Glycogen Metabolism Flashcards
Explain the process of glycogen breakdown including the enzymes involved
Glycogen phosphorylase catalyzes the breakage of a1-4 glycosidic bonds between glucose residues (linear chains), releasing a glucose 1-phosphate molecule.
Glycogen debranching enzyme is responsible for transferring glucose residues near an a1-6 branch to create a linear chain. Four residues before the branch where the three first residues are transferred to the linear chain, and the last residue is released as a free glucose molecule.
What are the fates of Glu1P from glycogen breakdown?
Glu1P can either enter the glycolysis for energy production, or enter the liver to replenish blood glucose levels.
In the liver Glu1P is converted to Glu6P by phosphoglucomutase through the intermediate Glu1,6BP. Glu6P is then hydrolyzed to glucose and inorganic phosphate by glucose 6-phosphatase in the ER lumen. The molecules can then re-enter the cytosol, and glucose can enter the blood stream.
Explain the steps of glycogen synthesis and the enzymes involved
Glycogenin forms a primer for the glycogen chain. The tyrosin residue of glycogenin forms an initial glycogen chain/primer by glucose-donations from UDP-glucose. The initial chain (of 7 glucose residues) is further elongated by glycogen synthase and UDP-glucose. Glycogen-branching enzyme forms branching points of the chain, and new reducing ends that are elongated by glycogen synthase.
What hormones are important for regulating the glycogen synthesis and breakdown?
Glucagon, insulin, and epinephrine.
What enzymes are directly involved in regulation of glycogen-regulating enymes and what are their function?
(Glycogen) phosphorylase kinase phosphorylates glycogen phosphorlyase b, activating it (conformational change to glycogen phosphorylase a), stimulating glycogen breakdown.
Phosphoprotein phosphatase 1 (PP1) dephosphorylates glycogen phophorylase a, deactivating it (to glycogen phosphatase b).
PP1 also promotes activation of glycogen synthase by removing the phosphate groups.
Glycogen synthase kinase 3 (GSK3) phosphorylates glycogen synthase a (active) at three Ser residues to glycogen synthase b (inactive).
Casein kinase II (CKII) primes the glycogen synthase by phosphorylation before the activity of GSK3.
AMP-activated protein kinase (AMPK) also phosphorylates glycogen synthase a and inactivates it.
Connect the different regulatory enzymes to the different hormone signals (insulin, glucagon, epinephrine)
Insulin:
Inhibits glycogen synthase kinase 1 (GSK1) favouring the unphosphorylated (active) form of glycogen synthase (b).
Activates phosphoprotein phosphatase 1 (PP1), dephosphorylating (activating) the phosphorylated (inactive) glycogen synthase (b).
Epinephrine:
Epi promotes an increase of glycogen breakdown by, ultimately, activating glycogen phosphorylase and deactivating phosphoprotein phosphatase 1 (PP1).
Glucagon:
Works similarly in liver as epinephrine in muscle. Leads to activation of glycogen phosphorylase and inactivation of PP1 through GPCR and PKA. Inactivates glycogen synthase by phosphorylation.
Name the three ketone bodies, start and endpoint of their synthetic pathways and the enzymes involved
Acetone, acetoacetyl, and (beta-)hydroxybutarate.
Two acetyl-CoA are condenced to acetoacetyl-CoA by thiolase.
Acetoacetyl-CoA is converted to acetoacetyl through two steps catalyzed by HMG-CoA synthase and HMG-CoA lyase, respectively.
Acetoacetyl is converted either to acetone by acetoacetate decarboxylase, or to hydroxybutarate by (D-beta-)hydroxybutarate dehydrogenase.
Explain the effects of starvation/low calorie diets on the citric acid cycle and ketone body formation
Starvation and low glucose levels lead to oxidation of fatty acids and the formation of acetyl-CoA. These conditions slow the citric acid cycle by promoting gluconeogenesis and production of glucose for fuel. Depletion of citric acid cycle intermediates pushes acetyl-CoA to keton body production.
a-CoA from fatty acid oxidation is used in ketone body formation instead. The CoA released from ketone body formation goes back to the fatty acid oxidation for production of acetyl-CoA. The ketone bodies are exported to extrahepatic tissues for fuel.
Explain the adverse effects of overproduction of ketone bodies as a result of diabetes or starvation
Overproduction of ketone bodies leads to increasing amounts of free ketone bodies, the capacity of ketone oxidation is overloaded. This leads to lower blood pH, and acidosis, which may lead to coma and death if untreated. Ketosis is a result of elevated ketone concentrations in the blood, and ketoacidosis when combined with acidosis.
