Lecture (9) Integration of Metabolism
Lecture (9) Integration of Metabolism
Lecture (9) Integration of Metabolism
Metabolism
By:
Dr/ Mahmoud G. Eldeib
Lecturer of biochemistry and molecular biology
The co-ordination between three metabolites (carbohydrates, lipids
and proteins) called Integration Of Metabolism.
2. Amino acids:
Amino acids derived from a meal containing protein stimulate the release of both
glucagon and insulin.
The glucagon effectively prevents hypoglycemia that would otherwise occur as a result of
increased insulin secretion that occurs after a protein meal.
3. Epinephrine:
Elevated levels of circulating epinephrine produced by the adrenal medulla, or
norepinephrine produced by sympathetic innervation of the pancreas, or both, stimulate
the release of glucagon.
➢Islet tissue of the pancreas responds to the elevated levels of glucose and
amino acids with an increased secretion of insulin and a decreased release
of glucagon.
➢The elevated insulin to glucagon ratio and the ready availability of
circulating substrates make the absorptive state an anabolic period
characterized by increased synthesis of TAG and glycogen to replenish fuel
stores, and enhanced synthesis of protein.
➢During this absorptive period, virtually all tissues use glucose as a fuel.
LIVER: NUTRIENT DISTRIBUTION CENTER
The liver is uniquely situated to process and distribute dietary nutrients
because the venous drainage of the gut and pancreas passes through
the hepatic portal vein before entry into the general circulation.
Carbohydrate metabolism
1. Increased glucose transport: Glucose transport by GLUT-4 into adipocytes is
sensitive to the insulin concentration in the blood.
2. Increased glycolysis: The increased intracellular availability of glucose results in
an enhanced rate of glycolysis.
In adipose tissue, glycolysis serves a synthetic function by supplying glycerol
phosphate for TAG synthesis
3. Increased activity in the HMP: Adipose tissue can metabolize glucose by means
of the HMP, thereby producing NADPH, which is essential for fat synthesis
B. Fat metabolism
1. Increased synthesis of fatty acids: De novo synthesis of fatty acids
from acetyl CoA.
2. TAG synthesis: After consumption of a lipid-containing meal,
hydrolysis of the TAG of chylomicrons (from the intestine) and VLDL
(from the liver) provides adipose tissue with fatty acids.
Because adipocytes lack glycerol kinase, glycerol 3-phosphate used in
TAG synthesis comes from the metabolism of glucose.
3. Decreased TAG degradation: Elevated insulin favors the
dephosphorylated (inactive) form of hormone-sensitive lipase.
• TAG degradation is thus inhibited in the fed state.
RESTING SKELETAL MUSCLE
Carbohydrate metabolism
1. Increased glucose transport: The transient increase in plasma
glucose and insulin after a carbohydrate-rich meal leads to an increase
in glucose transport into muscle cells by GLUT-4.
• Glucose is phosphorylated to glucose 6- phosphate by hexokinase,
and metabolized to provide the energy needs of the cells.
2. Increased glycogen synthesis: The increased insulin to glucagon ratio
and the availability of glucose 6-phosphate favor glycogen synthesis,
particularly if glycogen stores have been depleted as a result of exercise
Fat metabolism
• fatty acids are of secondary importance as a fuel for muscle during the fed
state, in which glucose is the primary source of energy.
• Fat metabolism
• The brain has no significant stores of TAG, and the fatty acids
circulating in the blood make little contribution to energy production
because fatty acids bound to albumin do not efficiently cross the
blood-brain barrier.
LIVER IN FASTING
• Carbohydrate metabolism:
• The primary role of liver in energy metabolism during fasting is maintenance of blood
glucose through the synthesis and distribution of fuel molecules for use by other organs.
• The increased glucagon to insulin ratio causes a rapid mobilization of liver glycogen stores
(which contain about 80 g of glycogen in the fed state) due to phosphorylation (activation)
of glycogen phosphorylase
• Liver glycogen is nearly exhausted after 10–18 hours of fasting; therefore, hepatic
glycogenolysis is a transient response to early fasting.
Increased gluconeogenesis: The synthesis of glucose and its release into the circulation are
vital hepatic functions during fasting
The carbon skeletons for gluconeogenesis are derived primarily from glucogenic amino acids
and lactate from muscle, and glycerol from adipose.
• Fat metabolism
1. Increased fatty acid oxidation: The oxidation of fatty acids obtained
from TAG hydrolysis in adipose tissue is the major source of energy in
hepatic tissue in the postabsorptive state.
• Fat metabolism
1. Increased degradation of TAG: The activation of hormone sensitive lipase and subsequent
hydrolysis of stored TAG are enhanced by the elevated catechol amines epinephrine and,
particularly, norepinephrine. These compounds, which are released from the sympathetic nerve
endings in adipose tissue.
• Glucagon also activates the lipase
2. Increased release of fatty acids: Fatty acids obtained from hydrolysis of stored TAG are primarily
released into the blood, Bound to albumin, they are transported to a variety of tissues for use as
fuel.
• The glycerol produced from TAG degradation is used as a gluconeogenic precursor by the liver.
RESTING SKELETAL MUSCLE IN FASTING
• Glucose transport into skeletal muscle cells via insulin-sensitive GLUT-4 proteins in the
plasma membrane and subsequent glucose metabolism are depressed because of low
levels o circulating insulin.
• Lipid metabolism
• During the first 2 weeks of fasting, muscle uses fatty acids from adipose tissue and
ketone bodies from the liver as fuels.
• After about 3 weeks of fasting, muscle decreases its use of ketone bodies and oxidizes
fatty acids almost exclusively. This leads to a further increase in the already elevated level
of circulating ketone bodies.
• [Note: The increased use of ketone bodies by the brain as a result of their increased
concentration in the blood is correlated with the decreased use of these compounds by
the muscle.]
• Protein metabolism
• During the first few days of fasting, there is a rapid breakdown of
muscle protein, providing amino acids that are used by the liver for
Gluconeogenesis