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Questions and Answers
What is the primary role of reduced glutathione (GSH) in red blood cells?
What is the primary role of reduced glutathione (GSH) in red blood cells?
Which factor inhibits the activity of glucose-6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway?
Which factor inhibits the activity of glucose-6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway?
What is the consequence of GSH deficiency in red blood cells?
What is the consequence of GSH deficiency in red blood cells?
What initiates the synthesis of ribose-5-phosphate in glucose-6-phosphate dehydrogenase-deficient individuals?
What initiates the synthesis of ribose-5-phosphate in glucose-6-phosphate dehydrogenase-deficient individuals?
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In which type of cells is the oxidative phase of the pentose phosphate pathway particularly active?
In which type of cells is the oxidative phase of the pentose phosphate pathway particularly active?
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What role does amylo-α(l,6)-glucosidase play in glycogen metabolism?
What role does amylo-α(l,6)-glucosidase play in glycogen metabolism?
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Which condition is primarily associated with the deficiency of debranching enzyme?
Which condition is primarily associated with the deficiency of debranching enzyme?
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How does glucagon influence glycogen metabolism?
How does glucagon influence glycogen metabolism?
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What effect does insulin have on glycogen metabolism?
What effect does insulin have on glycogen metabolism?
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What triggers the release of epinephrine and its consequent effects on glycogen metabolism?
What triggers the release of epinephrine and its consequent effects on glycogen metabolism?
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What is the active form of glycogen synthase known as?
What is the active form of glycogen synthase known as?
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How is glycogen phosphorylase activated from its inactive form?
How is glycogen phosphorylase activated from its inactive form?
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What is the primary product of the reaction catalyzed by debranching enzyme after removing the last glucose from a branch point?
What is the primary product of the reaction catalyzed by debranching enzyme after removing the last glucose from a branch point?
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What is the primary function of the oxidative phase of the pentose phosphate pathway?
What is the primary function of the oxidative phase of the pentose phosphate pathway?
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Which enzyme catalyzes the rate-limiting step of the oxidative phase?
Which enzyme catalyzes the rate-limiting step of the oxidative phase?
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What are the key products of the oxidative phase of the pentose phosphate pathway?
What are the key products of the oxidative phase of the pentose phosphate pathway?
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The nonoxidative phase of the pentose phosphate pathway involves the conversion of which molecule to ribose-5-phosphate?
The nonoxidative phase of the pentose phosphate pathway involves the conversion of which molecule to ribose-5-phosphate?
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What type of reaction does transketolase facilitate in the nonoxidative phase?
What type of reaction does transketolase facilitate in the nonoxidative phase?
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Phosphorylation of which proteins is critical for glycogen synthesis?
Phosphorylation of which proteins is critical for glycogen synthesis?
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What is the main role of NADPH produced in the pentose phosphate pathway?
What is the main role of NADPH produced in the pentose phosphate pathway?
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Which of the following is NOT a product of the oxidative phase in the pentose phosphate pathway?
Which of the following is NOT a product of the oxidative phase in the pentose phosphate pathway?
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In which cellular processes is the pentose phosphate pathway most active?
In which cellular processes is the pentose phosphate pathway most active?
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Which coenzyme is significantly supplied by the pentose phosphate pathway?
Which coenzyme is significantly supplied by the pentose phosphate pathway?
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What is the outcome when pentose sugars are not needed for biosynthetic reactions?
What is the outcome when pentose sugars are not needed for biosynthetic reactions?
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Which enzyme's activity in the eye requires NADPH?
Which enzyme's activity in the eye requires NADPH?
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What is another name for the pentose phosphate pathway?
What is another name for the pentose phosphate pathway?
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Which metabolic process does erythrose-4-phosphate participate in?
Which metabolic process does erythrose-4-phosphate participate in?
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Why is the oxidative phase of the pentose phosphate pathway particularly active in red blood cells?
Why is the oxidative phase of the pentose phosphate pathway particularly active in red blood cells?
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Which hormone primarily promotes glycogenesis following a meal?
Which hormone primarily promotes glycogenesis following a meal?
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What is the function of phosphoglucomutase in glycogen metabolism?
What is the function of phosphoglucomutase in glycogen metabolism?
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What is required for the synthesis of UDP-glucose?
What is required for the synthesis of UDP-glucose?
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Which enzyme catalyzes the transfer of the glucosyl group of UDP-glucose to glycogen?
Which enzyme catalyzes the transfer of the glucosyl group of UDP-glucose to glycogen?
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What is the role of amylo-α(l,4 to 1,6)-glucosyl transferase in glycogen synthesis?
What is the role of amylo-α(l,4 to 1,6)-glucosyl transferase in glycogen synthesis?
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During glycogenolysis, what is the first step in breaking down glycogen?
During glycogenolysis, what is the first step in breaking down glycogen?
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How does glycogen phosphorylase stop its action during glycogenolysis?
How does glycogen phosphorylase stop its action during glycogenolysis?
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Which molecule acts as a primer protein to initiate glycogen synthesis?
Which molecule acts as a primer protein to initiate glycogen synthesis?
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Study Notes
Carbohydrate Metabolism Lecture 3: Glycogen & Hexose Monophosphate Shunt
- Glycogen metabolism involves the synthesis and degradation. These processes are carefully regulated to maintain sufficient glucose for energy needs. Insulin, glucagon, and epinephrine are the primary hormones that control these processes.
- Glycogenesis (glycogen synthesis) occurs in the liver after a meal when blood glucose levels are high.
- Glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase. This enzyme contains a phosphoryl group attached to a reactive serine residue.
- UDP-glucose formation is followed by glycogen synthesis from UDP-glucose, catalyzed by two enzymes.
- Glycogen synthase catalyzes the transfer of the glucosyl group of UDP-glucose to the non-reducing ends of glycogen.
- Amylo-α(1,4 to 1,6)-glucosyl transferase (Branching enzyme) creates the α(1,6) linkages for branches.
- Glycogen synthesis is believed to be instigated by the transfer of glucose from UDP-glucose to a specific tyrosine residue called glycogenin on a "primer" protein.
- Glycogenolysis (glycogen degradation) involves two key reactions.
- Removal of glucose from non-reducing ends: Glycogen phosphorylase breaks down α(1,4) linkages releasing glucose-1-phosphate. Glycogen phosphorylase stops when it reaches four glucose residues from a branch point.
- Hydrolysis of α(1,6) glycosidic bonds at branch points: Amylo-α(1,6)-glucosidase (also called Debranching enzyme) transfers outer three of four glucose units to a nearby non-reducing end, and then removes the single glucose residue at each branch point. The product is free glucose.
- Cori's disease is a glycogen storage disease. It's caused by a deficiency in the debranching enzyme. Patients exhibit enlarged livers (hepatomegaly) and low blood sugar (early fasting hypoglycemia).
Regulation of Glycogen Metabolism
- Glycogen synthesis and degradation are regulated through a complex mechanism involving insulin, glucagon, and epinephrine.
- Glucagon stimulates glycogenolysis and inhibits glycogenesis. It activates a reaction cascade involving cAMP.
- Insulin inhibits glycogenolysis and stimulates glycogenesis. It activates a phosphorylation cascade to inhibit enzymes in glycogenolysis and activate enzymes for glycogenesis.
- Epinephrine is released during stress and promotes glycogenolysis, inhibiting glycogenesis. Increased amounts are released in emergency situations, providing energy for managing the situation.
- Glycogen synthase and glycogen phosphorylase exist in active and inactive conformation, interconverted by covalent modification.
- Phosphorylating enzymes (e.g., phosphorylase kinase) are activated by cAMP, leading to activation of glycogen phosphorylase and inactivation of glycogen synthase.
- Deactivation occurs when phosphoprotein phosphatase reverses these effects, converting the enzymes back to their inactive states.
Hexose Monophosphate Shunt
- The pentose phosphate pathway is an alternative pathway for glucose oxidation. It produces NADPH and ribose-5-phosphate, both essential for various metabolic processes.
- The pathway occurs in the cytoplasm and has two phases: Oxidative and Non-oxidative.
- The oxidative phase is responsible for NADPH production through three key reactions (using glucose-6-phosphate dehydrogenase, gluconolactonase, and 6-phosphogluconate dehydrogenase).
- The non-oxidative phase involves isomerization and condensation of numerous sugar molecules. These reactions utilize transketolase and transaldolase to convert the sugars into intermediates that can enter the glycolytic pathway, producing ribose-5-phosphate and crucial glycolytic intermediates. This phase facilitates the synthesis of aromatic amino acids in some organisms.
Pentose Phosphate Pathway
- An alternative metabolic pathway for glucose oxidation.
- This pathway produces NADPH (reducing agent) and ribose-5-phosphate (component of nucleotides).
- The pathway occurs in two phases (oxidative and non-oxidative).
- The oxidative phase generates NADPH and converts glucose-6-phosphate into ribulose-5-phosphate.
- The non-oxidative phase does not generate ATP but does interconvert sugars (e.g. ribose-5-phosphate, fructose-6-phosphate, and glyceraldehyde-3-phosphate), useful for other pathways.
Regulation of the HMP Shunt
- The pentose phosphate pathway is regulated to meet cellular needs for NADPH and ribose-5-phosphate. It is highly active in cells needing large amounts of NADPH (like red blood cells).
- The oxidative phase is primarily absent in cells that synthesize little lipid (e.g., muscle cells), as these cells have little demand for NADPH.
- G6PD (glucose-6-phosphate dehydrogenase) is a key regulatory enzyme whose activity is affected by NADPH, GSSG, and glucose-6-phosphate.
- Insulin and high-carbohydrate diets stimulate HMP shunt activity by increasing the synthesis of G6PD and 6-phosphogluconate dehydrogenase.
NADPH & Red Blood Cells
- NADPH is important for antioxidant activity in protecting cells from oxidative damage.
- Red blood cells are heavily reliant on the pentose phosphate pathway for NADPH.
- Glutathione peroxidase and glutathione reductase use NADPH to regenerate reduced glutathione, reducing oxidative damage.
- Deficiency of NADPH can lead to increased oxidative stress, resulting in fragile red blood cells and hemolytic anemia. Favism is an example.
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Explore the intricate processes of glycogen metabolism in this comprehensive quiz. Learn how glycogenesis occurs after meals and the role of key hormones like insulin and glucagon in regulating glucose levels. Test your knowledge on the enzymes involved in glycogen synthesis and their functions.
