Glycogen Metabolism Flashcards
Biochemistry Glycogen Metabolism – Dr Stephen C Land
What is glycogenesis?
synthesis of glycogen from glucose
What is glycogenolysis?
breakdown of glycogen to form glucose
What is gluconeogenesis?
de novo synthesis of glucose from metabolic precursors (lactate, amino acids, glycerol)
What is glycogen?
Main storage form of glucose in liver and muscle cells
What is the use of liver glycogen?
broken down between meals and released to maintain blood glucose levels for red blood cells and brain
What is the use of muscle glycogen?
it is not able to be used for the maintenance of blood glucose levels
it provides energy via glycolysis and the TCA (kreb’s cycle) during bursts of physical activity
When is gluconeogenesis the main source of blood glucose?
overnight when the hepatic glycogen is depleted
What is the structure of glycogen?
it is a polymer of glucose molecules
the molecules are joined by alpha 1-4 glycosidic links
the branches are joined to the chain by alpha 1-6 glycosidic links
How are glucose molecules added to the glycogen chain?
glucose residues can only be added to an existing chain
there needs to be a glycogen primer with at least 4 glucose residues
the primer is covalently attached to a protein called glycogenin
What enzyme converts glucose to glucose-6-phosphate?
hexokinase
What enzyme converts glucose-6-phosphate to glucose-1-phosphate?
phosphoglucomutase
What enzyme converts glucose-1-phosphate to UDP-glucose?
UDP-glucose pyrophosphorylase
What enzyme converts UDP-glucose to [glucose]n+1 + UDP?
glycogen synthase
What molecule within the glycogen synthesis process can enter into glycolysis?
glucose-6-phosphate
What is considered to be an active form of glucose?
UDP-glucose
What is released upon the hydrolysis of the phosphate ester linkage in a nucleotide sugar?
energy
How is glycogen synthesised from UDP-glucose?
One glucose molecule is added to glycogen at a time
Can only extend the chains of glycogen, it can not start new molecules
Can not introduce branches
Rate limiting enzyme of glycogenesis
What enzyme introduces branching to the glycogen?
transglycosylase, introduces alpha 1-6 glycosidic branches into glycogen
approximately every 10 glucose residues
What enzyme catalyses the formation of glucose-1-phosphate in glycogenolysis?
glycogen phosphorylase
what are [glucose]n + phosphate (Pi)
converted to in glycogenolysis?
glucose-1-phosphate + [glucose]n-1
How many glucose molecules can be cleaved from a glycogen molecule at once?
1 glucose molecule is cleaved off the ends of glycogen at a time
What is the second step in glycogenolysis?
glucose-1-phosphate is converted to glucose-6-phosphate
What happens to the glucose-6-phosphate molecule produced by glycogenolysis in the liver?
glucose 6-phosphate can be de-phosphorylated and the resulting glucose released into the blood stream
What happens to the glucose-6-phosphate molecule produced by glycogenolysis in the skeletal muscle?
it is used to provide energy via glycolsis and the TCA (krebs) cycle as t can’t be phosphorylated
what conditions require the process of gluconeogenesis?
prolonged starvation
What are the precursors which are used to synthesise new glucose through glucneogenesis?
Lactate - skeletal muscle synthesizes in anaerobic conditions
Amino acids - derived from muscle protein through proteolysis
Glycerol - derived from triglycerides by lipolysis in adipose tissue
How is the energy for the gluconeogenesis ontained?
through the oxidation of fatty acids released from adipose tissue
Where does gluconeognesis take place?
mainly in the liver but a small bit in the kidneys
Is gluconeogenesis essentially the reverse of glycolysis?
NO gluconeogenesis is NOT the reverse of glycolysis
What 3 essentially irreversible enzyme reactions are there in glycolysis?
hexokinase
phosphofructokinase
pyruvate kinase
How does glucogenesis bypass the irreversible reactions of glcolysis?
- uses 4 unique liver enzymes
- synthesises oxaloacetate in mitochondria the TCA cycle intermediate (oxaloacetate is important for accepting acetyl groups from fat breakdown)
- is an energy consuming process
Gluconeogenesis
2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 4 H+ + 6 H2O
glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ + 2 H+
What is the Cori cycle?
The cycle of lactate prodution in muscle cells through anaerobic respiration and the synthesis of glucose from lactate in the liver. This glucose is then carried in the bloodstream back to the skeletal muscle for further anaeorbic respiration
How are amino acids used as a precursor for gluconeogenesis?
Different amino acids enter the TCA cycle at different positions but ultimately lead to the synthesis of oxaloacetate and glucose
What are the 2 hormones which regulate glycogenolysis and gluconeogenesis?
Glucagon
Insulin
What does high AMP or ADP indicate?
That the cell is low in energy
What does high ATP indicate?
That the cell is high in energy
What does fructose 2,6-bisphosphate levels show?
high levels - in fed state
low levels - in starved state
What do high levels of citrate, alanine and acetyl-CoA indicate?
that the intermediates or building blocks abundant
How does insulin affect the enzymes involved in glucogen synthesis and lysis?
it inhibits glycogen phosphorylase decreasing the conversion of glycogen to glucose-1-phosphate
it promotes glycogen synthase increasing the conversion of UDP-glucose to glycogen
How does glucagon affect the enzymes involved in glucogen synthesis and lysis?
it inhibits glycogen synthase decreasing the conversion of UDP-glucose to glycogen
it promotes glycogen phosphorylase increasing the conversion of glycogen to glucose-1-phosphate
What hormones increase the activity f glycogen phosphorylase?
glucagon
adrenaline
cortisol
