Glycogen Metabolism 10 Flashcards
What is glycogen metabolism
What is the structure of glycogen
How is cytoplasmic NADH transported to the mitochondria
Formation of Malate or Glycerol-3-Phosphate: In the cytoplasm, NADH transfers its electrons to either oxaloacetate or dihydroxyacetone phosphate, forming malate or glycerol-3-phosphate, respectively. This step is catalyzed by cytoplasmic enzymes such as malate dehydrogenase or glycerol-3-phosphate dehydrogenase.
Shuttling Across the Mitochondrial Membrane:
Malate Shuttle: In many tissues, such as liver and kidney cells, malate formed in the cytoplasm is transported into the mitochondria by the malate shuttle system. Malate enters the mitochondria via a malate-alpha-ketoglutarate antiporter located in the inner mitochondrial membrane. Once inside the mitochondria, malate is converted back to oxaloacetate by mitochondrial malate dehydrogenase, regenerating NADH in the mitochondrial matrix.
Glycerol-3-Phosphate Shuttle: In some tissues, such as skeletal muscle and brain cells, glycerol-3-phosphate formed in the cytoplasm is transported into the mitochondria by the glycerol-3-phosphate shuttle system. Glycerol-3-phosphate enters the mitochondria via a glycerol-3-phosphate transporter located in the inner mitochondrial membrane. Once inside the mitochondria, glycerol-3-phosphate is oxidized back to dihydroxyacetone phosphate by mitochondrial glycerol-3-phosphate dehydrogenase, regenerating NADH in the mitochondrial matrix.
Oxidative Phosphorylation: Once NADH is regenerated in the mitochondrial matrix, it participates in oxidative phosphorylation, the process by which ATP is generated through the electron transport chain (ETC) and ATP synthase. NADH donates its electrons to the ETC, leading to the pumping of protons across the inner mitochondrial membrane and the generation of a proton gradient. This gradient drives ATP synthesis by ATP synthase.
How is glycogen synthesised
Glucose Uptake: Glucose enters the cells through glucose transporters, primarily facilitated by insulin signaling in the liver and muscles. Glucose can be derived from dietary carbohydrates or from the breakdown of glycogen stores.
Formation of Glucose-6-Phosphate: Once inside the cell, glucose is phosphorylated by hexokinase to form glucose-6-phosphate (G6P). This step traps glucose within the cell, preventing it from diffusing out and maintaining a concentration gradient for further glucose uptake.
Conversion to Glucose-1-Phosphate: Glucose-6-phosphate is converted to glucose-1-phosphate (G1P) by the enzyme phosphoglucomutase (PGM). This conversion involves an isomerization reaction in which the phosphate group is relocated from the sixth carbon to the first carbon of the glucose molecule.
Activation of Glucose: Glucose-1-phosphate is then activated by the addition of a uridine diphosphate (UDP) molecule, forming UDP-glucose. This reaction is catalyzed by the enzyme UDP-glucose pyrophosphorylase, and it serves to activate glucose for incorporation into the growing glycogen chain.
Branching of glycogen chain
Glycogen Chain Elongation: Glycogen synthase is the enzyme responsible for catalyzing the formation of the α-1,4-glycosidic bonds that link glucose molecules together to form the linear glycogen chain. UDP-glucose acts as the donor of glucose units during this process.
How does branching work in glycogen synthesis
Branching: As the glycogen chain elongates, branching occurs through the action of the enzyme branching enzyme (glycogen branching enzyme or amylo-α-1,4→α-1,6-transglucosidase). This enzyme cleaves a segment of the growing glycogen chain and transfers it to a neighboring chain, forming a branch point.
How is glycogen synthesis initiated
How is glycogen broken down
Glycogen Breakdown: Once activated, glycogen phosphorylase catalyzes the cleavage of α-1,4-glycosidic bonds in the glycogen molecule, releasing glucose-1-phosphate units from the non-reducing ends of the glycogen chains. This process continues until the glycogen molecule is extensively degraded.
Debranching of glycogen
Release of Glucose: Glucose-1-phosphate produced by glycogen phosphorylase is converted to glucose-6-phosphate by phosphoglucomutase. Glucose-6-phosphate is then converted to free glucose by glucose-6-phosphatase in the liver or released directly into the bloodstream in muscle cells.
How does glycogen debranching work
Debranching Enzyme Action: As glycogen phosphorylase approaches a branch point in the glycogen molecule, it encounters α-1,6-glycosidic bonds. These bonds cannot be directly cleaved by glycogen phosphorylase. Instead, the debranching enzyme complex is responsible for removing the remaining glucose residues at the branch points. The debranching enzyme consists of two activities: transferase and α-1,6-glucosidase. The transferase activity transfers a block of three glucose residues from the branch point to the non-reducing end of another glycogen chain, leaving a single glucose residue at the branch point. The α-1,6-glucosidase activity then hydrolyzes this remaining glucose residue, releasing free glucose.
What is the fate of glucose-1-phosphate
glucose-1-phosphate serves as a key intermediate in cellular metabolism, contributing to energy production, glucose homeostasis, and the synthesis of important biomolecules such as glycogen and nucleotides
What are the characteristics of glycogen phosphorylase
When is glucagon released
When is insulin released
How is glycogen phosphorylase allosterically regulated
How us liver glycogen phosphorylase allosterically regulated
What receptor does insulin act on