Pentose Phosphate Pathway Quiz

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Questions and Answers

What is the primary role of G6PD in red blood cells?

To facilitate iron absorption in the bloodstream.

To regulate hemoglobin production.

To produce ATP for energy.

To detoxify free radicals using reduced glutathione. (correct)

Which factor is NOT a common trigger for hemolysis in individuals with G6PD deficiency?

Fava beans consumption.

Oxidant drugs like chloramphenicol.

Infections leading to inflammatory responses.

Uncontrolled diabetes. (correct)

What is the consequence of oxidative damage in RBCs due to G6PD deficiency?

Development of Heinz bodies. (correct)

Increase in hematocrit levels.

Enhanced oxygen transport capacity.

Formation of atherosclerotic plaques.

Which of the following is a key feature of nitrates and nitrites produced from nitric oxide?

They enhance vasodilation. Signup and view all the answers

How does G6PD deficiency provide evolutionary advantages against malaria?

It confers resistance to oxidative stress. Signup and view all the answers

Which nonoxidative function is primarily associated with NADPH?

Detoxification of drugs by cytochrome P450. Signup and view all the answers

What is a major consequence of the lack of alternative NADPH sources in RBCs?

Increased vulnerability to oxidative damage. Signup and view all the answers

Which process is primarily highlighted by the interaction of macrophages and reactive oxygen species (ROS)?

Destruction of pathogens. Signup and view all the answers

What is one of the primary functions of the cytochrome P450 monooxygenase system in the mitochondrial system?

Hydroxylation in steroid hormone biosynthesis Signup and view all the answers

Which mechanism is involved in the production of reactive oxygen species (ROS) during phagocytosis?

NADPH oxidase reducing O₂ to superoxide Signup and view all the answers

How does nitric oxide (NO) lead to vasodilation?

By activating guanylate cyclase and increasing cGMP Signup and view all the answers

What role do cytochrome P450 enzymes play in drug metabolism?

Hydroxylate drugs and increase their solubility Signup and view all the answers

Which type of nitric oxide synthase (NOS) is primarily involved in the immune defense mechanism?

iNOS Signup and view all the answers

What is a characteristic of the microsomal system of cytochrome P450 enzymes?

Detoxifies xenobiotics Signup and view all the answers

What is one outcome of NADPH oxidase deficiency?

Chronic granulomatous disease (CGD) Signup and view all the answers

Which of the following is NOT a function of cytochrome P450 enzymes?

Synthesis of nitric oxide Signup and view all the answers

Which enzyme is primarily responsible for the dehydrogenation of glucose 6-phosphate during the irreversible oxidative phase of the pentose phosphate pathway?

Glucose 6-phosphate dehydrogenase Signup and view all the answers

What are the primary products of the irreversible oxidative phase for each glucose 6-phosphate processed?

Ribulose 5-phosphate, CO₂, and 2 NADPH Signup and view all the answers

During the reversible nonoxidative phase of the pentose phosphate pathway, what are some of the sugar-phosphates that ribulose 5-phosphate can be converted into?

Ribose 5-phosphate and glycolytic intermediates Signup and view all the answers

What is one of the key roles of NADPH in the body?

Detoxification of hydrogen peroxide Signup and view all the answers

Why do red blood cells depend solely on the pentose phosphate pathway for NADPH production?

Due to their lack of mitochondria Signup and view all the answers

Which process describes how NADPH protects cells from oxidative stress?

By regenerating reduced glutathione Signup and view all the answers

What is the effect of insulin on glucose 6-phosphate dehydrogenase?

It upregulates the enzyme's activity Signup and view all the answers

What role does the Cytochrome P450 monooxygenase system play in metabolism?

Involved in the detoxification of drugs Signup and view all the answers

Study Notes

Pentose Phosphate Pathway (PPP)

Also known as the hexose monophosphate shunt
Occurs in the cytosol
Includes two phases: irreversible oxidative and reversible nonoxidative
Irreversible Oxidative Phase: Produces ribulose 5-phosphate, CO2, and 2 NADPH per glucose 6-phosphate
Reversible Nonoxidative Phase: Interconverts sugar-phosphates (e.g., ribose 5-phosphate, fructose 6-phosphate) to meet cellular energy or metabolic needs
No ATP is used or produced directly

Key Functions

NADPH Production: A major source of reducing power for
- Fatty acid and steroid biosynthesis
- Detoxification of reactive oxygen species (ROS)
Ribose 5-Phosphate Production: Required for nucleotide and nucleic acid synthesis
Five-Carbon Sugar Utilization: Metabolizes sugars from the diet or carbohydrate breakdown

Irreversible Oxidative Phase

Dehydrogenation of Glucose 6-Phosphate is the first step

Reversible Nonoxidative Phase

Converts ribulose 5-phosphate to either
- Ribose 5-phosphate for nucleotide synthesis
- Glycolytic intermediates (fructose 6-phosphate, glyceraldehyde 3-phosphate) to meet cellular energy or metabolic needs
Key enzymes: Transketolase (requires thiamine) and Transaldolase

Uses of NADPH

Reductive Biosynthesis: Supports synthesis of fatty acids and steroids
Detoxification of Hydrogen Peroxide: NADPH maintains reduced glutathione, critical for neutralizing ROS; RBCs depend solely on PPP for NADPH
Antioxidant Support: Protects cells from oxidative damage caused by ROS

Clinical Relevance

NADPH and antioxidant mechanisms play roles in minimizing oxidative stress linked to aging, inflammation, and diseases like cancer
Despite correlations between dietary antioxidants and reduced chronic disease risk, clinical trials have shown mixed results, emphasizing the complexity of dietary influences on health

Cytochrome P450 Monooxygenase System

Cytochrome P450 enzymes are a superfamily of heme-containing monooxygenases
Catalyze the hydroxylation of various substrates (e.g., steroids, drugs, toxins) using NADPH and molecular oxygen.
Reaction: R-H + O2 + NADPH + H+ → R-OH + H2O + NADP+
Functions in two locations:
- Mitochondrial System: Found in steroidogenic tissues (placenta, adrenal cortex, ovaries, testes) and liver. Hydroxylates intermediates in steroid hormone biosynthesis (from cholesterol)
Bile acid synthesis and vitamin D activation

Microsomal System

Located in the smooth endoplasmic reticulum, especially in the liver. Detoxifies xenobiotics (e.g., drugs, pesticides).
Hydroxylation increases solubility of toxins for excretion and allows conjugation with polar molecules (e.g., glucuronic acid).
Polymorphisms in cytochrome P450 genes (e.g., CYP3A4) influence drug metabolism.

Phagocytosis and Reactive Oxygen Species (ROS)

Phagocytosis : Neutrophils and macrophages engulf pathogens via receptor-mediated endocytosis, utilizing
- Oxygen-independent mechanisms: pH changes and lysosomal enzymes.
- Oxygen-dependent mechanisms: ROS generation via NADPH oxidase and myeloperoxidase (MPO)
Respiratory Burst : NADPH oxidase reduces O2 to superoxide (O2¯•),leading to ROS production (H2O2, HOCl, OH•); MPO converts H2O2 to hypochlorous acid (HOCl) a potent bactericidal agent
Clinical Note: NADPH oxidase deficiency causes chronic granulomatous disease (CGD), leading to persistent infections. MPO deficiency does not significantly increase infection susceptibility due to bactericidal activity of H2O2

Nitric Oxide (NO) Synthesis and Functions

Synthesis: Catalyzed by nitric oxide synthase (NOS), requiring arginine, O2, NADPH, and coenzymes (e.g., FMN, FAD, heme). Three types of NOS:
- eNOS (endothelium): Vasodilation
- nNOS (neural tissue): Neurotransmission
- iNOS (inducible in macrophages): Immune defense
Functions of NO:
- Vasodilation: Activates guanylate cyclase in vascular smooth muscle, increasing cGMP levels and promoting relaxation. Clinical applications: Nitroglycerin and sildenafil enhance NO-mediated vasodilation.
- Macrophage Defense: Combines with O2¯• to generate bactericidal radicals
- Platelet Inhibition: Prevents adhesion and aggregation via the cGMP pathway
- Neurotransmission: Acts as a signaling molecule in the nervous system

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Overview: Hereditary X-linked disorder characterized by hemolytic anemia due to the inability to detoxify oxidizing agents.
Clinical manifestations:
- Hemolytic anemia triggered by oxidative stress
- Neonatal jaundice due to increased unconjugated bilirubin
Evolutionary Note: G6PD deficiency provides resistance to Plasmodium falciparum malaria, similar to sickle cell trait and β-thalassemia minor.
Role of G6PD in Red Blood Cells (RBCs) G6PD is critical in the pentose phosphate pathway (PPP), producing NADPH needed to maintain reduced glutathione (G-SH); NADPH and G-SH protect RBCs from oxidative damage caused by free radicals and peroxides. Oxidative damage leads to Heinz bodies and rigid RBCs, removed by macrophages.

Precipitating Factors in Hemolysis

Common triggers include oxidant drugs (antibiotics, antimalarials, antipyretics), fava beans (favism), and infections.

Properties of Variant Enzymes

G6PD mutations result in enzymatic variants with altered properties (decreased activity, reduced stability, altered substrate or coenzyme affinity).
Severity correlates with residual enzymatic activity (Class I-III).

Molecular Biology of G6PD Deficiency

Over 400 variants of G6PD have been identified, most caused by missense mutations in the coding region (examples: G6PD A¯, G6PD Mediterranean)
Complete absence of G6PD activity is likely lethal.

Clinical Implications

Understanding G6PD variants and triggers can help manage patients with the deficiency, avoiding oxidative stressors and monitoring for complications like neonatal jaundice or chronic hemolysis.

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Description

Test your knowledge on the Pentose Phosphate Pathway (PPP), also known as the hexose monophosphate shunt. This quiz covers its two phases, key functions, and the biochemical significance of NADPH and ribose 5-phosphate production.