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Questions and Answers
What is the primary process of converting glucose into glycogen in the fed state?
What is the primary process of converting glucose into glycogen in the fed state?
Which hormones are primarily involved in the hormonal regulation of glycogen metabolism in the fasting state?
Which hormones are primarily involved in the hormonal regulation of glycogen metabolism in the fasting state?
What key metabolic process occurs in muscles during fasting to supply amino acids for gluconeogenesis?
What key metabolic process occurs in muscles during fasting to supply amino acids for gluconeogenesis?
What is the role of the Cori Cycle in the fasting state?
What is the role of the Cori Cycle in the fasting state?
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During the fed state, which of the following is NOT a primary action of the liver?
During the fed state, which of the following is NOT a primary action of the liver?
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What primarily happens to plasma glucose levels during the fasting state?
What primarily happens to plasma glucose levels during the fasting state?
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Which metabolic pathway utilizes carbon skeletons of amino acids?
Which metabolic pathway utilizes carbon skeletons of amino acids?
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In which metabolic state is insulin level high?
In which metabolic state is insulin level high?
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Which process is primarily responsible for generating ATP from NADH?
Which process is primarily responsible for generating ATP from NADH?
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Which of the following is a pathophysiological example related to glycogen metabolism?
Which of the following is a pathophysiological example related to glycogen metabolism?
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What is the primary energy source for the brain?
What is the primary energy source for the brain?
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What enzyme initiates the synthesis of glycogen?
What enzyme initiates the synthesis of glycogen?
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Which substances are required for glycogenesis?
Which substances are required for glycogenesis?
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What bonds connect the glucose units in glycogen?
What bonds connect the glucose units in glycogen?
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Which enzyme is responsible for cleaving the α-1,4 bond in glycogenolysis?
Which enzyme is responsible for cleaving the α-1,4 bond in glycogenolysis?
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Which of the following statements about glycogen branching is true?
Which of the following statements about glycogen branching is true?
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What is generated from glucose-1-phosphate during glycogen synthesis?
What is generated from glucose-1-phosphate during glycogen synthesis?
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Where does glycogenesis primarily occur in the body?
Where does glycogenesis primarily occur in the body?
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What is the main direct product of glycogen breakdown?
What is the main direct product of glycogen breakdown?
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Which enzyme is responsible for converting glucose-1-phosphate to glucose-6-phosphate?
Which enzyme is responsible for converting glucose-1-phosphate to glucose-6-phosphate?
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During fasting states, what happens to glycogen synthesis?
During fasting states, what happens to glycogen synthesis?
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What initiates the process of glycogen breakdown in the presence of low blood sugar?
What initiates the process of glycogen breakdown in the presence of low blood sugar?
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What role does AMP play during glycogenolysis in muscle cells?
What role does AMP play during glycogenolysis in muscle cells?
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Which of the following tissues specifically require glucose?
Which of the following tissues specifically require glucose?
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Which combination accurately describes the effects of insulin on glycogen metabolism?
Which combination accurately describes the effects of insulin on glycogen metabolism?
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What is the primary purpose of gluconeogenesis?
What is the primary purpose of gluconeogenesis?
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What effect does glucose-6-phosphate have on glycogen synthase in the liver?
What effect does glucose-6-phosphate have on glycogen synthase in the liver?
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Which enzyme is involved in both glycolysis and gluconeogenesis?
Which enzyme is involved in both glycolysis and gluconeogenesis?
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Cortisol affects glycogen metabolism how?
Cortisol affects glycogen metabolism how?
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Which substrate is NOT a precursor for gluconeogenesis?
Which substrate is NOT a precursor for gluconeogenesis?
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During the Cori cycle, what is lactate converted into before undergoing gluconeogenesis?
During the Cori cycle, what is lactate converted into before undergoing gluconeogenesis?
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Which statement about Glucose-6-phosphatase is true?
Which statement about Glucose-6-phosphatase is true?
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What hormonal change occurs during exercise that affects glycogen breakdown?
What hormonal change occurs during exercise that affects glycogen breakdown?
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Glycogen Storage Disorders (GSD) result from a deficiency in which of the following?
Glycogen Storage Disorders (GSD) result from a deficiency in which of the following?
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What energy currency is notably consumed during the gluconeogenesis process?
What energy currency is notably consumed during the gluconeogenesis process?
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Which type of condition often results from Glycogen Storage Disorders?
Which type of condition often results from Glycogen Storage Disorders?
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Which of the following tissues specifically requires glucose as a source of energy?
Which of the following tissues specifically requires glucose as a source of energy?
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What is the role of lactate in the Cori cycle?
What is the role of lactate in the Cori cycle?
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Which enzyme is specific to gluconeogenesis and not involved in glycolysis?
Which enzyme is specific to gluconeogenesis and not involved in glycolysis?
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What is a consequence of Glycogen Storage Disorders?
What is a consequence of Glycogen Storage Disorders?
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Which of the following substrates is NOT a precursor for gluconeogenesis?
Which of the following substrates is NOT a precursor for gluconeogenesis?
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What primarily drives the process of gluconeogenesis in the liver?
What primarily drives the process of gluconeogenesis in the liver?
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Which enzyme converts lactate into pyruvate during the Cori cycle?
Which enzyme converts lactate into pyruvate during the Cori cycle?
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What is the main effect of glycogen depletion after 10-18 hours?
What is the main effect of glycogen depletion after 10-18 hours?
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What role does glycogenin play in the synthesis of glycogen?
What role does glycogenin play in the synthesis of glycogen?
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How does branching enzyme facilitate glycogen synthesis?
How does branching enzyme facilitate glycogen synthesis?
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Which of the following best describes the uniqueness of glycogenolysis in muscle tissue?
Which of the following best describes the uniqueness of glycogenolysis in muscle tissue?
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What is a consequence of the dynamic nature of glycogen flux?
What is a consequence of the dynamic nature of glycogen flux?
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What is released when glycogen phosphorylase cleaves an α-1,4 bond in glycogenolysis?
What is released when glycogen phosphorylase cleaves an α-1,4 bond in glycogenolysis?
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Which of the following statements is true regarding glucose preferences in tissues?
Which of the following statements is true regarding glucose preferences in tissues?
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What is the significance of the α-1,6 bonds in glycogen structure?
What is the significance of the α-1,6 bonds in glycogen structure?
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Which process immediately follows the generation of glucose-1-phosphate in glycogenolysis?
Which process immediately follows the generation of glucose-1-phosphate in glycogenolysis?
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Which metabolic process is primarily activated in the liver during the fasting state?
Which metabolic process is primarily activated in the liver during the fasting state?
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Which condition is characterized by a deficiency in glycogen storage and presents as Von Gierke's Disease?
Which condition is characterized by a deficiency in glycogen storage and presents as Von Gierke's Disease?
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What effectively occurs to insulin levels during the transition from fed to fasting states?
What effectively occurs to insulin levels during the transition from fed to fasting states?
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In the context of carbohydrate metabolism, how does adrenaline primarily affect the liver during fasting?
In the context of carbohydrate metabolism, how does adrenaline primarily affect the liver during fasting?
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Which effect does high levels of plasma glucose induce in the fed state?
Which effect does high levels of plasma glucose induce in the fed state?
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During fasting, how does muscle metabolism mainly adapt to support gluconeogenesis?
During fasting, how does muscle metabolism mainly adapt to support gluconeogenesis?
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What is primarily regulated by glucagon in the body during fasting?
What is primarily regulated by glucagon in the body during fasting?
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Which metabolic pathway results in the conversion of pyruvate into glucose?
Which metabolic pathway results in the conversion of pyruvate into glucose?
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What role does the Cori Cycle serve during periods of fasting?
What role does the Cori Cycle serve during periods of fasting?
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What is the primary source of energy for the muscle during fasting?
What is the primary source of energy for the muscle during fasting?
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What is the primary product released from glycogen degradation?
What is the primary product released from glycogen degradation?
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Which enzyme is responsible for transferring the last three glucose residues during glycogenolysis?
Which enzyme is responsible for transferring the last three glucose residues during glycogenolysis?
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In muscle cells, which molecules are known to activate Glycogen Phosphorylase?
In muscle cells, which molecules are known to activate Glycogen Phosphorylase?
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What regulates the activity of protein kinases and phosphatases in glycogen metabolism?
What regulates the activity of protein kinases and phosphatases in glycogen metabolism?
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Which hormone's activity leads to the activation of Glycogen Synthase in the presence of high blood sugar?
Which hormone's activity leads to the activation of Glycogen Synthase in the presence of high blood sugar?
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How does glucagon affect glycogen metabolism in the liver?
How does glucagon affect glycogen metabolism in the liver?
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What effect does glucose-6-phosphate have on Glycogen Phosphorylase in the liver?
What effect does glucose-6-phosphate have on Glycogen Phosphorylase in the liver?
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Which factor does NOT influence allosteric regulation of glycogen metabolism?
Which factor does NOT influence allosteric regulation of glycogen metabolism?
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During strenuous exercise, what is the primary mechanism through which glycogen is mobilized?
During strenuous exercise, what is the primary mechanism through which glycogen is mobilized?
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What is the role of phosphoglucomutase in glycogen metabolism?
What is the role of phosphoglucomutase in glycogen metabolism?
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Study Notes
Post-absorption processing of carbohydrates
- In the fed state, glucose, amino acids, and triglycerides are abundant.
- Insulin increases, and glucagon decreases.
- The liver synthesizes glycogen, triglycerides, and proteins.
- Adipose tissue makes triglycerides.
- Muscle makes glycogen and proteins.
Fasting State
- Blood glucose, amino acids, and triglycerides are reduced.
- Insulin decreases, glucagon and adrenaline increase.
- The liver undergoes glycogenolysis, gluconeogenesis, β-oxidation, and ketogenesis.
- Adipose tissue undergoes lipolysis.
- Muscle undergoes proteolysis, providing amino acids for gluconeogenesis, and uses fatty acids and ketone bodies for fuel.
- Brain utilizes glucose initially, then transitions to using ketone bodies as fuel.
Glycogen
- Glycogen is essential for maintaining blood glucose levels during periods of fasting.
- The brain relies primarily on glucose.
- Red blood cells and other cells lacking mitochondria need glucose.
- Dietary glucose intake is unreliable.
- Glycogen is stored in the liver and muscle as a readily available glucose source.
Glycogen Synthesis
- Glycogen is synthesized from glucose during the fed state.
- The process occurs in the cytosol.
- ATP and uridine triphosphate (UTP) are required for glycogen synthesis.
- Glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase.
- UDP-glucose is synthesized from glucose-1-phosphate.
- UDP-glucose and glycogen are the substrates for glycogen synthase.
- Glycogen synthase elongates glycogen chains by adding UDP-glucose to the non-reducing end.
- Glycogenin initiates glycogen synthesis.
- Branching enzyme adds α-1,6 linkages to glycogen chains, creating branch points.
Glycogen Degradation
- Glycogen phosphorylase breaks down glycogen by cleaving α-1,4 bonds at the non-reducing end.
- Debranching enzyme removes the last three glucose residues from a branch point and transfers them to a non-reducing end.
- It also releases free glucose from α-1,6 bonds.
- The main product of glycogen breakdown is glucose-1-phosphate.
- Muscle cells lack glucose-6-phosphatase and cannot release glucose to the bloodstream.
Allosteric Regulation of Glycogen Metabolism
- Glucose-6-phosphate activates glycogen synthase and inhibits glycogen phosphorylase in the liver.
- Calcium and AMP activate glycogen phosphorylase in muscle.
Hormonal Regulation of Glycogen Metabolism:
-
Glucagon:
- Secreted by the pancreas in response to low blood glucose.
- Binds to receptors on the liver, activating protein kinase A and inhibiting protein phosphatase 1.
- This process promotes glycogen breakdown and glucose release by activating glycogen phosphorylase and inhibiting glycogen synthase.
-
Adrenaline:
- Secreted by the adrenal glands during exercise.
- Binds to α-adrenoreceptors, activating protein kinase A and inhibiting protein phosphatase 1.
- This process promotes glycogen breakdown in both the liver and muscle.
-
Insulin:
- Secreted by the pancreas in response to high blood glucose.
- Binds to receptors on the liver and muscle, activating protein phosphatase 1.
- This process promotes glycogen synthesis by activating glycogen synthase and inhibiting glycogen phosphorylase.
Gluconeogenesis
- Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources, such as lactate, glycerol, or amino acids.
- It is essentially a reversal of glycolysis, but involves different enzymes at irreversible steps.
- Pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase, and glucose-6-phosphatase are critical enzymes involved in gluconeogenesis.
- Gluconeogenesis requires energy in the form of ATP.
The Cori Cycle
- Lactate produced during muscle metabolism is transported to the liver.
- In the liver, lactate is converted to pyruvate.
- Pyruvate undergoes gluconeogenesis to produce glucose.
- Glucose is released back into the bloodstream and used by muscle.
Glycogen Storage Disorders (GSDs)
- GSDs are a group of inherited metabolic disorders due to deficiencies in enzymes involved in glycogen synthesis or breakdown.
- These disorders result in chronic hypoglycemia, enlarged liver, muscle fatigue, and cramps.
- There are 12 known types of GSD, with varying severity depending on the affected enzyme and its tissue location.
Learning Objectives
- Understand glycogen metabolism in fed and fasting states
- Describe the hormonal control of glycogen by insulin, glucagon, and catecholamines
- Explain the Cori Cycle and its function in the fasting state
- Understand the role of gluconeogenesis in maintaining blood glucose levels
- Describe a pathophysiological example of glycogen storage disorders: Von Gierke's Disease
Carbohydrate Metabolism
- Glycogen synthesis: creation of glycogen from glucose
- Glycogenolysis: breakdown of glycogen into glucose
- Gluconeogenesis: synthesis of glucose from non-carbohydrate sources (like amino acid carbon skeletons)
- Glycolysis: breakdown of glucose into pyruvate
- Acetyl-CoA: product of glycolysis, used in the Krebs cycle
- Krebs cycle: conversion of Acetyl-CoA to carbon dioxide, water, and NADH
- Oxidative phosphorylation: energy from NADH is extracted to produce ATP
Fed and Fasting States
- Fed State:
- High levels of plasma glucose, amino acids, and triglycerides
- Insulin increases, glucagon decreases
- Liver, adipose tissue, and muscle store nutrients
- Fasting State:
- Reduced levels of plasma glucose, amino acids, and triglycerides
- Insulin decreases, glucagon and adrenaline increase
- Liver: glycogenolysis, gluconeogenesis, beta-oxidation, ketogenesis
- Adipose tissue: lipolysis
- Muscle: protein breakdown for gluconeogenesis, uses fatty acids and ketone bodies as fuel; does not release glucose into the bloodstream
- Brain uses glucose and ketone bodies as fuel
Glycogen
- Key source of blood glucose, essential for life
- Brain mainly uses glucose for fuel, as well as cells without mitochondria
- Dietary glucose intake is unreliable
- Glycogen: stored form of readily mobilized glucose
- Primarily located in liver (100g) and muscle (400g)
Glycogen Structure
- A homopolymer of glucose
- Units linked by alpha-1,4 and alpha-1,6 glycosidic bonds
Glycogen Synthesis (Glycogenesis)
- Occurs in the cytosol
- Requires ATP and UTP
- Glucose is converted to glucose-6-phosphate
- Glucose-1-phosphate is generated from glucose-6-phosphate
- UDP-glucose is synthesised from glucose-1-phosphate
- UDP-glucose and glycogen are substrates for glycogen synthase
- Glycogen synthase creates alpha-1,4 linkages
- Cannot initiate chains, only elongate them
- Protein glycogenin initiates chains, adds the first glucose to a tyrosine residue
- Glycogenin catalyses the transfer of the first few glucose molecules
- Branching enzyme creates alpha-1,6 bonds, increasing the number of non-reducing ends for glycogen synthase
Glycogenolysis
- Glycogen phosphorylase breaks alpha-1,4 bonds, generating glucose-1-phosphate
- Debranching enzyme:
- Oligoglucan transferase removes the last 3 residues and transfers them to a non-reducing end.
- Amylo-alpha-(1,6) glucosidase releases free glucose from the alpha-1,6 bond.
- Main product of glycogen breakdown: glucose-1-phosphate
- Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate
- Glucose-6-phosphate translocase moves glucose-6-phosphate into the ER
- Glucose-6-phosphatase releases free glucose in the ER (in liver)
- Muscle cells lack glucose-6-phosphatase and cannot release glucose into blood
Regulation of Glycogen Metabolism
- Determined by the energy requirements of the cell
- Fed state: increased synthesis, decreased degradation
- Fasting state: decreased synthesis, increased degradation
- Main points of regulation: glycogen synthase and glycogen phosphorylase
- Regulation mechanisms:
- Allosteric regulation: molecules directly bind and alter enzyme activity
- Hormonal regulation: modulation of enzyme activity through phosphorylation/dephosphorylation by protein kinases and phosphatases
Allosteric Regulation of Glycogen Synthesis
- Liver:
- Glucose-6-phosphate activates glycogen synthase
- Glucose-6-phosphate inhibits glycogen phosphorylase
- Muscle:
- Ca2+ (released during muscle contraction) and AMP (generated by ATP depletion) activate glycogen phosphorylase
Hormonal Regulation of Glycogen Synthesis
-
Allosteric regulation: molecules directly bind and alter enzyme activity
-
Hormonal regulation: modulation of enzyme activity through phosphorylation/dephosphorylation by protein kinases and phosphatases
-
Protein kinases: phosphorylate proteins
-
Protein phosphatases: dephosphorylate proteins
-
Phosphorylation generally inactivates glycogen synthase, activates glycogen phosphorylase (promoting breakdown)
-
Dephosphorylation generally activates glycogen synthase, inactivates glycogen phosphorylase (promoting synthesis)
-
Glucagon:
- Secreted by pancreas when blood sugar is low (fasting)
- Binds glucagon receptors (GsPCR) in the liver
- Activates protein kinase A and inactivates protein phosphatase 1
- Increases glycogen breakdown and glucose release
-
Adrenaline:
- Released from adrenal glands during exercise
- Binds alpha-adrenoreceptors (GsPCR) in liver or muscle
- Activates protein kinase A and inactivates protein phosphatase 1
- Increases glycogen breakdown and glucose release
-
Insulin:
- Secreted by pancreas when blood sugar is high (fed)
- Binds insulin receptors (RTK) in liver and muscle
- Activates protein phosphatase 1
- Increases glycogen synthesis (glucose storage)
-
Cortisol:
- Has mixed effects: increases glycogen synthesis in the liver and promotes breakdown in muscle
Glucose Utilization and Glycogen Depletion
- Glycogen stores are finite
- Some tissues require glucose (RBCs, brain, testes, lens)
- Glycogen stores last 10-18 hours
- When glycogen is depleted, glucose needs to be produced from other sources (gluconeogenesis)
Gluconeogenesis
- Can be seen as a reverse of glycolysis
- Many enzymes are shared with glycolysis
- Differences in irreversible steps of glycolysis:
- Pyruvate carboxylase and PEP carboxykinase replace pyruvate kinase
- Fructose-1,6-bisphosphatase replaces phosphofructokinase
- Glucose-6-phosphatase (in ER) and G6P translocase replace hexokinase and glucokinase
- Gluconeogenesis requires energy (2 ATP per glucose molecule)
Substrates for Gluconeogenesis
- Lactate: released by exercising muscle, involved in the Cori cycle
- Glycerol: from fat stores (triglycerides)
- Amino acids: from tissue protein breakdown
Cori Cycle
- Also known as the lactic acid cycle
- Metabolizes lactate into glucose
- Steps:
- Lactate transported from muscle to the liver through the blood
- Lactate converted to pyruvate by lactate dehydrogenase
- Pyruvate used in gluconeogenesis to produce glucose
- Glucose released back into the blood, taken up by muscles
Glycogen Storage Disorders (GSD)
- Inherited metabolic disorders caused by deficiencies in enzymes needed for glycogen synthesis or breakdown
- Result in chronic hypoglycemia, enlarged liver, muscle fatigue, cramps
- 12 types (I-XII) with varying severity depending on the affected enzyme and its tissue distribution
- Can involve the liver, muscles, or both
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Description
This quiz covers the metabolic processes that occur after carbohydrate absorption, including the roles of insulin and glucagon during the fed and fasting states. It explores glycogen synthesis, lipolysis, and energy utilization in various tissues such as liver, muscle, and adipose tissue. Test your understanding of these crucial biochemical processes.
