Pentose Phosphate Pathway Review

Flashcards covering the Pentose Phosphate Pathway, its phases, products, functions (NADPH uses), and clinical relevance (G6PD deficiency).

What is the subcellular localization of the pentose phosphate pathway (PPP)?

The PPP occurs in the cytoplasm of cells.

What are the primary products of the pentose phosphate pathway (PPP)?

The PPP produces NADPH and pentoses.

Which tissues have high utilization of the Pentose Phosphate Pathway?

The liver (especially in a fed state), mammary glands during lactation, adipose tissue (for fatty acid synthesis), and tissues involved in steroid hormone synthesis (testes, ovaries, placenta, adrenal cortex).

What is the role of the Pentose Phosphate Pathway in Red Blood Cells?

It serves as an antioxidant mechanism to maintain redox balance.

What are the two main phases of the Pentose Phosphate Pathway?

The irreversible, oxidative phase and the reversible, non-oxidative phase.

How many NADPH molecules are generated during the irreversible, oxidative phase of the PPP?

Two NADPH molecules are generated.

What is the initial substrate for the oxidative phase of the PPP?

Glucose-6 Phosphate (G6P).

What is the final product of the oxidative phase of the PPP, before entering the non-oxidative phase?

Ribulose-5 Phosphate.

Which enzyme converts Glucose-6 Phosphate into 6-Phosphogluconolactone in the PPP oxidative phase?

Glucose-6 Phosphate Dehydrogenase (G6PD).

How is Glucose-6 Phosphate Dehydrogenase (G6PD) activity regulated?

High concentrations of NADPH inhibit G6PD, while insulin upregulates its expression.

What are the key enzymes involved in the reversible, non-oxidative phase of the PPP?

Transketolase and Transaldolase.

What is the function of transketolase and transaldolase in the non-oxidative phase of the PPP?

They catalyze reactions that transfer carbons, interconverting sugars of varying lengths (3C to 7C).

What happens to Ribulose-5 phosphate if the cell needs to synthesize nucleotides?

It is converted into Ribose-5 phosphate, which is used for pyrimidine or purine synthesis.

What happens to intermediates of the PPP if there's a high demand for ATP or NADPH?

Ribulose-5-phosphate or other intermediates are converted into glycolytic intermediates (like glyceraldehyde-3-P and fructose-6-P) which re-enter glycolysis.

List some uses of NADPH by cells.

NADPH is used in redox balance (antioxidant mechanism via glutathione reductase), steroid hormone synthesis, detoxification by CYP450 enzymes, phagocytosis (respiratory burst), and nitric oxide synthesis.

How does NADPH protect cells from oxidative damage?

NADPH provides reducing equivalents for glutathione reductase, which regenerates reduced glutathione (G-SH). Reduced glutathione is then used by glutathione peroxidase to convert harmful hydrogen peroxide into water, thus neutralizing reactive oxygen species.

What role does NADPH play in Cytochrome P450 (CYP450) systems?

NADPH provides electrons to mitochondrial CYP450 enzymes for steroid hormone synthesis and to microsomal CYP450 enzymes for detoxification by introducing hydroxyl groups into compounds, increasing their polarity for excretion.

How is NADPH involved in phagocytosis in white blood cells?

During the respiratory burst, NADPH oxidase uses NADPH to reduce oxygen to superoxide anion, which is critical for killing engulfed microorganisms.

What is the consequence of Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency?

G6PD deficiency impairs the ability of erythrocytes to form NADPH, leading to increased oxidative stress and hemolytic anemia.

What are Heinz bodies and why do they form in G6PD deficiency?

Heinz bodies are aggregates of denatured or precipitated hemoglobin that attach to the red blood cell membrane. They form in G6PD deficiency due to oxidative stress, as the lack of NADPH prevents the detoxification of reactive oxygen species that damage hemoglobin.