Chapter 13

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Questions and Answers

What is the primary purpose of NADPH in the pentose phosphate pathway?

It is used to produce ATP.

It provides reducing equivalents for reductive biosynthesis and detoxification reactions. (correct)

It is used in the synthesis of ribulose 5-phosphate.

It acts as an energy source for glycolysis.

Which enzyme is responsible for the regulated step in the pentose phosphate pathway?

Fructose 1,6-bisphosphate aldolase

Ribulose bisphosphate carboxylase

Phosphofructokinase

Glucose 6-phosphate dehydrogenase (G6PD) (correct)

Which of the following statements is true regarding the oxidative portion of the pentose phosphate pathway?

It produces two NADPH molecules. (correct)

It consumes ATP as a cofactor.

It is reversible.

It produces ribose 5-phosphate directly.

How can the pentose phosphate pathway be entered aside from glucose 6-phosphate?

Through glycolytic intermediates like fructose 6-phosphate and glyceraldehyde 3-phosphate. Signup and view all the answers

What role does glutathione (GSH) play in the presence of NADPH?

It reduces hydrogen peroxide to water. Signup and view all the answers

What compound is produced by myeloperoxidase from peroxide and chloride ions?

Hypochlorous acid Signup and view all the answers

Which cellular process uses NADPH as a reducing equivalent?

Bile acid synthesis in the liver Signup and view all the answers

What is a consequence of the inhibition of glucose 6-phosphate dehydrogenase (G6PD)?

Decreased availability of ribose 5-phosphate. Signup and view all the answers

Which of the following is a key function of NADPH in red blood cells (RBCs)?

It aids in the reduction of superoxide radicals. Signup and view all the answers

Which of the following describes the non-oxidative reactions of the pentose phosphate pathway?

They interconvert sugars. Signup and view all the answers

What is the role of nitric oxide (NO) in the body?

Acts as a neurotransmitter and induces vasodilation Signup and view all the answers

What is the primary cause of hemolytic anemia in individuals with G6PD deficiency when treated with oxidant drugs?

Decreased reduced glutathione levels Signup and view all the answers

Which isozyme of nitric oxide synthase predominantly produces NO for defense against pathogens?

Inducible nitric oxide synthase (iNOS) Signup and view all the answers

What is the effect of grapefruit juice on atorvastatin levels?

Decreases the activity of CYP3A4 enzyme Signup and view all the answers

What is the underlying cause of septic shock related to nitric oxide production?

Excessive production of NO by inducible nitric oxide synthase (iNOS) Signup and view all the answers

Why do red blood cells (RBCs) suffer more from G6PD deficiency compared to liver cells?

Liver cells can utilize alternative pathways to generate NADPH Signup and view all the answers

In G6PD deficiency, which of the following statements is true regarding the synthesis of glutathione?

NADPH is crucial for converting oxidized glutathione to its reduced form Signup and view all the answers

Which of the following enzymes is most closely associated with the production of nitric oxide in the vasculature?

Endothelial nitric oxide synthase (eNOS) Signup and view all the answers

What substrate is used by nitric oxide synthase for the synthesis of NO?

Arginine Signup and view all the answers

Which metabolic pathway is primarily responsible for generating NADPH in cells?

Pentose phosphate pathway Signup and view all the answers

What is needed in large amounts for the regeneration of reduced glutathione in cells?

NADPH Signup and view all the answers

Which pathway do red blood cells rely on for generating NADPH?

Pentose phosphate pathway Signup and view all the answers

What is the primary issue in red blood cells that affects their ability to regenerate glutathione?

Decreased production of NADPH Signup and view all the answers

Which enzyme's activity can be used to assess thiamine status in red blood cells?

Transketolase Signup and view all the answers

Which of the following statements about red blood cells is true?

They lack glucose 6-phosphatase. Signup and view all the answers

What essential prosthetic group is derived from vitamin thiamine?

Thiamine pyrophosphate (TPP) Signup and view all the answers

Why do red blood cells not generate ATP through the pentose phosphate pathway?

The pathway does not generate ATP. Signup and view all the answers

What is the role of NADPH in red blood cells?

Regenerate reduced glutathione. Signup and view all the answers

Which enzyme is absent in red blood cells, thus limiting their use in certain metabolic processes?

Glucose 6-phosphatase Signup and view all the answers

What metabolic feature uniquely defines red blood cells compared to other cells?

Dependence on the pentose phosphate pathway for NADPH production. Signup and view all the answers

Study Notes

Pentose Phosphate Pathway (PPP)

The pathway consists of two irreversible oxidative reactions followed by reversible sugar-phosphate interconversions.
No ATP is produced or consumed during the cycle.
The oxidative part generates NADPH, crucial for reductive biosynthesis and detoxification.

Key Reactions

Glucose 6-phosphate is irreversibly converted to ribulose 5-phosphate, yielding two NADPH.
The enzyme glucose 6-phosphate dehydrogenase (G6PD) regulates this step and is inhibited by NADPH.
Reversible reactions provide ribose 5-phosphate necessary for nucleotide and nucleic acid synthesis.

NADPH Functions

Serves as a reducing agent for fatty acid synthesis, steroid hormone production, and the detoxification of xenobiotics.
Essential for red blood cells to reduce hydrogen peroxide, ensuring the proper function of glutathione (GSH).
GSH reduces peroxide to water, with oxidized glutathione (GSSH) being converted back to GSH using NADPH.

Mitochondrial P450 Monooxygenase System

NADPH supplies reducing equivalents for steroid hormone synthesis, bile acid production, and vitamin D activation.

Immune Response

NADPH aids phagocytes in eliminating pathogens, producing superoxide radicals via NADPH oxidase.
Myeloperoxidase generates hypochlorous acid from peroxide, enhancing bactericidal activity.

Genetic Defects and Hemolytic Anemia

G6PD deficiency leads to impaired NADPH production, critically affecting red blood cells lacking alternative NADPH sources.
Manifestations include hemolytic anemia triggered by oxidant drugs or fava beans; severity depends on residual enzyme activity.
Class I variants of G6PD deficiency are linked to chronic nonspherocytic hemolytic anemia and neonatal jaundice.

Septic Shock

Characterized by low blood pressure and inadequate organ perfusion due to severe inflammatory response.
The situation involves increased nitric oxide (NO) levels; overproduction by inducible nitric oxide synthase (iNOS) leads to vasodilation and hypotension.

Atorvastatin and Grapefruit Juice Interaction

Atorvastatin, a CYP3A4 substrate, has its effects heightened by grapefruit juice which inhibits this enzyme, increasing potential side effects.
P450 enzymes primarily function to hydroxylate hydrophobic molecules, enhancing solubility for excretion.

X-Linked G6PD Deficiency Impacts

Hemizygous males show more RBC pathophysiology due to their exclusive reliance on PPP for NADPH regeneration.
Liver cells have alternative pathways for NADPH production, explaining their relative protection against damage.

Thiamine Status Assessment

Transketolase in red blood cells acts as a marker for thiamine status since RBCs lack mitochondria and mitochondrial enzymes reliant on thiamine pyrophosphate (TPP).

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Description

This quiz explores the pentose phosphate pathway, which includes key oxidative reactions and subsequent reversible sugar-phosphate interconversions. Understand the role of NADPH in reductive biosynthesis and detoxification processes. Test your knowledge of this essential metabolic pathway.