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Questions and Answers
What is the primary aim of the pentose phosphate pathway?
What is the primary aim of the pentose phosphate pathway?
Which of the following tissues primarily relies on NADPH for fatty acid biosynthesis?
Which of the following tissues primarily relies on NADPH for fatty acid biosynthesis?
What is formed during the irreversible oxidative reactions of the pentose phosphate pathway?
What is formed during the irreversible oxidative reactions of the pentose phosphate pathway?
Where does the pentose phosphate pathway primarily occur within the cell?
Where does the pentose phosphate pathway primarily occur within the cell?
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Which component is critical for detoxifying hydrogen peroxide in erythrocytes?
Which component is critical for detoxifying hydrogen peroxide in erythrocytes?
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What are the products of the irreversible reaction involving 6-phosphogluconolactone hydrolase?
What are the products of the irreversible reaction involving 6-phosphogluconolactone hydrolase?
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Which coenzyme is required for the activity of transketolase?
Which coenzyme is required for the activity of transketolase?
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What distinguishes ribulose from ribose?
What distinguishes ribulose from ribose?
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What defines ribulose and xylulose as epimers?
What defines ribulose and xylulose as epimers?
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Which B vitamins are particularly emphasized in their role in metabolism, specifically carbohydrate metabolism?
Which B vitamins are particularly emphasized in their role in metabolism, specifically carbohydrate metabolism?
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What is the primary role of transketolase in carbohydrate metabolism?
What is the primary role of transketolase in carbohydrate metabolism?
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Which of the following compounds is formed by the action of transaldolase?
Which of the following compounds is formed by the action of transaldolase?
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Which of the following statements correctly describes NADPH's function?
Which of the following statements correctly describes NADPH's function?
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What are the products formed when transketolase transfers a 2 carbon unit from Xylulose 5 P to Ribose 5 P?
What are the products formed when transketolase transfers a 2 carbon unit from Xylulose 5 P to Ribose 5 P?
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What is the primary product produced by the oxidative portion of the pentose phosphate pathway?
What is the primary product produced by the oxidative portion of the pentose phosphate pathway?
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Which reactions result in the removal of 3 CO2 molecules in carbohydrate metabolism?
Which reactions result in the removal of 3 CO2 molecules in carbohydrate metabolism?
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Under which conditions is ribose 5-phosphate biosynthesis favored over NADPH production?
Under which conditions is ribose 5-phosphate biosynthesis favored over NADPH production?
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Which enzyme catalyzes the irreversible oxidation of glucose 6-phosphate to produce NADPH?
Which enzyme catalyzes the irreversible oxidation of glucose 6-phosphate to produce NADPH?
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Which of the following reactions is categorized as a non-oxidative reaction in the pentose phosphate pathway?
Which of the following reactions is categorized as a non-oxidative reaction in the pentose phosphate pathway?
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What role does NADPH play in the pentose phosphate pathway?
What role does NADPH play in the pentose phosphate pathway?
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Study Notes
HMP Shunt Overview
- The HMP shunt is an alternative pathway for glucose oxidation.
- Its goal is not ATP or energy production.
- It produces NADPH, acting as a biochemical reducing agent (hydrogen carrier). NADPH plays no role in energy production, as NADH and FADH2 are used in the electron transport chain (ETC).
- It synthesizes ribose 5-phosphate, needed for nucleotide synthesis.
Pentose Phosphate Pathway (PPP)
- The aim of the PPP is to form pentose sugar.
- Also known as the hexose monophosphate shunt (HMP) shunt.
- Begins with glucose 6-phosphate (G6P) converting it into ribose.
- The first phase produces 6-phosphogluconate.
HMP Shunt Steps (Oxidative)
- Three reactions lead to the formation of ribulose 5-phosphate, CO2, and two NADPH molecules per glucose 6-phosphate oxidized.
- This part of the pathway is crucial in the liver, lactating mammary glands, adipose tissue, erythrocytes, testes, ovaries, placenta, and adrenal cortex. It is also vital in phagocytic cells.
HMP Shunt Steps (Non-Oxidative)
- These reversible reactions convert sugars with 3 to 7 carbon atoms.
- Ribulose 5-phosphate can be converted into ribose 5-phosphate (needed for nucleotide synthesis).
- Or into intermediates of glycolysis (fructose 6-phosphate and glyceraldehyde 3-phosphate).
HMP Shunt Regulation
- Cells involved in reductive biosynthesis (e.g., fatty acid, amino acid, steroid synthesis) need more NADPH than ribose 5-phosphate.
- Oxidative reactions produce ribulose 5-phosphate, which can be converted into ribose 5-phosphate through non-oxidative reactions.
- When the need for ribose exceeds NADPH, the non-oxidative reactions produce ribose from glycolytic intermediates.
NADPH Uses
- Serves in reductive biosynthesis (synthesis of fatty acids, amino acids, and steroids).
Reactive Oxygen Species (ROS)
- Formed from the partial reduction of molecular oxygen.
- ROS (like superoxide, hydrogen peroxide, hydroxyl radical) are continuously produced.
- This occurs as by-products of aerobic metabolism, toxic environmental substances, and reduced antioxidant levels.
- ROS damages DNA, proteins, and lipids, leading to cellular damage and disease.
NADPH and ROS Reduction
- NADPH provides reducing equivalents for processes like glutathione reductase to reduce hydrogen peroxide.
- It is needed and produced by the pentose phosphate pathway for effective detoxification of reactive oxygen species (ROS).
Phagocytosis and Respiratory Burst
- NADPH oxidase reduces oxygen in phagocytic cells to make superoxide (O2-), a toxic free radical that kills bacteria.
- Superoxide is converted to more reactive ROS (like hydrogen peroxide).
- H2O2, in presence of chloride ions and myeloperoxidase (MPO), kills bacteria by forming hypochlorous acid.
- Peroxide can reduce to the hydroxyl radical and then reduced to water with catalase and glutathione peroxidase.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- G6PD catalyzes the initial, irreversible oxidation of glucose 6-phosphate.
- The deficiency impairs NADPH production in erythrocytes, leading to hemolysis (destruction of red blood cells).
- Oxidative stress, certain drugs (e.g., antimalarials, antibiotics), fava beans, and infections are precipitating factors in G6PD deficiency.
G6PD Deficiency: Effects
- Diminished NADPH production leads to impaired regeneration of the reduced glutathione pool.
- Reduced detoxification of free radicals and peroxides leads to damage within cells.
- Increased membrane fragility especially in RBC leading to hemolysis (RBC rupture).
G6PD Deficiency: Precipitating factors
- Oxidant drugs: Antibiotics, Antimalarials, Antipyretics
- Favism: Related to Mediterranean diet containing fava beans
- Infections: Trigger the generation of free radicals within macrophages which diffuse to RBC and cause oxidative damage
G6PD Deficiency: Important roles of the enzyme
- The only means of NADPH production in the erythrocytes.
- The erythrocyte lacks nucleus and ribosomes so cannot renew the enzyme supply.
- Erythrocytes carry oxygen in hemoglobin and thus, are more susceptible to ROS.
- Muscle cannot replenish ribose 5P if the first two phases of HMP are deficient; ribose 5P is provided by the reverse of HMP phase 2 from glycolytic products.
PPP and Ribose-5-Phosphate
- Ribose-5-phosphate is needed for nucleic acid biosynthesis.
- Ribose is a critical component for nucleotides, further leading to DNA and RNA synthesis.
- The HMP shunt is very important for providing ribose 5-phosphate in cells that produce a high rate of nucleotides and nucleic acids.
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Description
Explore the intricacies of the HMP shunt and the Pentose Phosphate Pathway (PPP) through this quiz. Understand the role of NADPH and the synthesis of ribose 5-phosphate in cellular metabolism. Test your knowledge on the steps and functions of this critical metabolic pathway.
