Structure of hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green

The structure of hemoglobin.

The evolution of oxygen carrying proteins represents a major adaptation in the history of life. Overcoming the low solubility of oxygen in water, oxygen carriers make aerobic respiration possible in tissues. The oxygen carriers in vertebrates are myoglobin and hemoglobin. Myoglobin is located in muscle. Hemoglobin serves as the oxygen carrier in blood, increasing its oxygen carrying capacity fifty fold.

The properties of oxygen carriers are worthy of extensive, dedicated focus in MCAT preparation, not only because topics such as the Bohr effect are long-standing favorites. The former was true in the days of the old MCAT and is even more true with the new, biochemistry focused MCAT. Additionally, the properties of hemoglobin are a model for how proteins behave. Hemoglobin provides a model for understanding how a comformational change may alter the pKa of a residue side-chain, for example, and it is the place to learn how cooperativity works in allosteric, multisubunit proteins, both important concepts to bring to enzyme mechanics and regulation.

WikiPremed Resources

Learning Goals

Proficiency 

Be able to apply the induced fit model in describing how substrate binding in the active site of an enzyme occurs.

Have a good sense of the mechanisms of enzyme activity as they relate to active site chemical structure as well as the roles of cofactors and coenzymes.

Understand how feedback regulation of enzyme catalysis occurs and the types of inhibition of enzyme activity.

Understand enzyme kinetics, especially the nomenclature and basic problem solving methods of the Michaelis-Menton model.

Understand how to describe the kinetic properties of allosteric enzymes.

Be able to point to a few specific examples demonstrating regulation of enzymes by covalent modification or proteolytic activation.

Suggested Assignments

Conceptual Vocabulary for Hemoglobin

Hemoglobin

Each list begins with basic conceptual vocabulary you need to know for MCAT questions and proceeds to advanced terms that might appear in context in MCAT passages. The terms are links to Wikipedia articles.
Respiration
Respiration is the movement of oxygen from the outside environment to the cells within tissues, and the removal of carbon dioxide in the opposite direction.
Fetal hemoglobin
Fetal hemoglobin is the main oxygen carrier protein in the human fetus.
Adult hemoglobin
Hemoglobin A (HbA), also known as adult hemoglobin, is the most common human hemoglobin tetramer, accounting for over 97% of the total red blood cell hemoglobin.
Metalloprotein
Metalloprotein is a generic term for a protein that contains a metal ion cofactor.
Heme
Heme is a coordination complex consisting of an iron ion coordinated to a porphyrin acting as a tetradentate ligand, and to one or two axial ligands.
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the skeletal muscle tissue of vertebrates in general and in almost all mammals.
Hypoxia
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level.
2,3-Bisphosphoglycerate
Present in human red blood cells at approximately 5 mmol/L. 2,3-Bisphosphoglycerate is a three-carbon isomer of the glycolytic intermediate 1,3-bisphosphoglyceric acid (1,3-BPG).
Oxygen–hemoglobin dissociation curve
The oxygen–hemoglobin dissociation curve is a curve that plots the proportion of hemoglobin in its saturated (oxygen-laden) form on the vertical axis against the prevailing oxygen tension on the horizontal axis.
Bohr effect
The Bohr effect is a phenomenon by which the oxygen binding affinity of hemoglobin is inversely related both to acidity and to the concentration of carbon dioxide.
Carbaminohemoglobin
Carbaminohemoglobin is a compound of hemoglobin and carbon dioxide, and is one of the forms in which carbon dioxide exists in the blood.
Hemeprotein
A hemeprotein is a protein that contains a heme prosthetic group.
Globins
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen.
Heterotetramer
A heterotetramer is a 4-subunit complex where one or more subunits differ.
Porphyrins
Porphyrins are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their alpha carbon atoms via methine bridges.
Superoxide
he reactive oxygen ion superoxide is particularly important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature.
Carboxyhemoglobin
Carboxyhemoglobin is a stable complex of carbon monoxide and hemoglobin (Hb) that forms in red blood cells upon contact with carbon monoxide (CO).
Haldane effect
The Haldane effect is a property of hemoglobin by which oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin which increases the removal of carbon dioxide.
Blood gas tension
Blood gas tension refers to the partial pressure of gases in blood.
Ferritin
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion.
Protomer
A protomer is the structural unit of an oligomeric protein. It is the smallest unit composed of at least two different protein chains that form a larger hetero-oligomer by association of two or more copies of this unit.
Methemoglobin
Methemoglobin is hemoglobin in the form of metalloprotein, in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin.
Biliverdin
Biliverdin is a green tetrapyrrolic bile pigment, and is a product of heme catabolism.
Bilirubin
Bilirubin is a yellow compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates.
Transferrins
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of Iron (Fe) through blood plasma.
Triplet oxygen
Triplet oxygen refers to the S = 1 electronic ground state of molecular oxygen (dioxygen). It is the most stable and common allotrope of oxygen.
Singlet oxygen
Singlet oxygen is a gaseous inorganic chemical with the formula O=O in which oxygen is in a quantum state where all electrons are spin paired.
Hematocrit
The hematocrit is the volume percentage (vol%) of red blood cells in blood, measured as part of a blood test.
Neuroglobin
Neuroglobin is a member of the vertebrate globin family involved in cellular oxygen homeostasis and reactive oxygen/nitrogen scavenging. It is an intracellular hemoprotein expressed in the central and peripheral nervous system, cerebrospinal fluid, retina and endocrine tissues.
Porphobilinogen
Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.
Cytochrome-b5 reductase
Cytochrome-b5 reductase is responsible for converting methemoglobin back to hemoglobin.
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