Module 5

Question 1

Ligands

Answer 1

Many proteins undergo reversible interactions with other molecules
These interactions can serve to regulate protein function
A molecule reversibly bound by the molecule is called a ligand
A ligand can be any molecule including another protein

Question 2

How do Ligands bind

Answer 2

A ligand binds at a specific site on the protein called a binding site
The binding site is usually complementary to the ligand in terms of shape, charge, hydrophobicity, and hydrogen bonding potential
A given protein may have multiple binding sites for multiple ligands `

Question 3

Induced fit

Answer 3

The binding of a ligand may cause a conformational change in the protein
This induced fit can change the properties of the protein
These changes in protein in structure often relate to changes in function

Question 4

obstacles of Oxygen Delivery and Storage

Answer 4

Solubility of oxygen is too low to meet passive diffusion
Amino Acid side chains not well suites for reversible binding of oxygen
Transition state metals have strong tendency to bind oxygen but produce damaging free radicals

Question 5

Myoglobin

Answer 5

Monomeric protein that facilitates oxygen storage in peripheral tissue

Question 6

Hemoglobin

Answer 6

Tetrameric protein found in red blood cells that transports oxygen from lungs to the periphery

Question 7

Oxygen

Answer 7

As a limiting resource
Poorly soluble in aqueous solutions
Emergence of larger multicellular organisms depended on the evolution of proteins that could transport and store oxygen
Amount of available oxygen which can be delivered within the organism can limit its size

Question 8

Heme Prosthetic Groups

Answer 8

Cellular iron is bound in forms that sequester it and make it less effective
Heme groups consists of a proroporphyrin ring system bond to a single Fe iron atom
Fe2+ binds O2 Fe3+ does not.

Question 9

The ring system

Answer 9

Provides four coordinating interactions with the iron atom
Myoglobin and Hemoglobin both use heme
Heme is bound with discrete pockets of myoglobin and hemoglobin

Question 10

Fe2+ 6 interactions

Answer 10

Four come from interactions with heme
Fifith comes from interaction with an imidazole group of a proximal histidine residue
The Sixth position is for 02 binding

Question 11

Distal Histidine

Answer 11

provides a stabilizing interaction for bound 02

Question 12

Myoglobin Structure

Answer 12

Single sub unit is an example of Tertiary structure
With a single heme group, myoglobin can bind one oxygen molecule

Question 13

Hemoglobin Structure

Answer 13

4 sub units is an example pf quaternary structure
Each subunit of hemoglobin closely resembles myoglobin

Question 14

Oxygen binding of Myoglobin

Answer 14

Has a higher affinity for oxygen
Myoglobin has a hyperbolic curve

Question 15

Oxygen binding of hemoglobin

Answer 15

Has less affinity for oxygen compared to myoglobin
Displays sigmoidal behaviour
Indicating copperativity

Question 16

Myoglobin Oxygen Saturation Curve

Answer 16

The oxygen saturation curve of myoglobin is hyperbolic, indicating a single O2 binding constant
Amount of O2 requires to half saturate the protein is quantified by P50

Question 17

P50 OF MYOGLOBIN

Answer 17

3 Torr

Question 18

Saturation calculation

Answer 18

pO2/pO2 + P50

Question 19

oxygen Transport of Hemoglobin

Answer 19

Hemoglobin is contained in red blood cells
It is a Quaternary Structure
Hemoglobin is an allosteric protein whose oxygen affinity is regulates through various physiological signals

Question 20

Allosteric Proteins

Answer 20

Allosteric proteins have T (Inactive) and R (active) forms
T and R are always in rapid equilibrium

Question 21

Allosteric proteins binding to Oxygen

Answer 21

A protein that binds O2 with high and constant affinity would saturate effectively with O2 in lungs but not release it to the tissue
A protein with lower O2 affinity would be able to release oxygen to the tissues but would not have sufficient affinity to saturate in the lungs

Question 22

Allosteric Modulators

Answer 22

Bind allosteric proteins at specific sites
Can be either activators or inhibitors

Question 23

Allosteric Activators

Answer 23

Stablize R state

Question 24

Allosteric Inhibitors

Answer 24

Stabilize T state

Question 25

Homotropic

Answer 25

When ligand and modulator are the same

Question 26

Heterotropic

Answer 26

When modulator is different than ligand

Question 27

Binding of O2 in Hemoglobin

Answer 27

The binding and release of O2 from hemoglobin are allosterically regulated
O2 is a homotrpic allosteric activator for hemoglobin
Binding the first oxygen by hemoglobin causes a conformational change making it easier to bind subsequent 02 (Positive Cooperativity)

Question 28

O2 Stabilization

Answer 28

O2 binding stabilizes the R state of hemoglobin which has higher O2 affinity than the T state

Question 29

Iron during R and T state

Answer 29

With T state hemoglobin iron atom is outside the plane of the heme ring
With Transition to R state (Oxygen bound) iron moves to the plane of the ring
The minor movement within one subunit causes structural changes that are translated to the Quaternary Structure of the protein

Question 30

Oxygen Saturation Curve of Hemoglobin

Answer 30

At partial pressured of oxygen found in the lungs, Hb completely saturates O2
At Partial pressures of oxygen found in the periphery, Hb releases over half of its O2 load.
P50 of hemoglobin closely matches the partial pressures of O2 found in the periphery

Question 31

2, 3 BPG

Answer 31

2, 3 BPG is a heterotrophic allosteric Inhibitor
Decreases hemoglobins affinity for oxygen
2, 3 BPG carries 5 units of negative charge
The pocket formed at the interface between the subunits of deoxyhemoglobin contains 5 positivelt charged residues
This pocket is unique to deoxyhemoglobin

Question 32

Fetal Hemoglobin

Answer 32

A fetus breathes in the womb by stripping O2 away from maternal blood.
Fetal Hb has a higher oxygen affinity than adult Hb
Adult Hb has six + residues at 2, 3 BPG binding site, fetal Hb has four
Histidine is related by serine
Decreased affinity for 2, 3 BPG translates into higher O2 affinity for fetal Hb

Question 33

Low Allosteric Inhibitor

Answer 33

Higher Affinity for Oxygen

Question 34

High Altitude

Answer 34

There is less O2 in high altitude
Adaptation to high altitude can rapidly occur through increased BPG
Increased BPG decreases Hemoglobins affinity for oxygen to ensure sufficient O2 delivery in the periphery

Question 35

Bohr Effect

Answer 35

Describes pH dependence of Hemoglobins affinity for oxygen

Question 36

Decreased pH

Answer 36

Hemoglobin has lower affinity for Oxygen

Question 37

Active tissues have lower pH

Answer 37

because increased muscle activity increases production of CO2. CO2 decreases pH
In extreme exercise muscles produce lactic acid to further decrease pH

Question 38

Two challenges of cellular respiration

Answer 38

Delivering sufficient O2 to tissues
Removing CO2 from the periphery

Question 39

Mechanism 1

Answer 39

CO2 is taken up by red blood cells and converted to bicarbonate and a proton by the enzyme carbonic anhydrase
it converts CO2 into a soluble form for transport to the lungs
The decreased pH decreases hemoglobins O2 affinity to promote O2 release to active tissues

Question 40

Mechanism 2

Answer 40

CO2 can form a covalent carbamate linkage to the N terminus of each chain of hemoglobin to form carbminoheloglobin

Reaction does
Coverts CO2 into a more soluble form to assist in its transport to lungs
Carbamino hemoglobin has low 02 affinity to promote O2 release
The released proton promotes O2 release through the Bone effect