chemical reaction would be very slow if it occurs outside the red blood cell (Rhoades & Pflanzer). Therefore, it can be said that majority of the carbon dioxide is carried inside the red blood cell. The resulting bicarbonate is the main mechanism in which carbon dioxide is transported in the blood (Matthews et al).
H2O + CO2 ïƒŸïƒ H2CO3 ïƒŸïƒ H+ + HCO3-
The hydrogen ion that is generated from the breakdown of carbonic acid leads to increased acidity which lowers the body pH (Matthews et al). Inside the body, there are buffers that counter act the effects of acids. A buffer is a solution of a weak acid and its salt that prevents marked changes in hydrogen ion concentration. Haemoglobin acts as a buffer and it plays a significant role in the equilibrium between oxygen and carbonic acid (Rhoades & Pflanzer). To balance this acidic environment, haemoglobin combines with or buffers the hydrogen ion so as to maintain a stable pH (Donahoe). Maintaining a stable blood pH is important in sustaining life (Rhoades & Pflanzer).
Figure 2 - Transport of Oxygen and Carbon Dioxide in the Red Blood Cell
(Diagram courtesy of Transport of Oxygen in the Blood and available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm)
In the lungs, the chemical reaction stated below is reversed. The bicarbonate is changed back into carbon dioxide which is breathed out through the lungs (Rhoades & Pflanzer).
H2O + CO2 ïƒŸïƒ H2CO3 ïƒŸïƒ H+ + HCO3-
Red blood cells contain an oxygen-carrying substance called haemoglobin (Hb). Haemoglobin functions efficiently to meet the demands of maintaining equilibrium between oxygen and carbonic acid in the blood (Matthews et al). Figure 3 shows haemoglobin as having 4 complex protein chains called polypeptides: 2 alpha chains that have 141 amino acids and 2 beta chains that hold 146 amino acids (Kimball). Each of this complex protein chain contains 1 heme molecule which equates to 4 heme molecules in1 haemoglobin. Each heme molecule has a ferrous ion that interacts with oxygen. Therefore, 1 haemoglobin molecule binds four oxygen molecules forming oxyhaemoglobin. One red blood cell contains 280 million molecules of haemoglobin (Matthews et al). Haemoglobin transports and releases these molecules of oxygen to each cell in the body. The process of transporting oxygen where oxygen binds with haemoglobin is a reversible reaction (King).
Hb + 4O2 ïƒŸïƒ Hb.4O2
In Figure 3 (see below), there are four rectangular plates with a central sphere. The rectangular plate represents the heme and the central sphere represents the ferrous ion. This rectangular plate-central sphere portion of the haemoglobin is the oxygen-binding site. The four coiled and elongated parts represent the complex protein chain called polypeptide (Transport of Oxygen in the Blood available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm).
Haemoglobin also binds carbon dioxide to a smaller degree leading to the formation of carbaminohaemoglobin (Transport of Oxygen in the Blood available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm).
An acidic environment facilitates oxygen release (Matthews et al). The carbon dioxide in the blood creates an acidic environment causing oxyhaemoglobin to release oxygen - this process is called the Bohr effect (Transport of Oxygen in the Blood available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm). The Bohr effect states that an increase in carbon dioxide in the blood will cause oxygen to be displaced from the oxyhaemoglobin thereby promoting oxygen release in tissues (Kimball).
Figure 2 shows that once carbon dioxide is released into the blood it enters the red blood cells where it reacts with water (Transport of Oxygen in the Blood available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm). The carbonic anhydrase enzyme speeds up the formation of carbonic acid and the following dynamic equilibrium is established (Rhoades & Pflanzer)
H2O + CO2 ïƒŸ--------------ïƒ H2CO3
Carbonic acid then breaks down releasing hydrogen ion and forming bicarbonate (Matthews et al). A dynamic equilibrium exists with all these chemicals and this chemical reaction is reversible (Transport of Oxygen in the Blood available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm)
H2CO3 ïƒŸïƒ H+ + HCO3-
Figure 3 - Structure of Haemoglobin
(Diagram courtesy of K. King available at http://www.docstoc.com/docs/14930487/Oxygen-Carbon-dioxide-Transport)
The breakdown of carbonic acid also releases hydrogen ion (see Figure 2) which interacts with oxyhaemoglobin and the resulting acidic environment causes the oxyhaemoglobin to release oxygen (Matthews et al). The release of oxygen reduces blood acidity. This reduced acidity allows carbon dioxide in the form of carbonic acid to be transported in the blood thus maintaining normal blood pH (Transport of Oxygen in the Blood available at http://www.rsc.org/education/teachers/learnnet/cfb/transport.htm).
Hb.4O2 + H+ ïƒŸïƒ HHb+ + 4O2
The chemical reaction and the gas exchange that occurs between oxygen and carbon dioxide is a continuous process (Rhoades & Pflanzer). Carbon dioxide breaks out from each cell of the body into the blood. It then reacts with oxyhaemoglobin which is rich with oxygen (Matthews et al). A chemical reaction occurs causing the oxyhaemoglobin to release oxygen and carries with it the carbon dioxide (King). Carbon dioxide is then carried up to the lungs where it gets released and the haemoglobin gets to combine with oxygen again (Rhoades & Pflanzer).
Though the article is dated (published 90 years ago), is there a way to prove its assumption (derived from the analysis of its secondary data) that there might be substances in the protein portion of the haemoglobin that could be involved in the equilibrium between O2 and CO2?
This question is justified because it shows the relationship of the dated journal article to current available facts.
From the analysis of its secondary data, the dated journal article assumed that there might be substances in the protein portion of the haemoglobin that could be involved in the equilibrium between O2 and CO2. In addition, the article also inferred that the influence of carbonic acid on the equilibrium between oxygen and haemoglobin may depend upon a chemical reaction involving the protein portion of the haemoglobin molecule that combines with carbonic acid.
As discussed under the section 'Explanation of the Chemistry', it was demonstrated that the protein portion of the haemoglobin does have a role to play in the equilibrium between O2 and CO2.
Under the section "Haemoglobin", I mentioned that haemoglobin binds carbon dioxide to a smaller degree leading to the formation of carbaminohaemoglobin (Transport of Oxygen in the Blood).
To further elaborate, the heme portion of the haemoglobin has N-terminal amino groups (see Figure 4).
Figure 4 - N-terminal Amino Group of the Heme
(Diagram courtesy of B. Lennert available at http://en.wikipedia.org/wiki/File:Heme.svg)
Carbon dioxide, as explained, is converted to bicarbonate. The bicarbonate then binds to the N-terminal amino groups of the heme to form carbamates (Matthews et al)
This carbamation reaction (see reaction below) provides the haemoglobin an additional means of transporting carbon dioxide from the cells of the body to the lungs (Matthews et al).
-NH3 + HCO3- ïƒŸïƒ -N-COO- + H+ + H2O
The hydrogen ion that is released from the binding of the bicarbonate to the N-terminal amino group lowers the pH which then promotes the release of oxygen. This process plays a part in achieving the Bohr effect whereby an environment that is acidic will facilitate the release of oxygen (Matthews et al).
The 1920 journal article's assumption and inference have now been proven by biochemistry studies of the late 20th century. Current facts confirm the presence of substances in the protein portion of the haemoglobin that is involved in the equilibrium between oxygen and haemoglobin. The substances that are specifically involved in the reaction are the N-terminal amino groups of the heme portion of the haemoglobin molecule (Matthews et al).
How does the biochemical internal environment of the red blood cell achieve equilibrium when the negative charged bicarbonate ion diffuses out of it?
This question is justified because it entails additional equilibrium reaction within the internal environment of the red blood cell.
As mentioned under the section "Explanation of Chemistry", the Bohr effect states that increase in carbon dioxide in the blood will cause oxygen to be displaced from the haemoglobin thereby promoting oxygen release in tissues (Kimball). Carbon dioxide enters the blood and reduces the blood pH causing oxygen to dissociate from Hb (Bohr effect). This then allows more carbon dioxide to bind to Hb. Hb + CO2 forms carbaminohaemoglobin (Transport of Oxygen in the Blood)
CO2 + HbNH2 ïƒŸïƒ HbNH2COOH
In addition to this minor CO2 transport mechanism, CO2 is also able to diffuse from the tissues to the red blood cells where it combines with H2O forming H2CO3 which then immediately dissociates to H+ + HCO3- (major CO2 transport mechanism) (Matthews et al). Hb immediately binds to H+ before it can leave the red blood cell and lowers the pH (Hb acts a buffer) (Donahoe). HCO3- diffuses into the red blood cell from the blood plasma and the intracellular Chloride (Cl-) breaks out of the red blood cell into the blood plasma. Vice-versa, the Cl- in the plasma enters back into the red blood cell once HCO3- is released. This exchange of one anion for another to balance the biochemical charge is to maintain the equilibrium within the red blood cell (King).
This Cl- - HCO3- exchange (called Chloride shift) again demonstrates the delicate equilibrium that occurs inside the human body. So next time you take your simple next breath, have in mind these complex equilibrium processes that occur inside your body in order for you to live.
This reminds me of Genesis 2:7b where it says "and God breathed into man's nostrils the breath of life; and man became a living soul" (King James).
Shouldn't the ferrous ion in the heme be oxidising once it combines with O2?
This question is justified because it makes one thinks that the ferrous ion should oxidise once oxygen binds to it; however, the outcome of this ferrous-oxygen binding is that the oxygen is not released readily.
Normally, if oxygen gets in contact with a ferrous (FeII) ion, the oxygen would oxidise the latter to the ferric (FeIII) state. It has been shown that heme dissolved in a solution outside the red blood cell would be easily oxidised rendering the oxygen-binding metal inactive where oxygen will not bind and instead a water molecule will occupy the oxygen-binding site (Matthews et al). In saying this, heme by itself does not protect the ferrous ion from being oxidised. According to Dickerson and Geis(1998), it is the hydrophobic (water inhibiting property) internal environment of the haemoglobin molecule that provides protection to the ferrous ion because a temporary rearrangement of electron occurs when the oxygen binds to the ferrous ion thus preventing it from being oxidised. The oxidation of iron is blocked maintaining its ferrous state and once the oxygen is released it is ready again to bind another oxygen molecule (Matthews et al).
Would a defective haemoglobin affect the equilibrium between O2 and CO2?
This question is justified because there are evidence that show abnormal haemoglobin exists in humans that are deleterious to life.
According to Dickerson and Geis (1998), there are abnormal haemoglobins inherent in humans and some of these abnormal haemoglobins are harmful to man.
Honig and Adams (1990) have shown that the harmful effects are due to the abnormality in the alpha and beta polypeptide chains where the abnormalities allow the oxidation process to continue in the haemoglobin molecule leading to unsuccessful binding of oxygen.
Therefore, individuals having abnormal haemoglobins would have difficulty transporting oxygen to the tissues (Rhoades & Pflanzer). In saying this, the equilibrium between O2 and CO2 will be compromised because of the ineffective oxygen transport leading to a decreased oxygen concentration in the body.