Biochem - Metabolism (Respiratory burst & related disorders) Flashcards
Pg. 105-106 in First Aid 2014 Sections include: -Respiratory burst (oxidative burst) -Glucose-6-phosphate dehydrogenase deficiency
What is another name for respiratory burst? What does it involve?
Respiratory burst (oxidative burst); Involves the activation of the phagocyte NADPH oxidase complex (e.g., in neutrophils, monocytes), which utilizes O2 as a substrate.
What are 2 cells in which respiratory burst occurs?
Neutrophils, monocytes
What is the important role of respiratory burst?
Plays an important role in the immune response => rapid release of reactive oxygen species (ROS).
What role does NADPH play with regard to ROS?
Note that NADPH plays a role in both the creation and neutralization of ROS
What is myeloperoxidase, and what is its role in sputum?
Myeloperoxidase is a blue-green heme-containing pigment that gives sputum its color
How do CGD patients compensate for their deficiency?
Phagocytes of patients with CGD can utilize H2O2 generated by invading organisms and convert it to ROS.
For what kind of infections are CGD patients at increased risk, and why?
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.
What is the source of pyocyanin, and what role does it play related to respiratory burst?
Pyocyanin of P. aeruginosa functions to generate ROS to kill competing microbes.
What/Where is lactoferrin, and what role does it play?
Lactoferrin is a protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation.
What is the deficiency in granulomatous disease?
NADPH oxidase (deficiency = chronic granulomatous disease)
What 2 enzymes relevant to respiratory burst (oxidative burst) require selenium?
(1) Glutathione peroxidase (requires selenium) (2) Glutathione reductase (requires selenium)
What are the forms of glutathione in respiratory burst?
Glutathione (reduce/oxidized)
What is another name for bleach (HOCl radical)?
Bleach (hypochlorite)
What are the 6 major enzymes/steps of respiratory burst (oxidative burst)? Draw them out.
(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
What is the role of glutathione? What is necessary to keep it reduced?
NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides.
What is the result of low NADPH? Give 4 examples of factors/drugs causing this.
Low NADPH in RBCs lead to hemolytic anemia due to poor RBC defense against oxidizing agents (e.g., fava beans, sulfonamides, primaquine, antituberculosis drugs).
Explain why infection can precipitate hemolysis.
Infection can also precipitate hemolysis (free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage).
What is the mode of inheritance of G6PD deficiency?
X-linked recessive disorder
What is the most common human enzyme deficiency?
Glucose-6-phosphate dehydrogenase deficiency
In what patient population is G6PD more prevalent?
More prevalent among blacks
What advantage does G6PD deficiency confer?
Increased malarial resistance
What are 2 hematological abnormalities seen on blood smear of G6PD deficiency patients? Briefly explain what causes each.
(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”
Draw a diagram depicting the actions of the following enzymes and their relation: (1) Glucose-6-Phosphate dehydrogenase (2) Glutathione reductase (3) Glutathione peroxidase.
See p. 106 in First Aid 2014 for visual at top of the page
