Page 12 - Academic Press Encyclopedia of Physical Science and Technology 3rd Polymer

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Encyclopedia of Physical Science and Technology EN002C-64 May 19, 2001 20:39

216 Biopolymers

The details of the mechanism of action differ for each are held together by hydrophobic, ionic, and hydrogen
enzyme, but in each case a substrate is held by noncovalent bonding. Thus, hemoglobin molecules possess quaternary
forces at the enzyme surface. Amino acid side chains, structure, and changes in this quaternary structure are im-
and sometimes a coenzyme or metal ion, participate in portant in the uptake and release of oxygen.
transferring electrons, protons, or small functional groups Myoglobin, the storage protein, is required to have a
to or from the substrate to facilitate the reaction being high affinity for oxygen at the oxygen pressure of muscles.
catalyzed. Hemoglobin, on the other hand, must have more complex
Transport and storage of ions and small molecules is an- properties. The affinity for oxygen must be high at the
other function often performed by proteins. For example, oxygen pressure of the lungs and much lower in muscles
metal ions such as iron or potassium are transported with so that the oxygen can be passed on to the myoglobin.
the help of proteins. The transport and storage systems This change is brought about by relatively small changes
involved in the utilization of oxygen have been studied in tertiary and quaternary structure of the hemoglobin
intensively. In human blood, oxygen is carried round the molecules. The pH in muscles is usually slightly less than
body bound to a protein called hemoglobin; the oxygen is that in lungs, and this favors the deoxy form of hemoglobin
stored temporarily before use in tissues such as muscles over the oxy form. At this lower pH the side chains of cer-
by a related but less complex protein, myoglobin. tain amino acids are positively charged and are involved in
Both proteins are conjugated proteins (i.e., contain a interchain ionic bonding with negatively charged groups
nonprotein prosthetic group). This group is heme, a flat close by in the quaternary structure. In addition, the iron
organic ring system with an iron(II) ion at the center. This ion lies out of the plane of the heme ring system. On one
iron ion is normally surrounded by six atoms, each of side of the iron ion in both α-chains is a space capable
which donates a pair of electrons to the iron. These atoms of accommodating the oxygen molecule; in the β-chains
are four central nitrogens of the heme ring system, a ring this space is blocked by the side chain of an amino acid
nitrogen of a histidine residue (see Table I) of the polypep- residue. In lungs, when an oxygen molecule binds to the
tide chain and the oxygen of the oxygen molecule being heme of one α-chain, the iron ion moves back into the
transported. The heme group is colored, but uptake and plane of the heme ring, pulling part of the polypeptide
release of oxygen cause a color change. The oxy form chain with it. This in turn alters the position of one of
of hemoglobin is the bright red characteristic of arterial the helices of the chain, and the movement causes the
blood, while the deoxy form is the more purplish color breaking of some ionic and hydrogen bonds between an
seen in blood in veins. α- and a β-chain. A second oxygen can bind to a second
Myoglobin molecules consist of one polypeptide chain α-chain and bring about similar changes. With the break-
of about 150 amino acid residues and one heme group, ing of noncovalent bonds between the hemoglobin sub-
while hemoglobin has four polypeptide chains and four units, however, changes in quaternary structure can take
heme groups. In myoglobin, the chain is folded up to give place. The α- and β-chains rotate with respect to each
˚
the overall shape of a flattened sphere, and about 80% of other and the two β-heme groups move about 6 A closer
the amino acid residues are arranged in 8 α-helices. The to each other. The amino acid side groups of the β-chains
heme group is bound to the polypeptide chain by noncova- which blocked the oxygen-holding space now move away
lent bonds. The polypeptide chain is folded in such a way and oxygen can also bind to the hemes of the β-chains.
as to provide a hydrophobic pocket for the heme group, Further ionic bonds are broken and protons can be re-
and in fact the main purpose for the polypeptide chain of leased, a situation favored at the higher pH of the lungs.
myoglobin seems to be to provide a hydrophobic environ- In muscles the opposite changes take place. Although the
ment for the iron(II) of the heme. This prevents the iron(II) first oxygen molecule is given up with some difficulty,
from becoming readily oxidized to iron(III). Whereas the the release of the other three oxygen molecules becomes
iron(II) of myoglobin and hemoglobin can bind oxygen easier as changes in quaternary structure take place, chain
easily, iron(III) attached to the same proteins cannot. end ionic bonds are remade and the oxygen “pockets” of
The common form of hemoglobin consists of two pairs the β-chains become reblocked.
of identical chains, α-chains containing 141 amino acid Small molecules other than oxygen can also bind at
residues and β-chains of 146 amino acids. Each of the the heme groups. Unfortunately the affinity for carbon
four chains of hemoglobin is folded to provide a hy- monoxide is much higher than for oxygen, and so in an
drophobic pocket for the heme. Even though the pri- atmosphere containing carbon monoxide this molecule is
mary structures of hemoglobin and myoglobin differ, their bound preferentially. If the carbon monoxide level is high
chains are folded in a similar way. The four chains of enough, insufficient amounts of oxygen are transported
hemoglobin are not covalently linked to each other but from the lungs and death can ensue.