Lectures BGZ2024 Food for Life
lecture: Integration of carbohydrate and fat metabolism
Key players in regulation of energy metabolism
- Sympathetic nervous system: substrate mobilization
- Endocrine system: substrate storage, substrate mobilization
Glucagon production is done by the pancreatic alfa- cells and insulin production is done by
pancreatic beta-cells. If the glucose concentration is high, insulin will be produced and if the
glucose concentration is low, glucagon will be produced. glucagon and insulin are the two
main hormones
Role of the liver in glucose metabolism
We eat food nutrients enter the circulation elevation of blood glucose concentration
central nervous system needs this glucose the glucose is taken up by skeletal muscle also a
big part of the glucose is stored in the liver
When there is no entry of nutrients from the gut into the circulation (example during the night).
The liver is the only organ that can supply glucose to the circulation.
Glycogenesis: process of glycogen being stored/ formation of glycogen:
Process that takes place in the hepatocyte: glucose enters hepatocyte via GLUT2, glucose is now
intracellularly available glucose is converted to glucose-6-phosphate by enzyme glucokinase.
Glucose-6-phosphate can now either enter the glycolysis and the krebcycle (TCA) or a different
pathway: the pentose phosphate pathway when there is more energy than needed, there is
conversion of glucose-6-phosphate into glucose-1-phosphate by phosphoglucomutase
glucose-1-phosphate is converted into UDP- glucose by UDP glucose pyro phosphorylase UPD-
glucose is converted into glycogen by glycogen synthase
- Costs energy/ ATP to store glucose in the form of glycogen
- Why convert glucose into glycogen? To prevent that a lot of fluid will enter the liver. if
you have multiple separate glucose molecules, the water will move to the place from
where there are less particles to where there are more particles and you don’t want the
liver to swell up. It keeps the osmolarity lower so there is no excessive uptake of fluid
- 70-100g of liver glycogen
Glycogenolysis: process of breakdown of glycogen:
After a meal insulin levels raise, because the blood glucose goes up. Insulin stimulates the
enzyme glycogen synthase, so it stimulates the conversion to glycogen. When the glucose is
needed again, example during the night of during exercise, glycogen can be degraded/ broken
down to glucose-1-phosphate by glycogen phosphorylase. When glycogen is broken down to
glucose-1-phosphate, the opposite process goes on. Glucose-1-phosphate becomes glucose-6-
phosphate and this becomes glucose by glucose-6-phosphatase (this enzyme is present in liver
cells but not in muscle cells, this is why skeletal muscle cannot release glucose into the
circulation). After all this the glucose is released into the circulation.
, - Insulin and glucose inhibit glycogen phosphorylase, because after a meal, you get an
increase in insulin and glucose. You don’t want more glucose, but you want to convert
that to glycogen.
- Glucagon stimulates it, because during the night, we need glucose and this will be
released into the circulation of glycogen phosphorylase will be stimulated.
- Adrenaline stimulates it, because adrenaline is being released during exercise or in
stress situation, and then we need the additional glucose in our muscles
Side note: Glucose can enter the liver without insulin: is insulin- independent
Role of the muscles in glucose metabolism
Insulin plays a big role in the uptake of glucose in skeletal muscle.
Glycogenesis:
Process that takes place in the myocyte: glucose enters myocyte via GLUT4 and is now
intracellularly available glucose converted to glucose-6-phosphate by hexokinase. Glucose-6-
phosphate can now either enter the glycolysis and the krebcycle (TCA) or it is converted to
glucose-1-phosphate by phosphoglucomutase this is converted to UDP-glucose by UDP
glucose pyro phosphorylase UDP- glucose is converted into glycogen by glycogen synthase (all
same as in the liver)
- 350-800g glycogen stored in muscles
- A lot of carbohydrates+ a lot of exercise = a huge glycogen storage (needed for topsport)
After a meal insulin raises insulin now doesn’t only stimulate glycogen synthase, but also
the translocation of the GLUT4, because this transporter is stored is vesicles (intracellular) and
only when insulin binds to its receptor, there is translocational GLUT4 towards the cell
membrane. This is also activated by calcium, because this is needed for muscle contraction, so
you need more glucose. Insulin also activates the enzyme hexokinase. Adrenaline inhibits
glycogen synthase, because when you exercise you want glycogen breakdown.
Glycogenolysis:
There is no glucose-6-phosphatase in the myocyte, so glucose-6-phosphate cannot be converted
back into glucose no release of glucose via muscles into circulation.
- But why glycogen breakdown in the muscles? Because the glucose-6-phosphate can go
into the glycolysis and kreb cycle
Regulation of glycogen phosphorylase: insulin and glucose inhibit this enzyme (also in liver).
also glucose-6-phosphate inhibits glycogen phosphorylase, because if there are already high
levels of glucose-6-phosphate, you don’t want any breakdown of glucose. Adrenaline, calcium
and AMP are stimulators of glycogen phosphorylase. If AMP levels are high, de energy status of a
cell is low, so we need more energy. Glycogen needs to be broken down and glucose is produced.
AMP, calcium and adrenaline are high during exercise, you need glycogen breakdown and you
need glucose.
Side note: glucose uptake by the muscle is insulin dependent, insulin activates hexokinase and
glycogen synthase.
- There can also be independent glucose uptake in active muscle via AMPK pathway.
lecture: Integration of carbohydrate and fat metabolism
Key players in regulation of energy metabolism
- Sympathetic nervous system: substrate mobilization
- Endocrine system: substrate storage, substrate mobilization
Glucagon production is done by the pancreatic alfa- cells and insulin production is done by
pancreatic beta-cells. If the glucose concentration is high, insulin will be produced and if the
glucose concentration is low, glucagon will be produced. glucagon and insulin are the two
main hormones
Role of the liver in glucose metabolism
We eat food nutrients enter the circulation elevation of blood glucose concentration
central nervous system needs this glucose the glucose is taken up by skeletal muscle also a
big part of the glucose is stored in the liver
When there is no entry of nutrients from the gut into the circulation (example during the night).
The liver is the only organ that can supply glucose to the circulation.
Glycogenesis: process of glycogen being stored/ formation of glycogen:
Process that takes place in the hepatocyte: glucose enters hepatocyte via GLUT2, glucose is now
intracellularly available glucose is converted to glucose-6-phosphate by enzyme glucokinase.
Glucose-6-phosphate can now either enter the glycolysis and the krebcycle (TCA) or a different
pathway: the pentose phosphate pathway when there is more energy than needed, there is
conversion of glucose-6-phosphate into glucose-1-phosphate by phosphoglucomutase
glucose-1-phosphate is converted into UDP- glucose by UDP glucose pyro phosphorylase UPD-
glucose is converted into glycogen by glycogen synthase
- Costs energy/ ATP to store glucose in the form of glycogen
- Why convert glucose into glycogen? To prevent that a lot of fluid will enter the liver. if
you have multiple separate glucose molecules, the water will move to the place from
where there are less particles to where there are more particles and you don’t want the
liver to swell up. It keeps the osmolarity lower so there is no excessive uptake of fluid
- 70-100g of liver glycogen
Glycogenolysis: process of breakdown of glycogen:
After a meal insulin levels raise, because the blood glucose goes up. Insulin stimulates the
enzyme glycogen synthase, so it stimulates the conversion to glycogen. When the glucose is
needed again, example during the night of during exercise, glycogen can be degraded/ broken
down to glucose-1-phosphate by glycogen phosphorylase. When glycogen is broken down to
glucose-1-phosphate, the opposite process goes on. Glucose-1-phosphate becomes glucose-6-
phosphate and this becomes glucose by glucose-6-phosphatase (this enzyme is present in liver
cells but not in muscle cells, this is why skeletal muscle cannot release glucose into the
circulation). After all this the glucose is released into the circulation.
, - Insulin and glucose inhibit glycogen phosphorylase, because after a meal, you get an
increase in insulin and glucose. You don’t want more glucose, but you want to convert
that to glycogen.
- Glucagon stimulates it, because during the night, we need glucose and this will be
released into the circulation of glycogen phosphorylase will be stimulated.
- Adrenaline stimulates it, because adrenaline is being released during exercise or in
stress situation, and then we need the additional glucose in our muscles
Side note: Glucose can enter the liver without insulin: is insulin- independent
Role of the muscles in glucose metabolism
Insulin plays a big role in the uptake of glucose in skeletal muscle.
Glycogenesis:
Process that takes place in the myocyte: glucose enters myocyte via GLUT4 and is now
intracellularly available glucose converted to glucose-6-phosphate by hexokinase. Glucose-6-
phosphate can now either enter the glycolysis and the krebcycle (TCA) or it is converted to
glucose-1-phosphate by phosphoglucomutase this is converted to UDP-glucose by UDP
glucose pyro phosphorylase UDP- glucose is converted into glycogen by glycogen synthase (all
same as in the liver)
- 350-800g glycogen stored in muscles
- A lot of carbohydrates+ a lot of exercise = a huge glycogen storage (needed for topsport)
After a meal insulin raises insulin now doesn’t only stimulate glycogen synthase, but also
the translocation of the GLUT4, because this transporter is stored is vesicles (intracellular) and
only when insulin binds to its receptor, there is translocational GLUT4 towards the cell
membrane. This is also activated by calcium, because this is needed for muscle contraction, so
you need more glucose. Insulin also activates the enzyme hexokinase. Adrenaline inhibits
glycogen synthase, because when you exercise you want glycogen breakdown.
Glycogenolysis:
There is no glucose-6-phosphatase in the myocyte, so glucose-6-phosphate cannot be converted
back into glucose no release of glucose via muscles into circulation.
- But why glycogen breakdown in the muscles? Because the glucose-6-phosphate can go
into the glycolysis and kreb cycle
Regulation of glycogen phosphorylase: insulin and glucose inhibit this enzyme (also in liver).
also glucose-6-phosphate inhibits glycogen phosphorylase, because if there are already high
levels of glucose-6-phosphate, you don’t want any breakdown of glucose. Adrenaline, calcium
and AMP are stimulators of glycogen phosphorylase. If AMP levels are high, de energy status of a
cell is low, so we need more energy. Glycogen needs to be broken down and glucose is produced.
AMP, calcium and adrenaline are high during exercise, you need glycogen breakdown and you
need glucose.
Side note: glucose uptake by the muscle is insulin dependent, insulin activates hexokinase and
glycogen synthase.
- There can also be independent glucose uptake in active muscle via AMPK pathway.
