Allosterism and allosteric proteins Flashcards

1
Q

What is the activation energy of a reaction?

A

Activation energy is the energy required to initiate a chemical reaction by enabling reactants to reach the transition state.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is an endergonic reaction?

A

An endergonic reaction requires an input of energy to proceed, as the products have a higher energy level than the reactants. Example: Protein synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is an exergonic reaction?

A

An exergonic reaction releases energy as it proceeds, with reactants starting at a higher energy level than the products. Example: ATP hydrolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do enzymes affect activation energy?

A

Enzymes lower the activation energy required for a reaction to occur, making the reaction faster and more efficient without changing the overall energy released or absorbed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do enzymes lower activation energy?

A

Enzymes stabilize the transition state, align reactants in the correct orientation, or provide an alternative reaction pathway.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Do enzymes alter the overall energy released or absorbed in a reaction?

A

No, enzymes only lower the activation energy; they do not change the overall energy released or absorbed in the reaction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to reaction speed in the presence of an enzyme?

A

The reaction proceeds much faster due to the lower activation energy barrier provided by the enzyme.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why are enzymes important for biological systems?

A

Enzymes enable biochemical reactions to occur rapidly and efficiently under physiological conditions, such as normal body temperature and pH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What diseases are linked to enzyme dysfunction?

A

Metabolic disorders like phenylketonuria (enzyme mutation in phenylalanine metabolism) and liver dysfunction (elevated ALT/AST levels) can result from enzyme abnormalities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are enzymes used in medicine?

A

Enzymes are targeted in therapies (e.g., protease inhibitors for HIV, ACE inhibitors for hypertension) and used as diagnostic markers for diseases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the Bohr Effect?

A

The Bohr Effect describes how lowered pH (increased H⁺) and increased CO₂ reduce hemoglobin’s affinity for oxygen, promoting oxygen release to tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Who discovered the Bohr Effect, and when?

A

The Bohr Effect was discovered by Christian Bohr in 1904.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does CO₂ affect hemoglobin?

A

CO₂ is hydrated in tissues to form carbonic acid, which dissociates into H⁺ and bicarbonate. The increased H⁺ lowers pH, stabilizing the T-state of hemoglobin and reducing oxygen affinity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the T-state of hemoglobin, and how is it relevant?

A

The T-state (Tense state) of hemoglobin has a low affinity for oxygen. Increased H⁺ and CO₂ stabilize this state, promoting oxygen release to tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does CO₂ directly bind to hemoglobin?

A

CO₂ binds to the amino-terminal ends of hemoglobin’s globin chains, forming carbaminohemoglobin. This stabilizes the T-state and facilitates oxygen unloading.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens to hemoglobin in the lungs?

A

In the lungs, high oxygen levels promote oxygen binding to hemoglobin, shifting it to the R-state (Relaxed state) and releasing H⁺ and CO₂.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What factors cause a rightward shift in the oxygen dissociation curve?

A

A rightward shift is caused by:

Increased H⁺ (low pH).
Increased CO₂ concentration.
Increased temperature.
Increased 2,3-Bisphosphoglycerate (BPG).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does a rightward shift in the oxygen dissociation curve indicate?

A

A rightward shift indicates reduced hemoglobin affinity for oxygen, facilitating oxygen release to tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why is the Bohr Effect important in oxygen delivery?

A

The Bohr Effect ensures efficient oxygen release in metabolically active tissues where CO₂ and H⁺ are elevated, and oxygen is needed most.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does the Bohr Effect contribute to adaptation at high altitudes?

A

At high altitudes, increased 2,3-BPG production shifts the oxygen dissociation curve to the right, aiding oxygen release in low-oxygen conditions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What clinical conditions are related to the Bohr Effect?

A

Acidosis (low pH) or hypercapnia (high CO₂) can enhance oxygen unloading.
Alkalosis or hypocapnia can impair oxygen delivery to tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What happens to CO₂ at active tissues?

A

CO₂, a byproduct of cellular respiration, diffuses from tissues into systemic capillaries and enters red blood cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How is CO₂ converted in red blood cells at tissues?

A

CO₂ combines with water to form carbonic acid (H₂CO₃) via carbonic anhydrase, which dissociates into H⁺ and bicarbonate (HCO₃⁻).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the role of hemoglobin in pH regulation at tissues?

A

Hemoglobin binds H⁺ ions, stabilizing its T-state, reducing oxygen affinity, and facilitating oxygen release to tissues (Bohr Effect).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the chloride shift?

A

At tissues, HCO₃⁻ is transported out of red blood cells in exchange for Cl⁻ ions to maintain electrochemical balance.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens to CO₂ in the lungs?

A

CO₂ is released as H⁺ recombines with HCO₃⁻ to form carbonic acid, which is converted back into CO₂ and water by carbonic anhydrase. CO₂ is then exhaled.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What happens to hemoglobin in the lungs?

A

Oxygen binds to hemoglobin, displacing H⁺ ions and stabilizing the R-state (high oxygen affinity), allowing oxygen loading.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What enzyme is essential for CO₂ transport and pH regulation?

A

Carbonic anhydrase catalyzes the reversible conversion of CO₂ and water into carbonic acid (H₂CO₃).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the primary goal of systemic circulation (tissues)?

A

To offload oxygen and pick up CO₂ produced by metabolically active cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the primary goal of pulmonary circulation (lungs)?

A

To offload CO₂ and pick up oxygen from the alveoli for transport to tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How does CO₂ affect blood pH?

A

High CO₂ levels increase H⁺ concentration, lowering pH (acidic). Low CO₂ levels decrease H⁺ concentration, raising pH (alkaline).

32
Q

What are clinical conditions related to CO₂ and pH imbalance?

A

Respiratory acidosis: Caused by excess CO₂ (e.g., hypoventilation).
Respiratory alkalosis: Caused by reduced CO₂ (e.g., hyperventilation).

33
Q

What is 2,3-BPG, and where is it produced?

A

2,3-BPG (2,3-bisphosphoglycerate) is a metabolite produced in erythrocytes (red blood cells). It binds to hemoglobin and regulates oxygen affinity.

34
Q

What is the function of 2,3-BPG?

A

2,3-BPG binds to deoxygenated hemoglobin, stabilizing the T-state (tense state) and reducing hemoglobin’s oxygen affinity, promoting oxygen release to tissues.

35
Q

How does 2,3-BPG affect the oxygen dissociation curve?

A

2,3-BPG shifts the oxygen dissociation curve to the right, decreasing oxygen affinity and enhancing oxygen release to tissues.

36
Q

What happens to 2,3-BPG levels at high altitudes?

A

At high altitudes, 2,3-BPG levels increase (e.g., from 5 mmol/L to 8 mmol/L) to compensate for low oxygen availability by promoting oxygen release to tissues.

37
Q

What does the oxygen dissociation curve look like with no 2,3-BPG?

A

Without 2,3-BPG, the curve shifts to the left, indicating high oxygen affinity, which impairs oxygen release to tissues.

38
Q

How does increased 2,3-BPG help at high altitudes?

A

Increased 2,3-BPG reduces hemoglobin’s oxygen affinity, ensuring more oxygen is released to tissues, even at low partial pressures of oxygen.

39
Q

What is the normal level of 2,3-BPG in blood at sea level?

A

The normal concentration of 2,3-BPG in blood at sea level is 5 mmol/L.

40
Q

What are the physiological effects of 8 mmol/L 2,3-BPG at high altitude?

A

At 8 mmol/L, hemoglobin saturation decreases at high altitude, but an equivalent amount of oxygen is released to tissues as at sea level.

41
Q

What happens to 2,3-BPG levels in stored blood, and why is this important?

A

2,3-BPG levels decrease in stored blood, causing increased oxygen affinity, which can impair oxygen delivery during transfusions.

42
Q

How does 2,3-BPG relate to hypoxia or anemia?

A

In hypoxia or anemia, 2,3-BPG levels increase as a compensatory mechanism to enhance oxygen release to tissues.

43
Q

What is the clinical relevance of 2,3-BPG in high-altitude sickness?

A

Insufficient adaptation of 2,3-BPG levels at high altitudes can impair oxygen delivery to tissues, contributing to symptoms of altitude sickness.

44
Q

What happens to atmospheric pressure and oxygen levels at high altitudes?

A

At high altitudes, atmospheric pressure decreases, leading to lower partial pressure of oxygen (pO₂). However, the percentage of oxygen in the air remains the same (21%).

45
Q

Why does oxygen availability decrease at high altitudes?

A

The reduced atmospheric pressure at high altitudes lowers the partial pressure of oxygen (pO₂), reducing the driving force for oxygen diffusion into the bloodstream.

46
Q

What is the primary challenge for oxygen transport at high altitudes?

A

The reduced pO₂ decreases oxygen uptake in the lungs, potentially impairing oxygen delivery to tissues.

47
Q

How does 2,3-BPG help adapt to high altitudes?

A

Increased 2,3-BPG production shifts the oxygen dissociation curve to the right, reducing hemoglobin’s oxygen affinity and enhancing oxygen release to tissues.

48
Q

What are short-term physiological adaptations to high altitude?

A

Increased 2,3-BPG production.
Hyperventilation to increase oxygen uptake.

49
Q

What are long-term physiological adaptations to high altitude?

A

Increased red blood cell production (erythropoiesis).
Capillary growth (angiogenesis) to improve oxygen delivery.

50
Q

What happens if the body cannot adapt to high altitude?

A

Failure to adapt can result in altitude sickness, with symptoms like headache, fatigue, and shortness of breath. Severe cases may lead to HAPE or HACE.

51
Q

What is altitude sickness?

A

Altitude sickness occurs when the body fails to adapt to reduced oxygen availability at high altitudes, causing symptoms like headache, fatigue, and nausea.

52
Q

What treatments are used for altitude sickness?

A

Oxygen supplementation.
Medications like acetazolamide, which enhances ventilation and acclimatization.

53
Q

How does the body respond to reduced oxygen levels at high altitude?

A

Increased 2,3-BPG facilitates oxygen unloading to tissues.
Hyperventilation improves oxygen uptake.
Long-term, red blood cell production and capillary growth increase oxygen delivery.

54
Q

Why is training at high altitude beneficial for athletes?

A

High-altitude training stimulates red blood cell production and increases 2,3-BPG, improving oxygen delivery and enhancing performance in low-oxygen environments.

55
Q

Where does 2,3-BPG bind on hemoglobin?

A

2,3-BPG binds to the central cavity of hemoglobin, specifically in the T-state (deoxyhemoglobin).

56
Q

What is the effect of 2,3-BPG binding to hemoglobin?

A

2,3-BPG stabilizes the T-state of hemoglobin, reducing oxygen affinity and promoting oxygen release to tissues.

57
Q

How does 2,3-BPG affect the oxygen dissociation curve?

A

2,3-BPG shifts the oxygen dissociation curve to the right, facilitating oxygen unloading to tissues.

58
Q

Why does fetal hemoglobin (HbF) have a higher oxygen affinity than maternal hemoglobin (HbA)?

A

Fetal hemoglobin has gamma-globin chains instead of beta-globin chains, reducing its affinity for 2,3-BPG and increasing its oxygen affinity.

59
Q

Why is fetal hemoglobin’s lower affinity for 2,3-BPG important?

A

It allows fetal hemoglobin to extract oxygen from maternal blood, ensuring efficient oxygen transfer to the fetus.

60
Q

What is the role of 2,3-BPG in oxygen regulation?

A

2,3-BPG regulates hemoglobin’s oxygen affinity, ensuring oxygen is released to tissues as needed, especially during exercise, hypoxia, or at high altitudes.

61
Q

What happens to oxygen delivery when 2,3-BPG levels increase?

A

Increased 2,3-BPG levels reduce hemoglobin’s oxygen affinity, promoting more oxygen release to tissues.

62
Q

What is the difference between the T-state and R-state of hemoglobin?

A

T-state (tense): Low oxygen affinity, stabilized by 2,3-BPG.
R-state (relaxed): High oxygen affinity, favored when oxygen binds.

63
Q

Why is 2,3-BPG critical for maternal-fetal oxygen exchange?

A

Fetal hemoglobin’s reduced 2,3-BPG binding ensures it can extract oxygen from maternal hemoglobin for fetal oxygenation.

64
Q

What clinical conditions are related to 2,3-BPG levels?

A

Low 2,3-BPG: Impairs oxygen delivery to tissues (e.g., in stored blood).
High 2,3-BPG: Compensates during hypoxia or at high altitudes, enhancing oxygen release.

65
Q

What is allosteric regulation?

A

Allosteric regulation is a mechanism where molecules bind to specific sites on an enzyme or protein, altering its activity by changing its conformation.

66
Q

What is homotropic allosteric regulation?

A

Homotropic regulation occurs when the substrate itself acts as the allosteric modulator, affecting the binding of additional substrate molecules.

67
Q

What is the concerted model of homotropic regulation?

A

In the concerted model, the enzyme exists in equilibrium between two states:

T-state (Tense): Low substrate affinity.
R-state (Relaxed): High substrate affinity.
Substrate binding shifts all subunits simultaneously to the R-state.

68
Q

What is the sequential model of homotropic regulation?

A

In the sequential model, substrate binding induces a stepwise conformational change in individual subunits, increasing binding affinity gradually across the enzyme.

69
Q

What is heterotropic allosteric regulation?

A

Heterotropic regulation occurs when a molecule (effector) other than the substrate binds to the enzyme, influencing its activity positively or negatively.

70
Q

What is a positive heterotropic effector?

A

A positive effector enhances substrate binding or enzymatic activity by stabilizing the R-state of the enzyme.

71
Q

What is a negative heterotropic effector?

A

A negative effector decreases substrate binding or enzymatic activity by stabilizing the T-state of the enzyme.

72
Q

How does hemoglobin exhibit homotropic regulation?

A

Oxygen binding to one subunit of hemoglobin stabilizes the R-state, increasing oxygen affinity in the other subunits (cooperative binding).

73
Q

What are examples of heterotropic effectors for hemoglobin?

A

Positive: Oxygen.
Negative: CO₂, H⁺ (Bohr Effect), and 2,3-BPG, which stabilize the T-state and reduce oxygen affinity.

74
Q

Why is allosteric regulation important for enzymes in metabolism?

A

Allosteric regulation allows precise control of enzyme activity, enabling feedback inhibition and maintaining metabolic balance.

75
Q

How is allosteric regulation used in drug design?

A

Allosteric sites provide unique drug targets to modulate enzyme or protein function without competing with the substrate.

76
Q

What is the main difference between the concerted and sequential models?

A

Concerted Model: All subunits change conformation simultaneously.
Sequential Model: Subunits change conformation one at a time, gradually increasing substrate affinity.