BGZ2004
Problem 4
Digestion – Absorption – Transport – Utilisation (into ATP) / Storage (into tissues)
This is tightly coordinated by nervous and endocrine system.
Regulation of substrate utilization:
- Substrate supply
- Allosteric modification of enzymes (conformational changes due to binding
of effector to binding site of enzyme; cofactor)
- Covalent modification of enzymes; phosphorylation (under hormonal
control)
- Changes in levels of enzymes (longer term adaptation)
1. What is glyconeogenesis, glycogenese & glycogenolysis?
Glycogenesis: glucose molecules that are combined to form glycogen. It begins
as glucose entering cells is phosphorylated to glucose-6-phosphate and then
converted to its isomer glucose-1-phosphate. The terminal phosphate group is
cleaved off as the enzyme glycogen synthase catalyzes the attachment of
glucose to the growing chain.
Glycogenolysis: the breakdown of glycogen into glucose; splitting of glycogen.
The enzyme glycogen phosphorylase oversees phosphorylation and cleavage of
glycogen to release glucose-1-phosphate, which is then converted to glucose-6-
phosphate. This can enter the glycoltyic pathway for energy. Only hepatocytes
(cells in liver), contain the enzyme glucose-6-phosphatease, which removes the
terminal phosphate; producing free glucose. Glucose can diffuse into the blood.
Glycolysis; breakdown of glucose into pyruvate, which can then enter
the citric acid cycle or into lactate.
- In fed conditions
Gluconeogenesis: the built up of glucose from glycerol / lactate / alanine
(an amino acid), in the liver
- In starving conditions. When dietary sources and glucose reserves have
been used up and blood glucose levels are beginning to drop. It protect the
body from hypoglycermia, so that ATP synthesis can continue.
, 2. What is the functions of the following organs in regulation of
the blood glucose (and how are they stored -> Liver, muscles
and adipose tissue)? (Hormones!)
a. Pancreas
The pancreas
The pancreas is both:
- Exocrine: to secrete enzymes into the GI tract
, - Endocrine: it secretes hormones
The pancreas contains the Islets of Langerhans, which are endocrine cells. There
are three types of endocrine cells:
o Alpha cells: they secrete glucagon in the head of the pancreas
o When glucose concentration is low
o Beta cells: they secrete insulin in the tail of the pancreas
o When glucose concentration is high
o D cells: secrete somatostatin
Insulin is a peptide hormone, the most important function is to regulate glucose
in the plasma. As glucose concentration in the blood rises, glucose can flow into
cells and is phosphorylated.
After absorption of nutrients from a meal, plasma glucose rises. The increase in
blood glucose inhibits glucagon secretion and stimulates insulin release. Insulin
promotes glucose transfer into cells.
Secretion of insulin:
- Stimulated by increased plasma glucose: When plasma glucose rises
above 100 mg/dL. Glucose reaches pancreatic beta cells, where it is taken
up by GLUT2 transporters. With more glucose available as substrate, ATP
production increases and ATP-gated K+ channels close. The cell
depolarizes, voltage-gated Ca2+ channels open and Ca2+ entry initiates
exocytosis of insulin.
- Stimulated by increased amino acids in plasma
- Feedforward effects of GI hormones
- Parasympathetic activity
- Sympathetic activity inhibits insulin secretion
Liver
When food enters the body, glucose concentration rises. Glucose can be
converted into muscles, into the brain or else it gets stored in the liver. When
fasting, the liver is the only tissue that can provide glucose for energy.
The liver cells are called hepatocytes. Glucose is absorbed from the intestine to
the portal vein, where its concentration can become 10 mmol/l after a meal. The
hepatocytes are then exposed to high concentrations of glucose during the
absorptive phase. The GLUT-2 transporter on liver cells is responsive for insulin,
when glucose concentrations outside the cells are high, glucose is transported
into the cell. Figure 5.2 page 96 Freith. GLUT2 is independent.
Glycogenesis
Problem 4
Digestion – Absorption – Transport – Utilisation (into ATP) / Storage (into tissues)
This is tightly coordinated by nervous and endocrine system.
Regulation of substrate utilization:
- Substrate supply
- Allosteric modification of enzymes (conformational changes due to binding
of effector to binding site of enzyme; cofactor)
- Covalent modification of enzymes; phosphorylation (under hormonal
control)
- Changes in levels of enzymes (longer term adaptation)
1. What is glyconeogenesis, glycogenese & glycogenolysis?
Glycogenesis: glucose molecules that are combined to form glycogen. It begins
as glucose entering cells is phosphorylated to glucose-6-phosphate and then
converted to its isomer glucose-1-phosphate. The terminal phosphate group is
cleaved off as the enzyme glycogen synthase catalyzes the attachment of
glucose to the growing chain.
Glycogenolysis: the breakdown of glycogen into glucose; splitting of glycogen.
The enzyme glycogen phosphorylase oversees phosphorylation and cleavage of
glycogen to release glucose-1-phosphate, which is then converted to glucose-6-
phosphate. This can enter the glycoltyic pathway for energy. Only hepatocytes
(cells in liver), contain the enzyme glucose-6-phosphatease, which removes the
terminal phosphate; producing free glucose. Glucose can diffuse into the blood.
Glycolysis; breakdown of glucose into pyruvate, which can then enter
the citric acid cycle or into lactate.
- In fed conditions
Gluconeogenesis: the built up of glucose from glycerol / lactate / alanine
(an amino acid), in the liver
- In starving conditions. When dietary sources and glucose reserves have
been used up and blood glucose levels are beginning to drop. It protect the
body from hypoglycermia, so that ATP synthesis can continue.
, 2. What is the functions of the following organs in regulation of
the blood glucose (and how are they stored -> Liver, muscles
and adipose tissue)? (Hormones!)
a. Pancreas
The pancreas
The pancreas is both:
- Exocrine: to secrete enzymes into the GI tract
, - Endocrine: it secretes hormones
The pancreas contains the Islets of Langerhans, which are endocrine cells. There
are three types of endocrine cells:
o Alpha cells: they secrete glucagon in the head of the pancreas
o When glucose concentration is low
o Beta cells: they secrete insulin in the tail of the pancreas
o When glucose concentration is high
o D cells: secrete somatostatin
Insulin is a peptide hormone, the most important function is to regulate glucose
in the plasma. As glucose concentration in the blood rises, glucose can flow into
cells and is phosphorylated.
After absorption of nutrients from a meal, plasma glucose rises. The increase in
blood glucose inhibits glucagon secretion and stimulates insulin release. Insulin
promotes glucose transfer into cells.
Secretion of insulin:
- Stimulated by increased plasma glucose: When plasma glucose rises
above 100 mg/dL. Glucose reaches pancreatic beta cells, where it is taken
up by GLUT2 transporters. With more glucose available as substrate, ATP
production increases and ATP-gated K+ channels close. The cell
depolarizes, voltage-gated Ca2+ channels open and Ca2+ entry initiates
exocytosis of insulin.
- Stimulated by increased amino acids in plasma
- Feedforward effects of GI hormones
- Parasympathetic activity
- Sympathetic activity inhibits insulin secretion
Liver
When food enters the body, glucose concentration rises. Glucose can be
converted into muscles, into the brain or else it gets stored in the liver. When
fasting, the liver is the only tissue that can provide glucose for energy.
The liver cells are called hepatocytes. Glucose is absorbed from the intestine to
the portal vein, where its concentration can become 10 mmol/l after a meal. The
hepatocytes are then exposed to high concentrations of glucose during the
absorptive phase. The GLUT-2 transporter on liver cells is responsive for insulin,
when glucose concentrations outside the cells are high, glucose is transported
into the cell. Figure 5.2 page 96 Freith. GLUT2 is independent.
Glycogenesis
