The Calvin–Benson Cycle and the Pentose Phosphate Pathway

A set of flashcards covering key concepts, terms, and functions from the lecture on the Calvin–Benson Cycle and the Pentose Phosphate Pathway.

What is the main function of the pentose phosphate pathway?

To generate NADPH for reductive biosynthesis and protect against oxidative stress.

Where does the pentose phosphate pathway occur in all organisms?

In the cytoplasm.

Which phase of the pentose phosphate pathway generates NADPH?

The oxidative phase.

What are the two main phases of the pentose phosphate pathway?

Oxidative phase and nonoxidative phase.

What is the first step of the oxidative phase of the pentose phosphate pathway?

The conversion of glucose 6-phosphate to ribulose 5-phosphate.

What enzyme initiates the oxidative phase of the pentose phosphate pathway?

Glucose 6-phosphate dehydrogenase.

What is the result of glucose 6-phosphate oxidation in the pentose phosphate pathway?

Produces ribulose 5-phosphate and generates NADPH.

What is glutathione's role in relation to redox balance?

Acts as a sulfhydryl buffer helping to maintain redox balance.

What compound is key in glutathione synthesis?

Cysteine.

Which enzyme hydrolyzes 6-phosphoglucono-δ-lactone in the pentose phosphate pathway?

Lactonase.

What is the primary function of glutathione peroxidase?

To detoxify peroxides.

What does glutathione reductase do?

Reduces GSSG back to GSH using NADPH.

What is the primary antioxidant role of glutathione?

To scavenge free radicals and peroxide compounds.

How does G6PD deficiency provide an evolutionary advantage?

Protects against malaria by compromising the growth of the parasite through oxidative stress.

What condition may occur in individuals with G6PD deficiency after consuming fava beans?

Hemolysis.

What is generated during the conversion of glucose 6-phosphate to ribulose 5-phosphate?

Two molecules of NADPH.

How is glutathione synthesized in cells?

From glutamate, cysteine, and glycine through sequential enzymatic reactions.

What does the ratio of reduced to oxidized glutathione typically remain at in cells?

500:1.

What happens to hemoglobin without adequate levels of glutathione?

It can cross-link and form aggregates known as Heinz bodies.

What role does acetaminophen play in relation to GSH?

It can deplete GSH levels leading to liver damage when overdosed.

What is the fate of the quinone metabolite of acetaminophen?

It can react with and be inactivated by glutathione.

What type of enzymes are glutathione-S-transferases (GSTs)?

Phase II enzymes that conjugate GSH to xenobiotics.

What do polymorphisms in GST isoforms affect?

The function and efficacy of detoxification processes.

What does the term 'xenobiotic' refer to?

A chemical compound that is foreign to a living organism.

How are drug sensitivities linked to genetics demonstrated in the Stateville Penitentiary malaria study?

Higher rates of hemolysis in G6PD deficient inmates exposed to primaquine.

What is the relationship between reactive oxygen species (ROS) and the function of GSH?

GSH detoxifies ROS to protect cells from oxidative damage.

Why is glucose 6-phosphate dehydrogenase important in maintaining GSH pools?

It generates NADPH, which is crucial for reducing oxidized glutathione.

What happens to individuals with G6PD deficiency when exposed to agents that generate peroxides?

They may experience hemolysis.

What metabolic process does glutathione participate in regarding pharmacogenetics?

Glutathione conjugation mediates drug detoxification.

What is the impact of dietary compounds on GSTs?

Some can induce enzyme activities while others may inhibit them.

What is the clinical significance of measuring γ-glutamyl transferase (GGT) levels?

It serves as an indicator of hepatobiliary disease.

How is derivative activity of GGT used in clinical tests?

To differentiate between liver and bone disease when alkaline phosphatase (ALP) levels are elevated.

What are the two forms of glutathione found in cells?

Reduced (GSH) and oxidized (GSSG) forms.

How does glutathione react with hydrogen peroxide?

It detoxifies it, preventing oxidative damage.

What major risk does primaquine pose to G6PD deficient individuals?

Acute hemolytic anemia.

What is the effect of NADPH on gluconate during the pentose phosphate pathway?

It helps convert gluconate to ribulose 5-phosphate.

What is the fate of excess NADPH produced?

Used in biosynthetic reactions and to maintain redox balance.

What role does GSH play in maintaining hemoglobin structure?

It keeps cysteine residues in a reduced form, preventing aggregation.

What is a major source of quinone metabolites of drugs?

Phase I metabolism by cytochrome P450 enzymes.

How does the pentose phosphate pathway relate to cellular and organism oxidative stress?

It provides a mechanism to generate NADPH, essential for detoxifying ROS.

Explain the significance of the G6PD allele map referenced in the lecture.

It illustrates the prevalence of G6PD deficiency and its evolutionary link to malaria resistance.

Describe the clinical significance of observing Heinz bodies in red blood cells.

They indicate oxidative damage and potential hemolytic anemia.

What are pyrimidine glycosides, and why are they significant?

Chemicals like Vicine that can induce hemolysis in G6PD-deficient individuals.

Which tissues predominantly utilize the pentose phosphate pathway?

Liver, adrenal gland, testes, adipose tissue, ovaries, mammary gland, and red blood cells.

What is 'favism'?

Hemolytic anemia triggered by eating fava beans in G6PD deficient individuals.

What are reactive metabolites formed from xenobiotic exposure?

Compound species that can form adducts with cellular components leading to toxicity.

What is the function of chaperone proteins in glutathione metabolism?

To assist in protein folding through the mediation of redox processes.

How can glutathione influence drug metabolism?

By forming non-toxic conjugates that facilitate excretion.

What is the clinical relevance of glutathione in drug toxicity?

It can alter the effects of drugs and their metabolites.

Which enzyme's activity is crucial in the detoxification of acetaminophen?

Glutathione-S-transferase.

Name a potential outcome of G6PD deficiency in P falciparum malaria cases.

Increased morbidity due to oxidative stress from the infection.

What are the key components in glutathione synthesis?

Glutamate, cysteine, and glycine.

What does elevated GGT activity indicate?

Possible liver dysfunction or biliary obstruction.

What are the common sources of increased plasma GGT activity?

Cholestasis, alcoholic liver disease, and hepatitis.

What role does cysteine play in the antioxidant function of glutathione?

It provides the thiol group necessary for its reducing action.

How does fava bean consumption affect G6PD-deficient individuals?

It induces oxidative stress leading to hemolysis.

What is the clinical significance of understanding G6PD deficiency?

It highlights the importance of considering genetic factors in pharmacotherapy.

In the context of the pentose phosphate pathway, what is the primary role of NADPH?

To serve as a reducing agent in biosynthetic reactions.

What can be a consequence of high levels of oxidized glutathione (GSSG)?

Reduced antioxidant capacity, leading to cellular damage.

Which drugs have been studied for their effects related to G6PD deficiency?

Primaquine and acetaminophen.

What type of imbalance can arise from glutathione depletion?

Oxidative stress.

Which organ has the highest activity of glutathione metabolism?

The liver.

What does the term 'hemolysis' refer to in the context of G6PD deficiency?

The destruction of red blood cells.

What is the importance of genetic testing in relation to G6PD deficiency?

It helps prevent adverse reactions to medications.

What are some dietary factors that can influence GSH levels?

Certain flavonoids may induce or inhibit GST activities.

What is the main protective role of glutathione in red blood cells?

Preserving hemoglobin's reduced state.

Name a characteristic symptom of fava bean hemolytic episodes in G6PD-deficient patients.

Dark red urine due to hemolysis.

What is the significance of the oxidative phase in the pentose phosphate pathway?

It is where NADPH and ribulose 5-phosphate are generated.

In terms of redox balance, how does glutathione contribute?

It acts as a reducing agent to combat oxidative stress.

What is the relationship between G6PD deficiency and malaria?

G6PD deficiency can confer resistance to malaria by harming parasite growth.

What happens to reduced glutathione levels during oxidative stress?

They are depleted as it is oxidized to GSSG.

What can be concluded about the evolutionary significance of G6PD variants?

They provide a survival advantage in malaria-endemic regions.

How does hemoglobin structure relate to glutathione levels?

Adequate glutathione maintains the correct thiol state of hemoglobin.

What is a common metabolite formed during the detoxification of various xenobiotics by GSH?

Mercapturic acid.

How does the pentose phosphate pathway contribute to overall cellular metabolism?

It provides NADPH and pentoses necessary for macromolecule synthesis.

Why are polymorphisms in G6PD significant in health care?

They can predispose individuals to adverse effects from certain medications.

What is the molecular structure of glutathione?

A tripeptide composed of glutamate, cysteine, and glycine.

How does chronic alcohol consumption affect glutathione levels?

It can lead to depletion of GSH and increased oxidative stress.

What chemical processes do GSH participate in regarding drug metabolism?

Glutathione-conjugation reactions that detoxify xenobiotics.

How do elevated GGT levels correlate with alcohol consumption?

High levels may indicate liver damage due to alcoholic liver disease.

What is the primary antioxidant action of glutathione in cells?

Scavenging of reactive oxygen species to prevent cellular damage.

In what condition does the pentose phosphate pathway play a critical role?

In providing reducing equivalents during times of oxidative stress.

How does the body regulate GSH levels?

Through synthesis and recycling by various enzymes and substrates.

What types of diseases could be indicated by abnormal GGT levels?

Liver diseases and biliary obstruction.”},{