CH4 | Protein Function (PT1)

Question 1

What is a ligand in the context of protein function?

Answer 1

A molecule that binds reversibly to a protein.

Question 2

What are some examples of molecules that can act as ligands?

Answer 2

Other proteins, enzyme substrates, or allosteric modulators.

Question 3

What is a protein’s binding site, and what is the role of the binding site in terms of binding a ligand?

Answer 3

A specific region on a protein where a ligand binds with specificity.

Question 4

How does a ligand interact with a protein’s binding site?

Answer 4

The ligand is complementary to the binding site in terms of size, shape, charge, and hydrophobic/hydrophilic character.

Question 5

What is the “induced fit” hypothesis in protein-ligand binding?

Answer 5

It’s the concept that the binding of a ligand often induces a conformational change in the protein.

Question 6

What is the result of the conformational change described in the induced fit hypothesis?

Answer 6

The conformational change makes the binding site more complementary to the ligand, allowing for tighter binding.

Question 7

What is the name given to the structural adaptation between a protein and a ligand during induced fit?

Answer 7

Induced fit.

Question 8

What is a hemoprotein?

Answer 8

A group of specialized proteins that contain heme as a tightly bound prosthetic group.

Question 9

What is a defining characteristic of a prosthetic group, as seen in hemoproteins?

Answer 9

A prosthetic group, as exemplified by heme in a hemoprotein, is a non-protein compound that is permanently associated with a protein.

Question 10

What type of compound is heme in the context of hemoproteins?

Answer 10

A prosthetic group.

Question 11

What is a common characteristic of both hemoglobin and myoglobin in terms of their structure?

Answer 11

Both are heme-containing proteins.

Question 12

What is the functional similarity between Hb and Mb?

Answer 12

Both are oxygen-binding proteins.

Question 13

Where is hemoglobin (Hb) found in the body?

Answer 13

In the blood, specifically in erythrocytes (red blood cells).

Question 14

Where is myoglobin (Mb) found?

Answer 14

In muscles, specifically in myocytes (muscle cells).

Question 15

What are the two main components of a heme molecule?

Answer 15

Protoporphyrin ring IX and a central iron atom in the ferrous (Fe+2) state.

Question 16

How many coordination bonds does the ferrous ion have in a heme, and what are they with?

Answer 16

Six. Four with nitrogen atoms of the porphyrin ring, one with an imidazole ring of a histidine (proximal histidine), and one with oxygen.

Question 17

What is the oxidation state of iron required for heme to bind oxygen, and what happens if it changes?

Answer 17

It must be in the reduced ferrous (Fe+2) state. If it’s in the ferric (Fe+3) state, it cannot bind oxygen.

Question 18

How many oxygen molecules (O2) can a single heme molecule bind?

Answer 18

One.

Question 19

What is a visible characteristic of heme in blood and muscles?

Answer 19

It’s a red pigment, giving them their red color.

Question 20

What is the quaternary structure of hemoglobin (Hb)?

Answer 20

It’s a heterotetramer, meaning it consists of four different polypeptide subunits.

Question 21

What is each subunit of Hb composed of?

Answer 21

A “globin” protein bound to a “heme” group.

Question 22

How many oxygen molecules (O2) can one Hb molecule bind, and why?

Answer 22

Four. Each subunit binds one O2 molecule.

Question 23

What are the four types of human Hb found in adults?

Answer 23

A, F, A2, and A1c.

Question 24

Which is the predominant type of Hb in adults, and what is its subunit composition?

Answer 24

HbA. It has two alpha (α) and two beta (β) chains.

Question 25

How are the Hb chains organized, and what characterizes the interaction between these organizations?

Answer 25

They are organized as two dimers (αβ-1 and αβ-2). The interaction between the dimers is non-covalent (weak).

Question 26

How does the binding of oxygen affect the conformation of the Hb dimers?

Answer 26

The dimers can move in response to O2 binding, resulting in two conformational states based on the presence or absence of O2.

Question 27

What are the two main conformational states of hemoglobin (Hb)?

Answer 27

The T-state (taut) and the R-state (relaxed).

Question 28

Which state of Hb is associated with low oxygen affinity, and what is another name for this state?

Answer 28

The T-state (deoxyhemoglobin).

Question 29

When is the T-state of Hb predominant, and what does it facilitate?

Answer 29

At low PO2 (in tissues), facilitating oxygen release.

Question 30

Which state of Hb is associated with high oxygen affinity, and what is another name for this state?

Answer 30

The R-state (oxyhemoglobin)

Question 31

When is the R-state of Hb predominant, and what does it facilitate?

Answer 31

At high PO2 (in the lungs), facilitating oxygen uptake.

Question 32

What characterizes the interaction between the αβ-dimers in the T-state of Hb?

Answer 32

They are constrained by a network of ionic and hydrogen bonds.

Question 33

How does the binding of O2 affect the αβ-dimers in the R-state of Hb?

Answer 33

It causes the rupture of some ionic and hydrogen bonds between the dimers, allowing more freedom of movement.

Question 34

What is the relationship between hemoglobin subunits and heme groups in terms of oxygen binding?

Answer 34

Each hemoglobin subunit is bound to a heme group, and each heme group can bind one O2 molecule.

Question 35

How does the structure of hemoglobin relate to its ability to bind multiple oxygen molecules?

Answer 35

Each hemoglobin molecule has four subunits, each with a heme. Therefore, each hemoglobin can bind four O2 molecules.

Question 36

Trace the path of oxygen binding in hemoglobin, starting from red blood cells.

Answer 36

Red blood cells (RBCs) contain hemoglobin (Hb), which contains a heme prosthetic group. Heme contains a ferrous (Fe2+) ion, which binds to oxygen (O2).

Question 37

What type of protein is myoglobin, and what is its primary function?

Answer 37

It's a heme-containing globular protein that binds oxygen.

Question 38

Where is myoglobin found in the body?

Answer 38

Exclusively in muscle tissue (myocytes) and heart tissue (cardiomyocytes).

Question 39

What gives myoglobin its characteristic color, and what is the significance of this color?

Answer 39

The heme in myoglobin gives it a red pigment, contributing to the red color of muscle.

Question 40

How many subunits does myoglobin have, and how does this relate to its function?

Answer 40

Myoglobin has only one subunit (monomeric) and therefore can bind only one molecule of oxygen.

Question 41

What is the structure of the myoglobin subunit, and how does it relate to hemoglobin?

Answer 41

The subunit is a "globin" protein with 8 alpha-helices, and it resembles the β-chain of hemoglobin.

Question 42

What is an oxygen dissociation curve, and what does it represent for Hb and Mb?

Answer 42

A graphical representation showing the relationship between the amount of oxygen bound to Hb or Mb and the partial pressure of oxygen.

Question 43

What is the shape of the oxygen dissociation curve for Hb, and what does this indicate about its sensitivity to oxygen?

Answer 43

Sigmoidal. Hb is more sensitive to small changes in O2 concentration.

Question 44

What is the shape of the oxygen dissociation curve for Mb, and what does this indicate about its sensitivity to oxygen?

Answer 44

Hyperbolic. Mb is less sensitive to changes in O2 concentration compared to Hb.

Question 45

How does the oxygen affinity of Hb compare to Mb, and how does this affect their function?

Answer 45

Hb has a lower affinity for oxygen, allowing it to release oxygen more easily, making it an oxygen transporter.

Question 46

How does the oxygen affinity of Mb compare to Hb, and how does this affect their function?

Answer 46

Mb has a higher affinity for oxygen, binding it strongly and making it an oxygen storage protein.

Question 47

Based on their oxygen dissociation curves, where is Hb's function optimized, and where is Mb's function optimized?

Answer 47

Hb is optimized for oxygen delivery in the tissues (steeper part of the curve), while Mb is optimized for oxygen storage in muscles.

Question 48

What characteristic of Hb's oxygen dissociation curve is explained by cooperativity?

Answer 48

The sigmoidal shape of the curve.

Question 49

What is cooperativity in the context of Hb-oxygen binding?

Answer 49

The phenomenon where the affinity of Hb for O2 increases as more O2 molecules bind to its subunits.

Question 50

How does the binding affinity of the first oxygen molecule to deoxyhemoglobin compare to subsequent oxygen molecules, and why?

Answer 50

The first O2 binds weakly (difficult binding) because it binds to a subunit in the T-state.

Question 51

What facilitates the higher binding affinity of the subsequent oxygen molecules to Hb?

Answer 51

A conformational change to the R-form.

Question 52

How much greater is the affinity of Hb for the last oxygen bound compared to the first?

Answer 52

Approximately 300 times greater.

Question 53

When comparing Hb and Mb at the same partial pressure of oxygen (PO2), which one will have a higher saturation level, and what does this imply?

Answer 53

Mb will be more saturated at the same PO2. This indicates that Mb has a higher affinity for oxygen than Hb.

Question 54

How does Mb's affinity for O2 change across different oxygen concentrations, and how is this reflected in its dissociation curve?

Answer 54

Mb's affinity for O2 doesn't change much. This is reflected in its hyperbolic curve, which shows high saturation even at low PO2.

Question 55

In tissues, should Hb have a high or low affinity for O2? Why, and how is this reflected in the curve?

Answer 55

In tissues, Hb should have a low affinity for O2 to facilitate oxygen release. This is shown by the lower part of the sigmoidal curve where saturation drops significantly with decreasing PO2.

Question 56

In the lungs, should Hb have a high or low affinity for O2? Why, and how is this reflected in the curve?

Answer 56

In the lungs, Hb should have a high affinity for O2 to facilitate oxygen loading. This is seen in the upper part of the sigmoidal curve, where saturation is high even with small increases in PO2.

Question 57

What aspect of Hb's oxygen binding contributes to the sigmoidal shape of its dissociation curve? Briefly explain this aspect.

Answer 57

The cooperativity effect. As each oxygen molecule binds to Hb, the affinity for the next oxygen molecule increases, causing the steep rise in the curve.

Question 58

What does the sigmoid oxygen binding curve of hemoglobin represent in terms of its affinity states?

Answer 58

A transition between a low-affinity state and a high-affinity state.

Question 59

How does hemoglobin's conformation change as it transports oxygen between lungs and tissues?

Answer 59

It alternates between the low-affinity (T-state) and high-affinity (R-state) conformations.

Question 60

What characterizes an efficient O2 transport protein in terms of its binding and release behavior?

Answer 60

It should bind O2 efficiently at high PO2 (like in the lungs) and release it at low PO2 (like in the tissues).

Question 61

In the context of the sigmoid curve, what do the flat upper and lower portions of the curve signify?

Answer 61

The upper flat portion signifies the high-affinity state (lungs - loading O2), and the lower flat portion signifies the low-affinity state (tissues - unloading O2).