4 - Glycogen Metabolism and GLuconeogenesis Flashcards
Where is glycogen found?
Liver and skeletal muscle
What is involved in the mobilization of glycogen?
Sequential phosphorylation of alpha 1,4 glycosidic linkages
GLycogen phosphorylase catalyses the reaction with pyridoxal phosphate releasing glucose-1-P fro the non-reducing end
Glycogen phosphorylase stops at a point four residues away from a branch point. Branch points are for less water for solvation and compaction (more reducing ends = quicker mobilization).
Debranching enzyme needed for alpha 1,6 branch points
How does glucose from glycogen become usable in glycolysis?
GLucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase
Glucose-6-phosphatase can also generate glucose from G-6-P for transport in the blood
What does debranching enzyme do to glycogen?
- alpha1,4-alpha1,4-glucatransferase (transfers triglucose from the branchpoint chain to another outer branch)
- alpha1,6-glucosidase (releases the remaining glucose)
You get one glucose (not G-1-P) from every branchpoint and three G-1-P from regular glycogen phosphorylase activity on the triglucose released
What type of glucose is glycogen synthesized from? Give steps of synthesis
UDP-glucose
- UDP-glucose synthesized from glucose-1-phosphate by UDP-glucose pyrophosphorylase
- Glycogenin acts as primer. A short chain (up to 8) of glucose residues begins synthesis.
- Glycogenin-glucose chain is elongated with additional UDP glucose units by glycogen synthase
- Branching enzyme transfers groups of 6-7 glucose units from a length of at least 11 units to an interior glucose in alpha1,6 linkage
How is glycogen metabolism regulated?
Ser-14 of glycogen phosphorylase
- Phosphorylated: active (a-form)
- Not phosphorylated: less active (b-form)
Phosphorylation mediated by phosphorylase b kinase, which needs ATP and phosphorylase phosphatase
- Phosphorylase kinase activated by cAMP dependent protein kinase and AMP (which accumulates when ATP expenditures are high)
- Epinephrine stimulates glycogenolysis in muscles
- Glucagon stimulates glycogenolysis to replenish blood glucose in the liver
Describe the hormonal regulation of glycogen mobilization
G protein signalling causes adenylate cyclase to synthesis cAMP from ATP to activate phosphorylase kinase, which then activates phosphorylase b kinase which activates glycogen phosphorylase, which activates glycogen phosphorylase a which promotes glycogen mobilization and glycolysis in muscle or conversion of G-1-P to glucose in the hepatocytes.
Inversely, activation of these phosphorylases causes the phosphorylation of Ser in glycogen synthase, which inhibits it. This is to prevent futile cycling.
What are the three reactions of gluconeogenesis where an energy barrier must be overcome?
PFK-1
- AKA fructobisphosphatase, Pi released (no ATP generation), major site of regulation
Hexokinase
- Glucose-6-phosphatase
- Happens on ER
- Pi is released (no ATP generation)
Pyruvate kinase (need two steps to reverse)
- Pyruvate carboxylase converts pyruvate to oxaloacetate in mitochondrial matrix (rest in cytosol)
- Oxaloacetate converted to phosphoenolpyruvate by PEP carboxykinase in presence of GTP
How many ATP are spent to convert two pyruvate to one glucose in gluconeogenesis?
6
True or false, lipids can become glucose or be broken down to glucose.
FALSE FALSE FALSE
But, metabolites of glycolysis (specifically pyruvate - acetyl-CoA) can become fatty acids
List the effectors on PFK-1 and FBPase-1
PFK-1 (glycolysis)
- ATP inhibits
- ADP activates
- AMP activates
- Citrate inhibits
- F-2,6-BisP activates
FBPase-1 (gluconeogenesis)
- AMP inhits
- F-2,6-BisP inhibits
The level of F-2,6-BisP is determined by the glucose level via glucagon, cAMP and protein phosphorylation
What is the liver’s response to low blood glucose?
- Pancreas secretes glucagon
- Acts on liver to increase cAMP
- cAMP increases phosphatase activity of F-2,6-BisPase
- Decreases level of F-2,6-BisP
- Decreases glycolysis and increases gluconeogenesis by affecting PFK-1 and F-1,6-BPase
