Learning goals case 3
1. What happens when you eat? (insulin, glycogenesis, lipogenesis)
Glucose
LIVER
- After absorption in the small intestine, the glucose concentration is 10 mmol/L
- Hepatocytes are exposed to high concentration of glucose, livers cells have GLUT-2 glucose
transporters (independed to insulin). The more glucose in the blood, the more movement
into the hepatocyte.
- In the hepatocyte glucose is phosphorylated into glucose-6-phosphate by glucokinase.
- Glucose 6-phosphate may enter the pathways of glycogen synthesis or glycolysis.
Glycogenesis:
Insulin and glucose both activate the storage of glucose as glycogen. They activate
the main regulatory enzyme of glycogen synthesis (glycogen synthase) and inhibit
glycogen breakdown (by glycogen phosphorylase). glycogen storage occurs
Glycolysis
Glucose6-phosphate can also be metabolized via glycolysis to pyruvate in
hepatocytes. Some of the resulting pyruvate may be oxidized directly in the
tricarboxylic acid cycle, some released after conversion to lactate. ( Most of the
energy required by the liver for its multiple metabolic purposes is, however, derived
from the oxidation of amino acids and fatty acids rather than glucose. )
, Insulin…
- acts via PKB to phosphorylate and inactivate glycogen synthase kinase-3 (GSK-3)
- It also activates phosphatase- 1 G bringing about the dephosphorylating (and activation) of
glycogen synthase (from the b to a variant)
- Insulin also inhibits glycogenolysis as described above (gly phosphorylase from a into b).
Thus, there is coordinated control of glycogen synthesis and breakdown: when one process is
stimulated, the other is inhibited
SKELETAL MUSCLE
- Mediated by the insulin-sensitive glucose transporter GLUT4 , raising insulin levels brings
more transporters to the membrane. Insulin thus increases the rate at which muscle takes up
glucose from the blood.
- Glucose can be used for…
Glycogen synthesis
As in the liver, insulin stimulates the enzyme glycogen synthase in muscle and
inhibits the enzyme glycogen phosphorylase. Thus, when the plasma insulin
concentration is high after a meal, glucose will be stored as glycogen in skeletal
muscle. However, the enzymes are a little different than in the liver
Muscle glycogen synthase has sites that can be phosphorylated by protein
kinase-A, which are lacking in the liver isoform. This would give adrenaline a
particular ability (acting through cAMP and PKA) to switch off glycogen
synthesis in muscle while stimulating glycogen breakdown by the means
described for the liver
muscle glycogen phosphorylase is activated by AMP and inhibited by glucose
6phosphate. These will play a role in stimulating glycogen breakdown when
the energy status of the muscle cell is low (use of ATP for contraction will be
accompanied by some conversion to AMP).
Glycolysis
1. What happens when you eat? (insulin, glycogenesis, lipogenesis)
Glucose
LIVER
- After absorption in the small intestine, the glucose concentration is 10 mmol/L
- Hepatocytes are exposed to high concentration of glucose, livers cells have GLUT-2 glucose
transporters (independed to insulin). The more glucose in the blood, the more movement
into the hepatocyte.
- In the hepatocyte glucose is phosphorylated into glucose-6-phosphate by glucokinase.
- Glucose 6-phosphate may enter the pathways of glycogen synthesis or glycolysis.
Glycogenesis:
Insulin and glucose both activate the storage of glucose as glycogen. They activate
the main regulatory enzyme of glycogen synthesis (glycogen synthase) and inhibit
glycogen breakdown (by glycogen phosphorylase). glycogen storage occurs
Glycolysis
Glucose6-phosphate can also be metabolized via glycolysis to pyruvate in
hepatocytes. Some of the resulting pyruvate may be oxidized directly in the
tricarboxylic acid cycle, some released after conversion to lactate. ( Most of the
energy required by the liver for its multiple metabolic purposes is, however, derived
from the oxidation of amino acids and fatty acids rather than glucose. )
, Insulin…
- acts via PKB to phosphorylate and inactivate glycogen synthase kinase-3 (GSK-3)
- It also activates phosphatase- 1 G bringing about the dephosphorylating (and activation) of
glycogen synthase (from the b to a variant)
- Insulin also inhibits glycogenolysis as described above (gly phosphorylase from a into b).
Thus, there is coordinated control of glycogen synthesis and breakdown: when one process is
stimulated, the other is inhibited
SKELETAL MUSCLE
- Mediated by the insulin-sensitive glucose transporter GLUT4 , raising insulin levels brings
more transporters to the membrane. Insulin thus increases the rate at which muscle takes up
glucose from the blood.
- Glucose can be used for…
Glycogen synthesis
As in the liver, insulin stimulates the enzyme glycogen synthase in muscle and
inhibits the enzyme glycogen phosphorylase. Thus, when the plasma insulin
concentration is high after a meal, glucose will be stored as glycogen in skeletal
muscle. However, the enzymes are a little different than in the liver
Muscle glycogen synthase has sites that can be phosphorylated by protein
kinase-A, which are lacking in the liver isoform. This would give adrenaline a
particular ability (acting through cAMP and PKA) to switch off glycogen
synthesis in muscle while stimulating glycogen breakdown by the means
described for the liver
muscle glycogen phosphorylase is activated by AMP and inhibited by glucose
6phosphate. These will play a role in stimulating glycogen breakdown when
the energy status of the muscle cell is low (use of ATP for contraction will be
accompanied by some conversion to AMP).
Glycolysis
