Pentose Phosphate Pathway Overview

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Questions and Answers

What is one of the primary functions of the pentose phosphate pathway?

Conversion of pyruvate to lactate

Production of ATP

Synthesis of glycogen

Formation of NADPH (correct)

The pentose phosphate pathway occurs in the mitochondria of cells.

False

Name three tissues that have active pentose phosphate pathways.

Liver, adipose tissue, erythrocytes

Transketolase transfers __________ carbon groups from a ketose to an aldose.

2 Signup and view all the answers

Which enzyme requires TPP as a co-factor for its function?

Transketolase Signup and view all the answers

The non-oxidative phase of the pentose phosphate pathway is responsible for producing ribose precursors.

True Signup and view all the answers

What is the end product of the oxidative phase of the pentose phosphate pathway?

Ribulose-5-phosphate Signup and view all the answers

Match the following substances with their roles in the pentose phosphate pathway:

NADPH = Synthesis of fatty acids and steroids Ribose-5-phosphate = Nucleotide formation Glucose-6-phosphate = Starting substrate Glyceraldehyde-3-phosphate = Recycled product Signup and view all the answers

What is the primary function of glucose-6-phosphate dehydrogenase in the pentose phosphate pathway?

Generate NADPH Signup and view all the answers

Glucose-6-phosphate dehydrogenase is primarily regulated by __________ feedback inhibition by NADPH.

allosteric Signup and view all the answers

The accumulation of hydrogen peroxide in erythrocytes can extend their life span.

False Signup and view all the answers

What tripeptide is composed of g-glutamate, cysteine, and glycine?

Glutathione Signup and view all the answers

Match the following compounds with their roles:

NADPH = Reduces oxidized glutathione G6PD = Enzyme in pentose phosphate pathway H2O2 = Oxidative stress agent Primaquine = Drug causing oxidative stress in G6PD deficiency Signup and view all the answers

What condition can be induced by anti-malarial drugs in susceptible G6PD-deficient individuals?

Hemolytic anemia Signup and view all the answers

The gene for glucose-6-phosphate dehydrogenase is located on the Y chromosome.

False Signup and view all the answers

How many people worldwide are estimated to carry a mutated gene for glucose-6-phosphate dehydrogenase?

400 million Signup and view all the answers

Study Notes

Pentose Phosphate Pathway (PPP)

The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative route for glucose metabolism.
The PPP plays two significant roles:
- NADPH Production: It generates NADPH, essential for:
  - Fatty acid and steroid synthesis
  - Maintaining reduced glutathione for antioxidant activity, particularly in red blood cells (RBCs) to prevent hemolysis
- Ribose Synthesis: It synthesizes ribose, required for nucleic acid formation.
Three molecules of glucose-6-phosphate (G6P) are converted into:
- Three molecules of carbon dioxide (CO2)
- Three 5-carbon sugars rearranged to regenerate two molecules of G6P and one molecule of glyceraldehyde-3-phosphate.
G6P can be recycled back into the pathway, leading to further NADPH production.
Tissues with active PPP include:
- Liver
- Adipose tissue
- Adrenal cortex
- Testis
- Lactating mammary gland
- Erythrocytes

Reactions of the Pentose Phosphate Pathway

Occur in the cytosol.
Divided into two phases:
- Irreversible Oxidative Phase:
  - G6P undergoes dehydrogenation and decarboxylation, resulting in the production of a pentose, ribulose-5-phosphate.
- Reversible Nonoxidative Phase:
  - Ribulose-5-phosphate is converted back to G6P through a series of reactions involving key enzymes: transketolase and transaldolase.

Transketolase

Transfers 2-carbon groups from a ketose to an aldose.
This process converts the ketose (donor) into an aldose and the aldose (acceptor) into a ketose.
Requires thiamine pyrophosphate (TPP) as a cofactor for the transfer reaction.

Transaldolase

Transfers 3-carbon groups in a similar manner to transketolase.
Both transketolase and transaldolase catalyze reversible reactions.

The Oxidative Phase: Generating NADPH

This phase produces NADPH.

The Non-Oxidative Phase: Generating Ribose Precursors

This phase generates precursors for ribose synthesis.

Ribose Synthesis

Ribose can be synthesized in almost all tissues.
A fully functional PPP isn't necessary for ribose-5-phosphate synthesis in all tissues.
Many tissues (e.g., muscle) can synthesize ribose-5-phosphate by reversing the nonoxidative phase of the PPP using fructose-6-phosphate.

Regulation of the Pentose Phosphate Pathway

Glucose-6-Phosphate Dehydrogenase:
- The first step in the PPP and rate-limiting enzyme.
Allosteric Regulation:
- The pathway is feedback-inhibited by NADPH.
Inducible Enzyme:
- The pathway is induced by insulin.

Pentose Phosphate Pathway and Glutathione Peroxidase in Red Blood Cell Protection

Glutathione:
- Glutathione (GSH) is a tripeptide composed of γ-glutamate, cysteine, and glycine.
- The -SH groups of two glutathione molecules form a disulfide bond (GS-SG) when oxidized by various oxides and peroxides in cells.
- Glutathione reductase reduces GSSG back to two moles of GSH, requiring NADPH as a reducing agent.
Red Blood Cells (RBCs):
- The PPP is the only source of NADPH in RBCs, crucial for reducing oxidized glutathione.
- This reaction is critical because accumulation of hydrogen peroxide (H2O2) can shorten erythrocyte lifespan by causing oxidative damage to the cell membrane, leading to hemolysis.

Clinical Aspects: Impairment of the Pentose Phosphate Pathway

Erythrocyte Hemolysis:
- Deficiency in the PPP can lead to erythrocyte hemolysis.
- Genetic defects in glucose-6-phosphate dehydrogenase (G6PD), impairing NADPH generation, are common in Mediterranean and Afro-Caribbean populations.
- The G6PD gene is located on the X chromosome, making males more susceptible to the disorder.
- Over 400 million people carry a mutated G6PD gene (the most common genetic defect), but most are asymptomatic.

G6PD Deficiency

Hemolytic Anemia:
- Individuals with G6PD deficiency are at risk of developing hemolytic anemia when exposed to oxidative stress.
- Exposure to antimalarial drugs like primaquine can increase cellular production of superoxide and hydrogen peroxide, leading to a condition called primaquine sensitivity.
Other Oxidant Stress-Inducing Chemicals:
- Sulfonamides (antibiotics)
- Aspirin and NSAIDs
- Quinidine and quinine
- Fava beans (favism)

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Description

This quiz covers the Pentose Phosphate Pathway (PPP), highlighting its crucial roles in NADPH production and ribose synthesis. Understand the metabolic processes involved, including the conversion of glucose-6-phosphate and the tissues where the PPP is active. Test your knowledge on this essential metabolic pathway!