Biochem - Metabolism (Respiratory burst & related disorders)

Question 1

What is another name for respiratory burst? What does it involve?

Answer 1

Respiratory burst (oxidative burst); Involves the activation of the phagocyte NADPH oxidase complex (e.g., in neutrophils, monocytes), which utilizes O2 as a substrate.

Question 2

What are 2 cells in which respiratory burst occurs?

Answer 2

Neutrophils, monocytes

Question 3

What is the important role of respiratory burst?

Answer 3

Plays an important role in the immune response => rapid release of reactive oxygen species (ROS).

Question 4

What role does NADPH play with regard to ROS?

Answer 4

Note that NADPH plays a role in both the creation and neutralization of ROS

Question 5

What is myeloperoxidase, and what is its role in sputum?

Answer 5

Myeloperoxidase is a blue-green heme-containing pigment that gives sputum its color

Question 6

How do CGD patients compensate for their deficiency?

Answer 6

Phagocytes of patients with CGD can utilize H2O2 generated by invading organisms and convert it to ROS.

Question 7

For what kind of infections are CGD patients at increased risk, and why?

Answer 7

Patients are at increased risk for infection by catalase (+) species (e.g., S. aureus, Aspergillus) capable of neutralizing their own H2O2, leaving phagocytes without ROS for fighting infections.

Question 8

What is the source of pyocyanin, and what role does it play related to respiratory burst?

Answer 8

Pyocyanin of P. aeruginosa functions to generate ROS to kill competing microbes.

Question 9

What/Where is lactoferrin, and what role does it play?

Answer 9

Lactoferrin is a protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation.

Question 10

What is the deficiency in granulomatous disease?

Answer 10

NADPH oxidase (deficiency = chronic granulomatous disease)

Question 11

What 2 enzymes relevant to respiratory burst (oxidative burst) require selenium?

Answer 11

(1) Glutathione peroxidase (requires selenium) (2) Glutathione reductase (requires selenium)

Question 12

What are the forms of glutathione in respiratory burst?

Answer 12

Glutathione (reduce/oxidized)

Question 13

What is another name for bleach (HOCl radical)?

Answer 13

Bleach (hypochlorite)

Question 14

What are the 6 major enzymes/steps of respiratory burst (oxidative burst)? Draw them out.

Answer 14

(1) NADPH oxidase (2) Superoxide dismutase (3) Myeloperoxidase (4) Glutathione peroxidase (requires selenium) (5) Glutathione reductase (requires selenium) (6) G6PD; See p. 105 in First Aid 2014 in the visual at the bottom of the page

Question 15

What is the role of glutathione? What is necessary to keep it reduced?

Answer 15

NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides.

Question 16

What is the result of low NADPH? Give 4 examples of factors/drugs causing this.

Answer 16

Low NADPH in RBCs lead to hemolytic anemia due to poor RBC defense against oxidizing agents (e.g., fava beans, sulfonamides, primaquine, antituberculosis drugs).

Question 17

Explain why infection can precipitate hemolysis.

Answer 17

Infection can also precipitate hemolysis (free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage).

Question 18

What is the mode of inheritance of G6PD deficiency?

Answer 18

X-linked recessive disorder

Question 19

What is the most common human enzyme deficiency?

Answer 19

Glucose-6-phosphate dehydrogenase deficiency

Question 20

In what patient population is G6PD more prevalent?

Answer 20

More prevalent among blacks

Question 21

What advantage does G6PD deficiency confer?

Answer 21

Increased malarial resistance

Question 22

What are 2 hematological abnormalities seen on blood smear of G6PD deficiency patients? Briefly explain what causes each.

Answer 22

(1) Heinz bodies - oxidized Hemoglobin precipitated within RBCs (2) Bite cells - result from the phagocytic removal of Heinz bodies by splenic macrophages; Think: “BITE into some HEINZ ketchup”

Question 23

Draw a diagram depicting the actions of the following enzymes and their relation: (1) Glucose-6-Phosphate dehydrogenase (2) Glutathione reductase (3) Glutathione peroxidase.

Answer 23

See p. 106 in First Aid 2014 for visual at top of the page