Glycogen Metabolism and Disorders Quiz

Glucose and Glycogen Regulation

• Glucose levels in the blood (glycemia) are tightly controlled through various processes that produce or consume glucose.
• Excess glucose is stored as glycogen, which is released when needed to maintain normal blood glucose levels.

Glucose Dynamics in Living Organisms

• Key processes involved in glucose regulation include glycogenesis, glycogenolysis, glycolysis, and gluconeogenesis.
• Glycogen is a branched polymer of glucose, stored primarily in the liver and skeletal muscles.

Glycogen Degradation

• Glycogen degradation involves removing glucose residues from the non-reducing end of the glycogen molecule through phosphorolysis.
• Glycogen phosphorylase catalyzes the breakdown of glycogen.
• A debranching enzyme is also needed for complete glycogen breakdown.

Glycogen Degradation: Debranching

• The debranching process involves two steps:

  • Transferase activity: moves a block of oligoglucose from a branched point to a linear chain
  • α(1→6) glucosidase activity: hydrolyzes the remaining α1→6 linked glucose.

• Outcome of debranching is glucose-1-phosphate.

Glycogen Degradation and Regulation of Glucose Level

• Glucose-1-phosphate is converted to glucose-6-phosphate.
• Glucose-6-phosphate can undergo glycolysis, the pentose pathway, or gluconeogenesis.
• Gluconeogenesis regenerates glucose using glucose-6-phosphatase, primarily in liver and kidney cells.
• Muscle and adipose tissue lack glucose-6-phosphatase.

Glycogen Storage Diseases

• Several diseases are possible from glycogen breakdown issue due to various enzyme deficiencies.
• Acid maltase (α(1,4)-glucosidase) deficiency is known as Pompe disease.
• McArdle syndrome is caused by a deficiency in glycogen phosphorylase in muscle tissue.
• Von Gierke disease is the most common glycogen storage disease, caused by glucose-6-phosphatase deficiency.

Glucose 6-Phosphatase Deficiency: Von Gierke Disease

• Von Gierke disease is characterized by glucose-6-phosphatase deficiency.
• Symptoms include fasting hypoglycemia, fatty liver, hepatomegaly, and other issues.
• Treatment often includes frequent glucose administration.

Glycogen Synthesis

• Glucose-6-phosphate is converted to glucose-1-phosphate for glycogen storage synthesis.
• Glycogenin initiates glycogen synthesis by attaching glucose units.

Glycogen Synthesis: Chain Elongation

• UDP-glucose is used as a precursor for glucose attachment to the growing glycogen chain.
• Glycogen synthase catalyzes the elongation process.

Glycogen Synthesis: Branching

• Glycogen branching enzyme creates α(1→6) linkages, making the glycogen molecule more branched.

Glycogen Synthesis Priming

• Glycogenin starts the polymerization.

Regulation of Metabolic Pathways

• Cells and organisms maintain a dynamic steady state.
• Enzyme activity is regulated by various factors, including association with regulatory proteins and compartmentation.

Covalent Modifications of Enzymes

• Phosphorylation/dephosphorylation are common means of enzyme regulation, modifying their activity.
• Kinases add phosphate groups, while phosphatases remove them.

Assessment of Individual Enzyme Contribution to a Pathway

• The contribution of each enzyme to the metabolic flux can be determined experimentally.

Coordinated Regulation of Glycolysis and Gluconeogenesis

• Coordinated regulation between glycolysis and gluconeogenesis is critical.
• Regulation is achieved at the level of the three exergonic steps in both pathways.
• F-2,6-BP is a key regulator.

Regulation of Glycolysis at Hexokinase Level

• Important isozymes, hexokinase IV (glucokinase), have distinctive features.
• Different isozymes have varying Km, Vmax and regulation mechanisms.
• Glucokinase is not inhibited by glucose-6-phosphate.

Hexokinase Isozyme Regulation

• Isozymes I-III have low Km and are inhibited by glucose-6-phosphate, functioning primarily in muscle tissue.
• Glucokinase activity increases with increasing blood glucose to regulate its uptake.

Regulation of Glycolysis at PFK Level

• This is the key regulatory step in glycolysis.
• PFK-1 is allosterically regulated by ATP, and enhanced by citrate.
• Lower ATP stimulates PFK-1 activity.

Regulation of Glycolysis at Pyruvate Kinase Level

• Pyruvate kinase is allosterically regulated by ATP, acetyl-CoA, fatty acids and alanine.
• A cAMP-dependent protein kinase (PKA) phosphorylates Pyruvate kinase (liver) inhibiting it.

Coordinated Regulation of Gluconeogenesis

• Pyruvate carboxylase is regulated allosterically by acetyl-CoA.

Coordinated Regulation of Glycolysis and Gluconeogenesis

• ATP and citrate inhibit glycolysis.
• ADP and AMP activate glycolysis and inhibit gluconeogenesis.
• Fructose 2,6-bisphosphate is an important regulator

Fructose 2,6-bisphosphate

• Fructose 2,6-bisphosphate is an allosteric regulator of PFK-1 (glycolysis) and FBPase-1 (gluconeogenesis).
• High levels of F2,6-BP activates PFK-1 and inhibits FBPase-1.

PFK-2/FBPase-2

• The PFK-2/FBPase-2 regulates F26BP levels and thus influences glycolysis and gluconeogenesis.
• Insulin stimulates its kinase activity, while glucagon stimulates the phosphatase activities.

Coordinated Regulation at the level of F6P/F1,6bisP: overview

• Shows the regulation by allosteric effectors of the enzymes at the glycolysis/gluconeogenesis junction and the role of cAMP and hormones.

Coordinated regulation of glycogen synthesis and breakdown: Control of glycogen breakdown

• Glycogen phosphorylase exists in two forms; a (active) and b (less active).
• Phosphorylation (by phosphorylase kinase) transforms phosphorylase b into phosphorylase a.

Coordinated regulation of glycogen synthesis and breakdown: Control of glycogen synthesis

• Glycogen synthase exists as a (active) and b (less active) forms.
• Activation of Glycogen synthase b (inactive) is catalyzed by PP1 (phosphatase).
• Glycogen synthesis and breakdown are reciprocally regulated.

Control of glycogen synthesis from blood glucose in myocytes

• GLUT4 translocation to the plasma membrane facilitates glucose uptake in muscle cells upon insulin signaling.
• Hexokinase, once stimulated properly, begins phosphorylation and subsequent steps towards glycogen synthesis.

Carbohydrate Regulation in Liver Cells (Overview)

• Insulin and glucagon have antagonistic effects on carbohydrate metabolism in liver cells.
• Insulin promotes glycogen synthesis and inhibits glycogen breakdown.
• Glucagon promotes glycogen breakdown and inhibits glycogen synthesis and activates gluconeogenesis.

Hormones and Their Effects

• Specific hormones regulate pathways by impacting enzyme activity in different cells.
• Insulin promotes glycogen synthesis and inhibits glycogen breakdown.
• Glucagon promotes glycogen breakdown and inhibits glycogen synthesis.

Differences in Carbohydrate Metabolism in Liver and Muscles

• These are distinct (different) processes in terms of their regulation, especially in terms of the availability of glucose.
• Muscle cells do not produce blood glucose, therefore they do not need a blood glucose regulatory system (phosphatase).

Effects of Insulin

• Insulin inhibits cAMP-dependent protein kinase (PKA)
• Insulin stimulates glycogen synthesis
• Insulin inhibits glycogen degradation
• Insulin stimulates phosphoprotein phosphatase

Effects of Glucagon, Epinephrine and Insulin

• These hormones have different effects on liver and muscle cells' carbohydrate metabolism.
• Glucagon and epinephrine promote glycogen breakdown.
• Insulin promotes glycogen synthesis.

Metabolic Characteristics of Glycolysis

• Glycolysis occurs in several stages and is influenced by different factors & metabolites (NADH, Lactate, etc...).

Drugs and diseases

• Certain diseases can be caused by issues in glycogen metabolism or hormone regulation.
• Some drugs can enhance specific biochemical reactions and/or help with disease management.

Test your knowledge on glycogen metabolism, storage, and related diseases with this comprehensive quiz. Explore the biochemical pathways, enzyme functions, and clinical implications associated with glycogen in the human body. Perfect for students studying biochemistry or related fields.