Chapter 25 Glycogen Synthesis

Flashcards covering the vocabulary and key concepts from the lecture notes on Glycogen Synthesis.

Glycogen Degradation

Yields glucose 1-phosphate.

UDP-glucose

The monomer that is used to extend the glycogen chain in synthesis; an activated form of glucose.

UDP-glucose Pyrophosphorylase

Synthesizes UDP-glucose; the reaction is subsequently rendered irreversible by the hydrolysis of pyrophosphate.

Glycogen Synthase

Key regulatory enzyme in glycogen synthesis that transfers a glucose moiety from UDP-glucose to the C-4 terminal residue of a glycogen chain to form an α-1,4-glycosidic bond. It requires an oligosaccharide of glucose residues as a primer.

Glycogenin

A dimer of two identical subunits that synthesizes the primer required by glycogen synthase. Each subunit generates an oligosaccharide of glucose residues 10–20 glucosyl units long.

Branching Enzyme

Generates branches by cleaving an α-1,4-linkage and taking a block of approximately seven glucoses and synthesizing an α-1,6-linkage.

ATP and Glycogen Synthesis

Only two molecules of ATP are required to incorporate dietary glucose into glycogen, while the complete oxidation of glucose derived from glycogen yields 31 molecules of ATP.

G Subunit (GL in liver and GM in muscle)

A key regulatory subunit of protein phosphatase 1 (PP1) that binds glycogen and the catalytic subunit of PP1, localizing the enzyme with its substrates.

Insulin's effect on Glycogen Synthase Kinase

Insulin stimulates glycogen synthesis by activating a signal transduction pathway that results in the phosphorylation and inactivation of glycogen synthase kinase.

Fatty Liver

Excessive ethanol consumption disrupts lipid metabolism in the liver, resulting in triacylglycerol accumulation

Branching Enzyme Deficiency

Results in glycogen with fewer branch points. This is suggested by a high ratio of glucose 1-phosphate to free glucose (much higher than 12) after glycogen degradation.

Phosphorylase Kinase

Activates glycogen phosphorylase by phosphorylating it.

Role of Insulin in Glycogen Synthesis

Insulin promotes glycogen synthesis by activating protein phosphatase 1 (PP1), which dephosphorylates glycogen synthase b, converting it to the more active a form.

Von Gierke's Disease (Type Ia)

A glycogen storage disease caused by a deficiency in glucose-6-phosphatase, leading to the accumulation of glycogen in the liver and kidneys, and resulting in hypoglycemia.

Regulation of Glycogen Phosphorylase

Glycogen phosphorylase is allosterically regulated by AMP (activator) and ATP/glucose-6-phosphate (inhibitors) in muscle. In the liver, it is primarily regulated by glucose.

Glycogen Synthase (Regulation)

Usually inactive when in the phosphorylated b form and usually active when in the unphosphorylated a form. The key regulatory process is the conversion of the b form in the T state to the active R state of the b form by binding glucose 6-phosphate.

Glycogen Synthesis Regulation

Inhibited by the same glucagon and epinephrine signaling pathways that stimulate glycogen breakdown. Phosphorylation of glycogen synthase by protein kinase A to form glycogen synthase b inhibits glycogen synthesis. Glycogen synthase kinase also phosphorylates and inhibits glycogen synthase.

Protein Phosphatase 1 (PP1)

Shifts glycogen metabolism from the degradation mode to the synthesis mode by removing phosphoryl groups from glycogen synthase b (converting it into the more active a form) and from phosphorylase kinase and phosphorylase a (inhibiting glycogen degradation).

Liver-Glycogen Metabolism Regulation

Glycogen degradation in the liver is inhibited and glycogen synthesis is stimulated by high blood-glucose levels. The conversion of glycogen phosphorylase a from the R state to the T state by the binding of glucose results in the activation of PP1 that is associated with the phosphorylase.

Diabetes Mellitus

Characterized by the presence of excess glucose and underutilization of the fuel. In type 1 diabetes, insulin is not produced. In type 2 diabetes, insulin is produced but the insulin-signaling pathway is not responsive, a condition referred to as insulin resistance.

Glycogen Storage Diseases

Genetic diseases characterized by the accumulation of abnormal amounts or types of glycogen in cells, often due to defects in enzymes involved in glycogen metabolism.

McArdle's Disease (Type V)

A glycogen storage disease resulting from a deficiency in muscle glycogen phosphorylase, causing exercise-induced muscle pain, cramps, and fatigue.

Cori Cycle

A metabolic pathway in which lactate produced by anaerobic glycolysis in muscles is transported to the liver and converted back to glucose via gluconeogenesis.

Debranching Enzyme

Enzyme that debranches glycogen by transferring a limit branch to another branch and hydrolyzing the α-1,6-glycosidic bond.

Glycogen Phosphorylase a

A form of glycogen phosphorylase activated by phosphorylation, promoting glycogen breakdown.

Glycogen Phosphorylase b

The unphosphorylated, less active form of glycogen phosphorylase.

Glucagon

Hormone that stimulates glycogen breakdown in the liver to increase blood glucose levels.

Epinephrine

A hormone released from the adrenal medulla that stimulates glycogen breakdown in muscles and the liver as part of the fight-or-flight response.

Glycogen Targeting Protein

A protein that targets glycogen phosphorylase and glycogen synthase to glycogen particles.

Cori's Disease

A glycogen storage disease (Type III) resulting from a deficiency in debranching enzyme, leading to the accumulation of limit dextrin structures in glycogen.

Hers' Disease

A glycogen storage disease (Type VI) caused by a deficiency in liver phosphorylase, resulting in mild hypoglycemia.

Hyp

A condition characterized by low blood glucose levels, often resulting from excessive insulin production or glycogen storage diseases.