MCAT Biochemistry
Glycogen regulation revolves around two key enzymes: glycogen synthase, which catalyzes the rate-limiting step during glycogen synthesis, and glycogen phosphorylase, the enzyme responsible for the rate-limiting step during glycogen degradation. The hormones insulin, glucagon, and epinephrine play significant roles in regulating these enzymes. Insulin promotes glycogen synthesis by activating a series of proteins, such as tyrosine kinase, IRS-1, PI3K, and protein phosphatase. On the other hand, glucagon promotes glycogenolysis by triggering the activation of adenylate cyclase, cyclic AMP, and protein kinase A.
Epinephrine, produced in response to stress, has a dual role in promoting glycogenolysis. By binding to the beta receptors on hepatocytes and skeletal muscle, it activates the same signal pathway as glucagon. Alternatively, it binds to alpha receptors on hepatocytes, resulting in activation of phospholipase C or PLC, which in turn cleaves PIP2 to IP3 and DAG. This leads to the release of calcium into the cytosol, activation of glycogen phosphorylase kinase, and glycogen phosphorylase. Overall, the concerted actions of these hormones help maintain glucose homeostasis in the body.
Lesson Outline
<ul> <li>Glycogen Synthesis and Degradation</li> <ul> <li>Glycogen synthase: rate-limiting enzyme during glycogen synthesis</li> <li>Glycogen phosphorylase: rate-limiting enzyme during glycogen degradation</li> <li>Hormones controlling glycogen: insulin, glucagon, and epinephrine</li> </ul> <li>Insulin and its effects</li> <ul> <li>Anabolic hormone, promotes synthesis</li> <li>Facilitates glucose absorption</li> <li>Effects of insulin on cells</li> <ul> <li>Insulin binds its receptor → activation of tyrosine kinase domains</li> <li>Tyrosine kinase auto-phosphorylates tyrosine residues (cytoplasmic side of the receptor), activates insulin receptor substrate-1 (IRS-1) by phosphorylation</li> <li>IRS activates protein phosphatase (via an intermediate, PI3K)</li> <li>Direct and indirect activation of glycogen synthase</li> </ul> <li>Role of cortisol and glucose-6-phosphate</li> </ul> <li>Glucagon and its effects</li> <ul> <li>Antagonist to insulin</li> <li>Glucagon binds its receptor → activation of adenylate cyclase → ↑ cAMP → ↑ protein kinase A</li> <li>PKA inactivates glycogen synthase by phosphorylation → ↓ glycogenesis</li> <li>PKA activates glycogen phosphorylase kinase by phosphorylation</li> <li>Glycogen phosphorylase kinase activates glycogen phosphorylase by phosphorylation → ↑ glycogenolysis</li> </ul> <li>Epinephrine and its effects</li> <ul> <li>Role in stress response</li> <li>Epinephrine promotes glycogenolysis in the liver and skeletal muscle</li> <li>Epinephrine binds the beta receptor (liver and skeletal muscle) to activate the cAMP pathway</li> <li>Epinephrine binds the alpha receptor on hepatocytes to activate the IP3/DAG pathway</li> <li>Epinephrine binds the alpha receptor on hepatocytes to activate phospholipase c → PIP2 breaking into IP3 + DAG → ↑ calcium (released from endoplasmic reticulum)</li> <li>Different signal transduction pathways</li> <li>Calcium binds to calmodulin to form calcium-calmodulin complex → ↑ glycogen phosphorylase kinase → ↑ glycogen phosphorylase → ↑ glycogenolysis</li> <li>AMP activates glycogen phosphorylase</li> </ul> </ul>
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FAQs
Insulin is an important hormone that promotes glycogen synthesis and suppresses glycogen degradation. It does this by activating the insulin receptor, leading to the activation of protein phosphatase. Protein phosphatase then dephosphorylates glycogen synthase, activating it, which promotes glycogen synthesis. Meanwhile, protein phosphatase also dephosphorylates glycogen phosphorylase, inactivating it and preventing glycogen degradation. This helps maintain blood glucose levels within a normal range.
Glucagon is a hormone that opposes the action of insulin, promoting glycogen degradation and inhibiting glycogen synthesis. It does this by activating glycogen phosphorylase, leading to the breakdown of glycogen into glucose-1-phosphate, which is then converted into glucose-6-phosphate and ultimately released as glucose. This process increases blood glucose levels, providing energy during times of low glucose availability, such as fasting or prolonged exercise.
Epinephrine, also known as adrenaline, plays a significant role in glycogen regulation during periods of stress or high energy demands. It promotes glycogen degradation by activating glycogen phosphorylase, similar to glucagon. Additionally, epinephrine stimulates the release of glucose from the liver and inhibits glycogen synthesis, ensuring a rapid response to increased energy needs. This helps the body maintain a sufficient supply of glucose for energy during physical activity or stress.
Glycogen synthase and glycogen phosphorylase are key enzymes in glycogen regulation. Glycogen synthase catalyzes the synthesis of glycogen by adding glucose residues to the existing glycogen molecule. This enzyme is activated by dephosphorylation, which is stimulated by insulin. Glycogen phosphorylase, on the other hand, breaks down glycogen into glucose-1-phosphate by cleaving the α-1,4 glycosidic bonds. Its activation occurs through phosphorylation, which is stimulated by glucagon and epinephrine.
