The Pentose Phosphate Pathway

What is the primary purpose of the Pentose Phosphate Pathway (PPP)>

It provides NADPH and Ribose-5-phosphate (R5P).

What two main products does PPP generate?

• NADPH (for reductive biosynthesis and antioxidant defense)

• Ribose-5-phosphate (for nucleotide biosynthesis).

• No ATP is produced.

Why doesn’t the Pentose Phosphate Pathway generate ATP?

Its purpose is to generate NADPH and R5P, not energy, because these molecules are essential for biosynthesis and antioxidant defense, rather than energy metabolism.

In which tissues and cellular locations does the PPP operate?

Location: Cytosol. Active in tissues synthesizing fatty acids/steroids (e.g., liver, mammary glands, adrenal glands, adipose tissue) because they require NADPH for biosynthesis.

Why is PPP more active in certain tissues?

Active in RBCs to maintain reduced iron and protect against oxidative stress.

What are the two phases of the PPP, and what does each produce?

Oxidative phase (irreversible): Produces NADPH by oxidizing glucose-6-phosphate. Non-oxidative phase (reversible): Produces ribose-5-phosphate (R5P) and interconverts sugar phosphates.

How is NADPH used in the body? List three roles.

Biosynthesis: Fatty acids, cholesterol, steroid hormones. Antioxidant defense: Maintains reduced glutathione to neutralize ROS. Immune defense: Helps generate ROS in neutrophils (respiratory burst).

Why is ribose-5-phosphate critical for the cell? What types of cells have high PPP activity because of this?

Importance: R5P is a precursor for nucleotide synthesis (RNA/DNA). High PPP activity: Rapidly dividing cells (e.g., tumor cells) due to their need for constant DNA replication.

What are the roles of transketolase and transaldolase in the non-oxidative phase of PPP?

Transketolase: Transfers two-carbon fragments between sugar phosphates. Transaldolase: Transfers three-carbon fragments between sugar phosphates. Both enzymes interconvert sugar molecules.

What is the role of NADPH in cholesterol synthesis? Which enzyme requires NADPH?

Role: NADPH reduces substrates during biosynthesis. Enzyme: HMG-CoA reductase (rate-limiting step in cholesterol synthesis).

How does the cytochrome P450 system utilize NADPH?

Cytochrome P450 monooxygenase catalyzes the hydroxylation of substrates using NADPH. Process: Transfers one oxygen atom to the substrate (forms OH group) and one to hydrogen (forms H2O).

How does NADPH protect erythrocytes from oxidative damage?

Maintains reduced glutathione (via glutathione reductase), which detoxifies hydrogen peroxide (H2O2) into water. Prevents the formation of methemoglobin (Fe3+), ensuring proper oxygen transport by hemoglobin.

What is G6PD deficiency, and how does it relate to the PPP?

X-linked recessive disorder causing reduced NADPH production in RBCs. Result: RBCs are prone to oxidative damage, leading to hemolytic anemia, especially after exposure to oxidative stressors (e.g., fava beans, sulfa drugs, infections).

How does chronic granulomatous disease (CGD) impair the immune system, and what role does NADPH play in this condition?

Cause: NADPH oxidase deficiency, leading to impaired ROS production in neutrophils. Result: Decreased respiratory burst, increasing susceptibility to catalase-positive organisms.

What enzyme regenerates reduced glutathione from its oxidized form, and what cofactor is required?

Enzyme: Glutathione reductase. Cofactor: NADPH.

Describe how NADPH is involved in the respiratory burst in neutrophils.

NADPH fuels the generation of superoxide and hydrogen peroxide, which are used to destroy microbes during the respiratory burst.