Hemoglobin

Amino Acids

Proteins are extremely large complex molecules. For instance, a very small protein can have as many as a thousand atoms. Luckily, proteins are composed of subunits called amino acids. There are only twenty different amino acids in which they all have the same basic structure, as follows

The Hydrogen bonded to the primary carbon is always Hydrogen. This is important for the polarity and hydrophobicity of the overall protein and in how a protein will eventually fold in on itself.

The term amino acid obviously comes from the amino functional group on the left and the carboxylic acid group on the right. It is noteworthy to state that the amino group is inherently a base and the carboxylic acid group is an acid, therefore, amino acids, and thus proteins, are both acids and bases. Molecules that are both acids and bases are known as being amphoteric and possess the quality of being buffers.

All twenty amino acids are the same except for the R group. The simplest R group is a Hydrogen and equates to the amino acid Glycine. The most complex amino acid would by Tryptophan where the R group is a complex Nitrogen-containing double ring structure known as an indole group.

The distinguishing R group imparts on the amino acid its physical and chemical properties. Some R groups are very polar and thus readily dissolve in water, others are nonpolar and thus hydrophobic. The hydrophobicity of the R group is important for it will determine the shape, function, and efficiency of the protein.

Proteins are formed by simply bonding the amino group of one amino acid to the carboxylic acid group of another amino acid in a dehydration reaction where water is given off.

Two amino acids bonded together are a dipeptide. Polypeptides are proteins or peptides with many amino acids. Most functional proteins require at least thirty amino acids in length. Insulin has 51 amino acids.

Proteins

Proteins are a class of biomolecules that perform two primary functions in all living cells. The first function is structural. Proteins form the structural basis of an organism. For instance, skin, bone, hair, and finger nails are pure forms of protein. Collagen is a sheet-like protein in your skin that keeps it tight and young looking. As we age the bonds in the collagen weaken and the face begins to age.

The second function of proteins is catalytic, or they aid in causing chemical reactions. Proteins that act as catalysts are called enzymes. Insulin is an enzyme that maintains the level of glucose in your blood stream. When the level or efficiency of this enzyme is abnormal, then diabetes is expressed.

Although extremely large and complex, a protein’s structure can be broken down into four stages of complexity. The first is the primary structure in which the exact amino acid length and linear sequence of amino acids determine the protein.

The secondary structure is the initial folding of the protein upon itself. The length and sequence of the primary structure along with the hydrophobicity of the R groups determine how the initially linear backbone of the protein will fold in on itself. The a-helix, the b-sheet, and the random coil form the three secondary configurations of folding and twisting. Essentially, hydrophilic R groups will face outward on the protein and hydrophobic R groups will form a tight inner core. This is due to the water environment of the cell in which proteins reside.

Tertiary structure occurs when certain R groups physically bond with other R groups. The primary bond would be a disulfide bride between the two sulfur containing amino acids, cysteine and methionine. These chemical bonds formalize the folding of the protein into a more rigid and permanent structure.

Quaternary structure will only occur when multiple polypeptide chains bond to form an even larger functional protein. Not all polypeptides require bonding to other peptides to be a functional protein.

The four stages of protein structure are shown below.

Myoglobin and Hemoglobin

Myoglobin and Hemoglobin are molecules that transport Oxygen from the lungs, upon inhalation, to the tissues through the blood stream. When the oxygen is released from the molecule, it then accepts Carbon dioxide waste from the cells, delivers it back to the lungs in which it is released upon exhalation. Myoglobin is usually found in lesser evolved animals, such as fish, and Hemoglobin is found in mammals and primates. Both are responsible for making blood the color red.

The cells use the Oxygen in cellular respiration to metabolize glucose and derive energy or ATP through the oxidation of that glucose. The six carbons in each glucose are oxidized to the point of producing Carbon dioxide, which is then considered waste by the cell and expelled. Myoglobin and Hemoglobin ensure that each of the cells in the organism have an ample supply of oxygen and properly remove the Carbon dioxide waste.

Myoglobin is the more simple of the two molecules. It primary structure consists of a single polypeptide chain of 153 amino acids in length, as shown

The secondary structure contains eight sublengths of a-helicies with a random coil between each a-helix.

where the above diagram is actually two different concept drawings of the same single Myoglobin molecule. Notice how the a-helicies and tight turns are similar between both renderings.

Anemia is the lack of red blood cells and more specifically a lack of Myoglobin or Hemoglobin in the blood to carry enough Oxygen to the cells or remove the CO₂ waste. Increasing the intake of Iron (Fe) will often stimulate the production of Myoglobin or Hemoglobin and thus increase the concentration of red blood cells in the stream. Iron is an integral and necessary part of the Myoglobin and Hemoglobin molecule. It forms the center of the heme group which is embedded in the center of the polypeptide chain, as shown above. The chemical structure of the heme is as follows

When Oxygen is bound to the Fe atom it causes the heme ring structure to pucker. This puckering causes the peptide portion of Myoglobin to break any bonds with the CO₂ waste the molecule is carrying back from the cells. The CO₂ is actually carried on the N-terminal end of the peptide, or at the end of the A a-helix in the above Myoglobin diagram. Therefore, Myoglobin and Hemoglobin not only act as a dual transport system, they do it efficiently because the molecules will never carry O₂ and CO₂ at the same time.

Hemoglobin performs the same job as Myoglobin. It is structurally a bit different then Myoglobin in that Hemoglobin requires four polypeptide chains to bond in a full quaternary structure. This four times more massive molecule is much more efficient at performing its duties then Myoglobin.

The primary structure of Hemoglobin is slightly modified to account for the larger more complex molecule. Two of the four Hemoglobin polypeptides are known as the a-chains, the other two are the b-chains. The a-chain is 141 amino acids in length and the b-chain is 146 amino acids long. The primary structure is shown below in which the identical regions are shown in red.

The secondary and quaternary structure can be seen in the following diagram

When we inhale, the blood in our lungs has a very high concentration of O₂. This high concentration of O₂ in the blood forces bonding of O₂ with the heme Fe atom. The puckering of the heme group occurs. Any CO₂ still bound to the N-terminal end of the polypeptide will be released from the molecule and then exhaled. Hemoglobin is more efficient then Myoglobin because after the first O₂ molecule bonds to the heme Fe atom in Hemoglobin, it not only induces the release of CO₂, but also sends a signal to the other three polypeptides. This chain reaction will stimulate them to bind much more easily to other free O₂ molecules. Myoglobin acts independently and does not have this interpeptide communication as does Hemoglobin, for it can work in concert as a massive four polypeptide molecule.

When the O₂-rich Hemoglobin arrives to an area with a very low concentration of O₂ and a high concentration of CO₂, the Hemoglobin is stimulated to release its O₂ cargo and bond to CO₂. The same interpeptide stimulation occurs, but in the reverse. Once the first O₂ molecules is released, it stimulates the other three to release O₂ that much easier and pickup CO₂.

References

Baum, S., Introduction to Organic and Biological Chemistry, 3^rd Edition, MacMillan Publishing Company, Inc., New York, (1982).

Darnell, J., Lodish, H., Baltimore, D., Molecular Cell Biology, Scientific American Books, New York, (1986).

Trefil, J., Hazen, R.M., The Sciences, An Integrated Approach, 3^rd Edition, John Wiley and Sons, Inc., New York, (2001).