Transcript Metabolism: the Degradation and Synthesis of Living Cells

Instructors for Biochemistry II
• Dr. Yongmei Qin (秦咏梅，Associate
Professor, director of Biochemistry II)
– Tel.:6275-8885 (office); Room 214, New Life
Science Building;
– E-mail: [email protected]
• Dr. Zengyi Chang (昌增益, Professor）
– Tel: 6275-8822 (office); Room 204, New Life
Science Building;
– E-mail: [email protected]
Teaching Assistants for
Biochemistry II
• Ruiyu Kang (康瑞玉)：6275-8056
[email protected]
• Fangyuan Chen (陈方圆):
[email protected]
• Anastasia Ngozi(阿娜莎)：62758056
[email protected]
Did you ever ask these questions?
• How the nutrients that we are ingesting daily
become part of our body and allow growth to
occur (what is the fate of the sugar, fat,
protein and nucleic acids that enter our body
along with the food ?)
• Why do we become fat by only eating sugar?
• What is the molecular nature of the large
number of genetic diseases? How can we
find ways to prevent and treat them?
• What does O2 do for us? And how is O2
produced by plants?
• How do the various living organisms
“produce” and “consume” energy? …
Biochemistry II
Metabolism: The
totality of the
transformation of
biomolecules (matter)
and energy
Definition of Metabolism
• The entire highly integrated and
regulated network of chemical
transformations (as stepwise
metabolic pathways catalyzed by
many enzymes) occurring in a living
organism (through which cells
extract energy and reducing power
from its environment, as well as
synthesize the building blocks of its
macromolecules and then the
macromolecules themselves).
Coenzymes (vitamines)
Amino acids
carbohydrate
hormones
nucleotides
Amino acids
lipids
22nd edition designed by Dr. Donald E. Nicholson
For maps of metabolic pathways
see: http://www.iubmbnicholson.org/
metabolism is categorized into
two types
• Catabolism (biodegradation): larger
molecules (nutrients and cell
constituents) are broken down (often
via exergonic reactions) to salvage
(reuse) their components or/and to
generate energy.
• Anabolism (biosynthesis): The
generation of biomolecules from
simpler
components
via
The Ying
& Yang (often
of Metabolism
(Fuels)
The Ying & Yang of Metabolism
Exergonic Oxidation
Biodegradation
Output of energy
Simpler
Metabolites
Complex
Metabolites
Input of energy
Endergonic Reduction
Biosynthesis
Major Roles of Metabolism
• Extract energy and reducing power from
the environment (photosynthesis and
oxidative degradation of nutrients).
• Generation (interconversion) of all the
biomolecules for a living organism.
Thus comes the term
“Dynamic Biochemistry”
(Fuels)
The role of Metabolism
Extract energy and reducing power
ATP: Energy currency
Also for mobility,
transport of nutrients
and so on.
Generate all biomolecules
Classification of organisms
based on trophic (“feed”)
strategies
• Autotrophs—synthesize all cellular
components from simple inorganic
molecules (e.g, H2O, CO2, NH3, H2S).
• Heterotrophs—Derive energy from
oxidation of organic compounds (made
by autotrophs).
Metabolism in various living
organisms allow carbon, oxygen
and nitrogen to be cycled in the
biosphere.
The cycling of matter is driven
by the flow of energy in one
direction through the biosphere!
Metabolism allows the cycling of C/O
and the flow of energy in the biosphere
glucose
Producers
Consumers
H2O
Metabolism also
allows the cycling
of N in the biosphere
(NH4+)
NO3NO2-
General Features of Metabolism
• Occurs in specific cellular (tissue and organ) locations
as a series of enzyme-catalyzed linear, branched or
circular reactions, or pathways.
• Highly coupled and interconnected (“Every road leads
to Rome”).
• Highly regulated (often reciprocally) to achieve the
best economy (“Balanced supply and demand”).
• The number of reactions is large (over 1000), however,
the number of types of reactions is relatively small
(what happens in animal respiration happens in
plant photosynthesis).
• Well conserved during evolution: reflecting the unity
of the life phenomena (“what happens in bacteria
happens in human being”).
(乙酰辅酶A)
General approaches for studying
metabolism
• Purification and Chemical characterization of
metabolites;
• Tracing the fates of certain biomolecules in living
subjects (via such chemical labels as isotopes).
• Isolation of genetic mutants having genetic
defects.
• Identification and characterization of enzymes.
Issues for current and future
investigation on metabolism
• Continue to unveil new pathways and new regulation
strategies of metabolism.
• Studies on enzymes.
• Observation of metabolic processes in intact living organisms
(e.g., in the brains under various states)
• Metabolism differences among various organisms or various
states of the same organism (for diagnosing and treating
such diseases as cancer, infections of bacteria or viruses,
obesity, etc; to understand aging).
• Appropriate and inappropriate nutrition.
• Biotechnological application of knowledge learned from
metabolic studies in medicine, agriculture and industry.
•
Nobel Prizes in revealing the
Metabolism of living matter (1)
• 1907, Eduard Buchner: cell-free fermentation.
• 1922, Archibald B. Hill: production of heat in the muscle?;
Otto Meyerhof: fixed relationship between the consumption
of oxygen and the metabolism of lactic acid in the muscle.
• 1923, Frederick Grant Banting, John James Richard
Macleod: discovery of insulin.
• 1929, Arthur Harden, Hand von Euler-Chelpin: fermentation
of sugar and fermentative enzymes.
• 1929, Christiaan Eijkman: antineuritic vitamin; Sir
Frederick Gowland Hopkins: growth-stimulating vitamins.
• 1931, Otto Heinrich Warburg: nature and mode of action of
the respiratory enzyme.
Nobel Prizes in revealing the
Metabolism of living matter (2)
• 1934, George Hoyt Whipple, George Richards Minot,
William Parry Murphy: liver therapy in cases of anaemia.
• 1937, Albert Szent-Gyorgyi: biological combustion, vitamin
C and the catalysis of fumaric acid.
• 1943, Henrik Carl Peter Dam: discovery of vitamin K;
Edward Adelbert Doisy: chemical nature of vitamin K.
• 1947, Carl Cori and Gerty Cori: catalytic conversion of
glycogen; Bernardo Houssay: hormone of the anterior
pituitary lobe in the metabolism of sugar.
• 1950, Edward Calvin Kendall, Tadeus Reichstein,Philip
Showalter Hench: hormones of the adrenal cortex, their
structure and biological effects.
• 1953, Hans Krebs: citric acid cycle; Fritz Lipmann: role of
co-enzyme A in metabolism.
• 1955, Axel Hugo Theodor Theorell: nature and mode of
action of oxidation enzymes“.
Nobel Prizes in revealing the
Metabolism of living matter (3)
• 1961, Melvin Calvin: carbon dioxide assimilation in
plants.
• 1964, Konrad Bloch, Feodor Lynen: cholesterol and fatty
acid metabolism.
• 1971, Earl W. Sutherland, Jr.: mechanisms of the action
of hormones.
• 1978, Peter Mitchell: chemiosmotic theory of biological
energy transfer.
• 1982, Sune K. Bergström, Bengt I. Samuelsson, John R.
Vane: prostaglandins and related biologically active
substances.
• 1985. Michael S. Brown, Joseph L. Goldstein: regulation
of cholesterol metabolism.
Nobel Prizes in revealing the
Metabolism of living matter (4)
• 1988, Sir James W. Black, Gertrude B. Elion, George
H. Hitchings: principles for drug treatment.
• 1988, Johann Deisenhofer, Robert Huber, Hartmut
Michel: photosynthetic reaction centre.
• 1992, Edmond H. FischerEdwin G. Krebs: reversible
protein phosphorylation as a biological regulatory
mechanism.
• 1994, Alfred G. GilmanMartin Rodbell: G-proteins
and the role of these proteins in signal transduction
in cells.
• 1997, Paul D. Boyer, John E .Walker: synthesis of
ATP.
• 1998, Robert F. Furchgott, Louis J. Ignarro, Ferid
Murad: nitric oxide as a signalling molecule in the
cardiovascular system.
Nobel Prizes in revealing the
Metabolism of living matter (5)
• 1999, Gunter Blobel: protein localization.
• 2000, Arvid Carlsson, Paul Greengard, Eric R. Kandel:
signal transduction in the nervous system.
• 2001, Leland H. Hartwell, Tim Hunt, Sir Paul Nurse:
regulators of the cell cycle.
• 2002, Sydney Brenner, H. Robert Horvitz, John E.
Sulston: regulation of organ development and
programmed cell death.
• 2004, Aaron Ciechanover, Avram Hershko, Irwin
Rose: ubiquitin-mediated protein degradation.
Major aspects that will be
covered in Biochemistry II
• General principles for bioenergetics.
• Oxidative degradation of fuels (glycolysis, boxidation, a-ketoacid oxidation, citric acid cycle),
generating NADH, FADH2, ATP, and CO2.
• Oxidation of NADH and FADH2 by O2 and generation
of ATP and H2O (respiratory chains, ATP synthase).
• Biosynthesis of carbohydrates (including photosynthsis),
fatty acids, amino acids, and nucleotides.
• Metabolites, chemical reactions, enzymes, regulations,
with wide applications in medicine, agriculture, and
biotechnology.
How to study metabolism
• Compare and relate (interconnect) the chemical
reactions (Where are you in the metabolism network?)
• Try to contemplate on the ways the living organisms
used to achieve a balanced and dynamic steady state
(How could the multilayered regulation cooperate so
effectively?).
• Understand the classical experiments and thoughts
that led to the revelation of the knowledge described
(Does He/she deserve the Nobel Prize?).
• Be aware of the nature of the data (Could this
observations from in vitro studies be extended to what
happens in vivo?).
• Understand the aspects that need further studies (Do I
still have a chance to win a Nobel Prize?).
Enjoy Biochemistry II: a
course that will allow
you to learn what life is
really all about.
Scoring policies for this course
• Tests (attendance): 10%;
• Critical reading of a research paper (one
paper for each two students): 15%;
• Final Exam: 75%.
Date Chapter
Lecturer
Sept. 12
Over view of metabolism and Chapter 13: Principles of Bioenergetics
Dr. Zengyi Chang
Sept. 19
Chapter 14 Glycolysis & and Pentose phosphate pathway
Dr. Zengyi Chang
Sept. 26
Chapter 16 The Citric Acid Cycle
Dr. Zengyi Chang
Oct. 10
Chapter 17 Fatty Acid Catabolism
Dr. Yongmei Qin
Oct. 17
Chapter 18 Amino Acid Oxidation & Production of Urea
Dr. Yongmei Qin
Oct. 24
Chapter 18 Amino Acid Oxidation & Production of Urea
Dr. Yongmei Qin
Oct. 31
Chapter 19 Oxidative phosphorylation and photophosphorylation
Dr. Zengyi Chang
Nov. 7
Chapter 19 Oxidative phosphorylation and photophosphorylation
Dr. Zengyi Chang
Nov. 14
Chapter 14 GLuconeogenesis
Chapter 15 Principles of Metabolic regulation: Glucose and GLycogen
Dr. Yongmei Qin
Nov. 21
Chapter 20 Carbohydrate Biosynthesis in plants
Dr. Yongmei Qin
Nov. 28
Chapter 21 Lipid biosynthesis
Dr. Yongmei Qin
Dec. 5
Chapter 21 Lipid biosynthesis
Dr. Yongmei Qin
Dec. 12
Chapter 22 Biosynthesis of amino acids, nucleotides and related molecules
Dr. Zengyi Chang
Dec. 19
Dec 26
Chapter 22 Biosynthesis of amino acids, nucleotides and related molecules
Chapter 23 Integration and hormonal regulation of mammalian metabolism
Dr. Zengyi Chang
Dr. Zengyi Chang