Transcript Xu-7-integration

general concepts and
characteristics of metabolic
pathways.
Digestion and absorption of dietary carbohydrates
Pathways of glucose metabolism: glycolysis
Pentose phosphate shunt
Gluconeogenesis
Glycogenolysis, glycogenesis
Galactose and fructose metabolism
Glycogen storage disease
Inborn errors of glucose metabolism
Regulation of glucose metabolism.
III-I
Metabolism
III-II
Carbohydrate metabolism
III-III
Digestion and absorption of dietary fats.
Biosynthesis and degradation of fatty acids,
TCA cycle and biological oxidation
phospolipids and triacylglycerols
Biosynthesis of cholesterol, chemistry and
Protein turnover and amino
metabolism of lipoproteins.
acid metabolism
Hyperlipoproteinemias
Lipid storage disease.
Regulation of the metabolic pathways Ketone bodies: their synthesis, utilization
and conditions leading to ketoacidosis,
III-IV
III-V
III-VI
Lipid metabolism
(a) Interlinks between carbohydrate, lipid and amino acid
metabolic pathways.
(b )Cellular compartment and cooperation
(c) Organ interrelationships in metabolism,
(d) Metabolic adaptation in the fed state, fasting and
prolonged starvation.
(e) Blood glucose regulation, and its impairment in
diabetes mellitus.
(f) Metabolic derangements and adaptations in diabetes
mellitus.
(a) Digestion and absorption of dietary protein
(b) General reactions, transamination, its metabolic
and diagnostic significance
(c) Disposal of amino acid nitrogen and detoxication
of urea
(d) Metabolic fate of amino acid carbon skeleton
(e) Sulphur containing amino acids
(f) In born errors of branched chain and aromatic
amino acids
(g) Important amino acid derivatives.
III-I Metabolism
III-II Carbohydrate metabolism
III-III Lipid metabolism
III-IV
Review and Summarize
TCA cycle and biological oxidation
III-V Protein turnover and amino acid
metabolism
III-VI Regulation of the metabolic pathways
III-VI Regulation of the metabolic pathways
1. Interlinks between carbohydrate, lipid and amino acid
metabolic pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
 Key intermediates connect pathways.
 Energy-rich compounds are converted mutually to a great extent.
 Carbohydrate/fat are priority-ranked in mobilizing.
 Key enzymes in pathways are regulated in similar way.
 Energy charge regulates whole status of metabolism.
The major pathways of fuel metabolism in mammals
Only a few tissues, such as liver, can carry
out all the reactions illustrated above.
metabolic pathways for
glucose-6-phosphate in the liver
amino
acids
amino
acids
Summary of metabolic
fates of pyruvate
Overview of
metabolism
Important reactions of intermediary
metabolism regulated by
phosphorylation of enzyme
Many reactions in metabolism are
controlled by the energy status of
the cell.
High concentrations of ATP inhibit the
relative rates of a typical ATP-generating
(catabolic) pathway and simulate the typical
ATP-utilizing (anabolic) pathways
III-VI Regulation of the metabolic pathways
1. Interlinks between carbohydrate, lipid and amino acid
metabolic pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
 Pathways are located in different places in the cell.
 Molecules are transported between subcellular
parts according to the demand
cytosol
protein
degradation
glycogen
synthesis
glycolysis
endoplasmic
reticulum
TCA
β-oxidation
urea cycle
mitochondria
aerobic oxidation
of carbohydrate
ketone
bodies
amino acids
catabolism
fatty acid
synthesis
pentose
phosphate
pathway
lysosome
protein
degradation
Transfer of the starting materials of
lipid anabolism from the
mitochondrion to the cytosol.
1.PEP carboxykinase in mitochondrion
2.PEP carboxykinase in cytosol
Transfer of the starting materials of
gluconeogenesis from the
mitochondrion to the cytosol.
III-VI Regulation of the metabolic pathways
1. Interlinks between carbohydrate, lipid and amino acid
metabolic pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
 Tissues –specific metabolism
 Metabolism is cooperated between tissues.
Only a few tissues, such as liver, can carry out all
the reactions illustrated in slide 7.
Specialized metabolic functions of mammalian tissues
Low blood glucose will
result in brain dysfunction.
Body’s central
metabolic
clearinghouse
Mitochondria occupy up to 40% of
cytoplasmic space.
atherosclerosis , insufficient O2 supply.
the major fuelmetabolizing organs
Artery & Vein
Body’s central
metabolic
clearinghouse
The portal circulation
The portal vein drains almost all of the blood from the digestive tract
and empties directly into the liver.
This circulation of nutrient-rich blood between the gut and liver is called
the portal circulation. It enables the liver to remove any harmful
substances that may have been digested before the blood enters
the main blood circulation around the body—the systemic
circulation.
There are two cycles
between muscle and liver.
The Cori Cycle
The Glucose-Ala Cycle
Mechanisms of
communication between
four major tissues
III-VI Regulation of the metabolic pathways
1. Interlinks between carbohydrate, lipid and amino acid
metabolic pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
Living things coordinate their activities at every level
of their organization through complex signaling
systems involving chemical messengers known as
hormones.
In higher animals, endocrine glands synthesize and
release hormones, which are carried by the bloodstream
to their target cells. The human endocrine systems
secretes a wide variety of hormones that enable the
body to
maintain homeostasis,
respond to wide variety of external stimuli ,
follow various cyclic and developmental programs
Endocrine signaling
Opposing actions of
insulin and glucogon
plus epinephrine
Insulin causes an
increase in glucose uptake,
mainly in muscle cells and
adipocytes,
stimulates storage of glucose
as glycogen, mainly in liver
cells.
Glucagon acts mainly on
liver cells to stimulate
glycogen degradation.
III-VI Regulation of the metabolic pathways
1. Interlinks between carbohydrate, lipid and amino acid
metabolic pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
Feed/Fast largely effect the energy
metabolism in different organs.
The hormones will respond to the
blood glucose and then regulate by
their own ways.
Intertissues
relationships in the
absorptive state
Insulin-dependent
transport system
Intertissue relationship
during starvation
absorbtive
starvation
starvation
absorbtive
starvation
absorbtive
starvation
absorbtive
Key concept map
for feed/fast cycle
III-VI Regulation of the metabolic pathways
1. Interlinks between Carbohydrate, lipid and amino acid
metabolism pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
Regulation of Blood Glucose
Blood glucose levels are not constant—they rise and fall
depending on the body's needs, regulated by hormones.
This results in glucose levels normally ranging from 70
to 110 mg/dl.
The blood glucose level can rise for three reasons: diet,
breakdown of glycogen, or through hepatic synthesis
of glucose.
Eating produces a rise in blood glucose, the extent of
which depends on a number of factors such as the amount
and the type of carbohydrate eaten, the rate of digestion,
and the rate of absorption.
The liver is a major producer of glucose —it releases
glucose from the breakdown of glycogen and also makes
glucose from intermediates of carbohydrate, protein, and
fat metabolism.
The liver is also a major consumer of glucose and can
buffer glucose levels. It receives glucose-rich blood
directly from the digestive tract via the portal vein. The
liver quickly removes large amounts of glucose from the
circulation so that even after a meal, the blood glucose
levels rarely rise above 110 mg/dl in a non-diabetic.
Glucose
homeostasis
blood
glucose
Aspects of the control of blood glucose levels by
pancreatic secretion of insulin and glucagon
Twenty-four-hour plasma profiles in normal
and non-insulin-dependent diabetes
III-VI Regulation of the metabolic pathways
1. Interlinks between Carbohydrate, lipid and amino acid
metabolism pathways.
2. Cellular compartment and cooperation
3. Organ interrelationships in metabolism,
4. Hormonal control of fuel metabolism
5. Metabolic adaptation in the fed state, fasting and prolonged
starvation.
6. Blood glucose regulation, and its impairment in diabetes
mellitus.
7. Metabolic derangements and adaptations in diabetes mellitus.
When the amount of glucose in the blood increases, e.g.,
after a meal, it triggers the release of the hormone
insulin from the pancreas. Insulin stimulates
muscle and fat cells to remove glucose from the blood
cells to breakdown glucose, releasing its energy in the form of ATP
the liver and muscle to store glucose as glycogen
adipose tissue to store glucose as fat
cells to use glucose in protein synthesis
causing the blood sugar level to
decrease to normal levels
Diabetes mellitus is characterized by abnormally
high levels of sugar (glucose) in the blood.
In people with diabetes, blood sugar levels remain high. This
may be because insulin is
not being produced at all,
not made at sufficient levels,
not as effective as it should be.
The most common forms of diabetes are type 1 diabetes (5%),
which is an autoimmune disorder, and type 2 diabetes (95%),
which is associated with obesity.
Gestational diabetes is a form of diabetes that occurs in
pregnancy, and other forms of diabetes are very rare and are
caused by a single gene mutation.
Insulin resistant
Metabolic changes in diabetic ketoacidosis.
How will you review Part III?
List all the Q & A.
Ponder all the Q.
Read all the sentences with underline.
Come from different parts
Part I (a,b,c)
8 points
Part I (d) & II 17 points
Part III
38 points
Part IV-VII
37 points
Biochemistry Examination
70%
Single best answer (from multiple choice questions) (1X10)
Fill in the blanks (1X40)
True/False (1X20)
Essay questions (5X6)
100X 70%
Midterm Test （or assignment） 30 %