Terms in this set (60)
The process which provides the major source of ATP in aerobic organisms
Oxygen Delivering Mechanism
1. Development of a circulatory system. This delivers oxygen to cells and ensures that there is oxygen in tissues in large animals
2. Acquisition o oxygen carrying proteins such as myoglobin and hemoglobin. This helps overcome the limitation of low solubility in water
The oxygen binding molecule that is found in muscle.
This serves as a reserve supply of oxygen and facilitates the movement of oxygen within the muscle.
The oxygen binding molecule that greatly increases the oxygen transporting capacity of blood.
It also plays a critical role in the transport of CO2 and hydrogen ions in blood
2nd tertiary structure that was determined (from horse)
First protein whose tertiary structure was determined (via X-ray crystallography).
It was determined by JOHN KENDREW. It was obtained from the skeletal muscle of sperm whales
Heme prosthetic group
Ability of myoglobin and hemoglobin to bind to oxygen depends on the presence of this group.
Nonprotein components that are tightly bound to many proteins and contribute to their biological activity.
A protein without its prosthetic group is known as APOPROTEIN
A protein without without its prosthetic group
Consists of an organic part (porphyrin ring) and an iron atom
Protoporphyrin IX + Fe !!!
Requires the myoglobulin/hemoglobulin protein in order to bind to oxygen.When it is not bond to myoglobin/hemogloblin protein, the iron will be oxidized into its ferric states.
Iron cannot be bound to oxygen in its ferric state.
Protoporphyrin IX + Fe
Four PYRROLE RINGS are linked by bridging groups to form a PLANAR PORPHYRIN RING aka TETRA PORPHYRIN RING.
Is the PROSTHETIC GROUP to myoglobin as well as hemoglobin
Fe^3+ cannot bind oxygen
Only ferrous (Fe^2+) can bind to oxygen
Fe^2+ can bind to oxygen. It is the only form of iron that can bind to oxygen
Can form up to 6 bonds
Will form four bonds to nitrogen in the center of the protoporphyrin ring. The fifth and sixth bond are on opposite sides of this plane
A classic example of a globular protein. It is extremely compact with 153 amino acids.
Contains 8 ALPHA HELICAL SEGMENTS and 5 NON-HELICAL SEGMENTS
Helical segments are referred to as REGIONS A-H (First residue in helix A is called A1, second is called A2)
Non-helical segments separate the helical segments (referred to as segment AB, BC, etc...)
The interior of this molecule contains almost all nonpolar amino acids with the exception of two histidine residues.
The histidine resides actually interact with the heme group and oxygen.
Exterior of this structure contains both nonpolar and polar amino acids.
HAS NO DISULFIDE BONDS
Heme group is located in a hydrophobic pocket of the molecule. It is held in place by HYDROPHOBIC INTERACTIONS between the heme and the non-polar R groups of protein.
Without the heme group, the protein is not as tightly folded. So the heme has influence on the structure of this substance.
Myoglobin Oxygen Binding Site
Iron atom in heme can form 6 hydrogen bonds. 4 of these bonds will be binded to the nitrogen of the pyrrole rings of heme. These bonds will be one the same plane as the polyporphyrin ring.
The fifth bond (fifth coordination position of Fe) will be occupied by one of the N atoms of the imidazole side chain of HisF8.
The sixth bond will be bonded to oxygen (on the sixth coordination plane)
Both coordination site will be one opposite side of the porphyrin ring.
The histidine molecule of myoglobin that binds to the fifth coordination plane of iron in the heme group.
The histidine group which functions as a gate that regulates entry of oxygen into the hydrophobic pocket to bind heme.
It sterically hinders oxygen from binding perpendicularly to the plane of heme. It forces oxygen and CO to bind to the Fe in heme at an angle.
If HisE7 was not present, CO would bind to heme at a higher affinity than oxygen. Since HisE7 sterically regulates the binding angle, it would lower heme's affinity for CO and increase heme's affinity for binding oxygen.
O2 binding angle
Critical for myoglobin function. Cannot be 90 degrees and is sterically hindered by HisE7.
Has the best affinity for oxygen at 120 degrees.
Prevents traces of CO produced through metabolism from occupying all of the oxygen binding sites on the hemes
A molecule that competes with oxygen for heme. Is sterically hindered by HisE7 of myoglobin/hemoglobin and will bind to heme at 120. At the angle, the affinity of heme for this substance is reduced
A poison that can block the binding of oxygen to myoglobin and more importantly to hemoglobin.
Blocks final step of the electron transport chain in the mitochondria to inhibit ATP production (binds to the Fe of the heme group in cytochrome c oxidase to block electron flow of oxygen)
Co is produced endogenously during the breakdown of heme into bilirubin. Levels of endogenously produced CO is such that about 1% of sites in myoglobin and hemoglobin are blocked by CO (tolerable to organisms)
Levels of CO bound to heme would be toxic if not for HEME ASSOCIATED PROTEINS that sterically impose a bend in the CO bond. Bent weakens the interactions of CO with heme and favors oxygen binding
Provides a reserve supply of oxygen and facilitates rapid diffusion of oxygen within the MUSCLE.
It is a muscle protein and contains one polypeptide bond
Carries oxygen in blood and consists of FOUR polypeptide chain (2 alpha, and 2 beta)
Also carries CO.
It is a TETRAMER with 2 identical ALPHA chains and 2 identical BETA chains.
Both the alpha chains and beta chains are similar length, amino acid sequence and tertiary structure to myoglobin
Alpha and Beta chains
Chains that make up the tetramer structure of hemoglonin.
Both of these chains are similar in length, amino acid sequence and tertiary structure to myoglobin.
However, less than half of the amino acids are identical between the alpha chain, the beta chain, and myoglobin.
All these proteins chains are HOMOLOGUS (derived from the same common ancestor)
A gene related to a second gene by descent from a common ancestral DNA sequence. Relationship between the genes may have been separated by the event of speciation or to the relationship between genes separated by the event of genetic duplication.
Example: human hemoglobin and myoglobin
Genes in different species that are evolved from a common ancestral gene by speciation. The genes retain the same function in the course of evolution.
Example: shark myglobin and human myoglobin
Genes related by duplication within a genome.
Genes evolve new functions but may still be related to the original one.
Example: human alpha globin gene and human beta globin gene
Hemoglobin oxygen binding
Binding of oxygen is regulated by specific molecules in the environment (H+, CO2, 2,3,-BPG)
Can bind up to four molecules of oxygen whereas myoglobin can only bind up to one molecule of oxygen
A protein that changes conformation to another when it binds another molecule or is covalently modified.
The conformational change alters the functional activity of the protein
Property that occurs when binding facilitate conformational changes in a molecule that enhances additional binding.
Binding of oxygen enhances additional binding of oxygen to the same hemoglobin molecule
Myoglobin does not exhibit this property
Hb Affinity for Oxygen
Is dependent on
-binding of CO2
-levels of 2,3-BPG
Mb binding to oxygen is not regulated by these components
The relationship of binding of oxygen to hemoglobin in the oxygen dissociation curve. Each oxygen molecule that that binds to hemoglobin facilitates binding of subsequent oxygen molecules
The relationship of binding oxygen to myoglobin in the oxygen dissociation curve. Mygolobin exhibits a steady increase in oxygen saturation
Depicts the differences in the oxygen binding affinity of hemoglobin and myoglobin when exposed to different factors.
pOxygen Effect on Myoglobin
For any given level of this, the saturation of oxygen binding sites is greater for myoglobin than for hemoglobin.
This is because myglobin has a higher affinity for oxygen than hemoglobin. This is why myoglobin can store oxygen in muscle even at very low partial pressures of oxygen
POxygen Effect on Hemoglobin
Hb is fully saturated with oxygen in the lungs (100 torrs) but releases not than half of its bound oxygen in the capillaries of active muscles and tissues where the partial pressure of oxygen is low (20 torr) and oxygen is really needed.
The partial pressure of oxygen that is needed for hemoglobin to release the oxygen to muscle and tissues.
At this partial pressure, hemoglobin is less than 50% saturated
Hb positive cooperativity
Binding of oxygen to one heme facilitates binding of oxygen to the other hemes of the same tetramer.
The unloading of hemes facilitates the the unloading of hemes at others.
Indicates that the positive cooperative binding of oxygen by hemoglobin enables it to deliver twice as much oxygen to tissues as it would be if the binding sites acted independently.
Oxygenated Hemoglobin Structure
The two beta chains are together in the oxygenated form than in the deoxygenated form.
The binding of an oxygen molecule in one subunit induces strain in another subunit and causes some noncovalent bonds to BREAK.
Hb exhibits different TRANSIENT conformation depending on the number of oxygen molecules bound (due to the ALLOSTERIC properties of hemoglobin)
Dexoygenated hemoglobin iron location
The iron atom is out of the plane of heme due to the steric repulsion between HisF8 and the nitrogen atoms of the porphyrin ring.
Once oxygenated, the iron atom moves into the plane of porphyrin ring
Oxygenated hemoglobin iron location
The iron atom moves into the place of the porphyrin ring.
When deoxygenated, the iron atom of hemoglobin is out of the plane due to steric replusions between HisF8 and nitrogen atoms.
Movement of the iron atom and HisF8 is TRANSMITTED to other hemoglobin subunits through their intimate interactions with many neighboring amino acid side chains.
Hemoglobin Structure Regulating Factors
pH (H+ concentration)
Binding of 2,3-bisphosphoglycerate
In contrast, myoglobin does not change oxygen binding conformation over a large range of pH or CO2 concentration and does not bind 2,3-BPG.
pH Effect on Hemoglobin Oxygen Affinity
Acidity enhance the release of oxygen (low pH, high H concentration). Increase acidity will lower hemoglobin's affinity for oxygen.
High pH shifts the curve to the left and low pH shifts the curve to the right.
Affinity of oxygen for myoglobin is not affect by pH within physiological range
CO2 Effect on Hemoglobin Oxygen Affinity
Increasing the concentration of CO2 (at constant pH) will lower the affinity of hemoglobin for oxygen.
Will shift the right.
In rapidly metabolizing tissues (contracting muscle), high levels of CO2 and H+ are generated. This will cause hemoglobin's affinity for oxygen to lower. By doing this, hemoglobin will release more oxygen to the surrounding metabolizing tissue (MEETING METABOLIC NEEDS).
The reciprocal effect occurs in the lungs. High concentration of O2 in lungs forces unloading of H+ and CO2.
Noncovalent electrostatic interactions between oppositely charged amino acid side chains.
Deoxygenated Hemoglobin Salt Bridges
The deoxygenated form of hemoglobin contains 8 SALT BRIDGES that are broken upon binding oxygen. These salt bridges make deoxy Hb a tauter, more constrained molecule than oxyHB.
Deoxygenated form of hemoglobin
Oxygenated form of hemoglobin.
Breaking Salt Bridges
The number of salt links that need to be broken for binding an oxygen molecule depends on whether it is the first, second, third or fourth one to be bound.
More salt links are broken to permit binding of first oxygen than subsequent oxygen molecules. This requires more energy and is the results in the SIGMOIDAL shape of hemoglobin.
The histidine residue on hemoglobin. This histidine residue on the beta chain of hemoglobin is a key amino acid involved in the BOHR EFFECT.
At lower pH this is protonated and forms a salt bridge with ASP94 of the same chain.
This favors the conformation of DEOXY HB and thus the release of oxygen at lower pH (metabolically active tissue)
CO2 Mechanism of Lowering Oxygen Affinity
When present at high concentrations, CO2 can bombind with the free alpha amino groups of the hemoglobinchains to form CARBAMATE.
These are negatively charged ions that help stabilize the T form (which favors oxygen release in metabolically active cells)
Negatively charged ions that are formed when CO2 bonds to the free alpha amino groups of the hemoglobin chains.
Can stabilize the T form of deoxygenated Hb and will result in the release of oxygen in metabolically active tissue.
A third substance in the blood that is responsible for affecting hemoglobin's affinity for oxygen. Hemoglobins affinity for oxygen is lower in serum than in free solution.
LOWERS THE OXYGEN AFFINITY of hemoglobin BY A FACTOR OF 26!!!
It is present in human erythrocytes in about the same molar concentration as hemoglobin.
2,3-BPG Binding to Hemoglobin
2,3-BPG only binds to deoxyHb and not to oxyHb and occupies the central cavity of deoxyHb. Prevents the rebinding of oxygen once oxygen is released.
It stabilizes the deoxyHb quaternary structure by cross-linking beta chains by making more salt bridge (which will be broken upon oxygenation ONLY)
Binding of BPG and oxygen are MUTUALLY EXCLUSIVE. The central cavity cannot hold both BPG and oxygen at once.
Fetal hemoglobin has a higher affinity for oxygen than maternal (adult) hemoglobin.
So at any given pO2, HbF is more saturated with oxygen than adult Hb. This optimizes the transfer of hemoglobin from mother to fetus.
Globulin chains in HbF that replaces the two beta chains.
This makes the composition of the quaternary structure alpha2gamma2.
These chains form fewer salt bridges to BPG than the beta chains. Thus HbF binds BPG less strongly than does adult Hb and has a higher affinity to oxygen
Molecule is synthesized in a shunted pathway from glycolysis from 1,3-bisphosphoglycerate. Usually 1,3-BPG is synthesized into 3 phosphoglycerate in glycolysis
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