Biochemistry II
--Metabolism: The
degradation
and synthesis of biomolecules.
by
Professor Zengyi Chang (昌增益教授）
Tel: 6277-2251
E-mail: changzy@mail.tsinghua.edu.cn
1. An Overview of Metabolism
1.1 The Definition of Metabolism
• The highly integrated network of chemical
transformations.
• Degradation (decreasing order, thus energy
releasing) to provide energy, catabolism;
• Synthesis (increasing order, thus energy
consuming) to provide building materials,
anabolism.
The energy supply
and demand in
Heterotrophs:
the ATP-ADP cycle
1.2 The Roles of metabolism
• Extract energy and reducing power
from the environment (photosynthesis
and oxidative degradation of nutrients);
• Generation (interconversion) of all the
biomolecules (small and large) for a
living organism (biosynthesis).
1.3 The General Features of
metabolism
• Occurs in linear, branched or circular pathways;
• Highly interconnected (“Every road leads to Rome”).
• Highly regulated to achieve the best economy
(“Balanced supply and demand”).
• The number of reactions is large (over 1000) and the
number of types of reactions is relatively small.
• Well conserved during evolution: reflecting the unity
of the life phenomena (“what happens in bacteria
happens in human being”).
Degradation is convergent
and energy releasing
异戊烯焦磷酸
乙酰辅酶A
草酰乙酸
柠檬酸
The citric
acid cycle
Synthesis is divergent
and energy consuming
Coenzyme A: the carrier of activated acyl groups
巯基乙胺
泛酸
Acetyl-CoA: the common degradative
product of sugar, fatty acids and
many amino acids
Metabolism:
The economy
The unity
The regulation
2. Things that will be covered
1). General principles for bioenergetics.
2). Oxidative degradation of fuels (glycolysis, boxidation, urea cycle, a-ketoacid oxidation, citric acid
cycle), generating NADH, FADH2, ATP, and CO2.
3). Oxidation of NADH and FADH2 by O2 and
generation of ATP and H2O (respiratory chains, ATP
synthase).
4). Photosynthsis (photophosphorylation and carbon
fixation).
5). Biosynthsis of DNA, RNA and Protein (replication,
repair, recombination, transcription, translation).
6). Regulation of metabolism.
Chapter 15
Glycolysis and
catabolism of
hexoses
Preparatory
Phase
Payoff
Phase
Chapter 16
The citric acid
cycle
The citric acid cycle
Or the Krebs cycle
Or Tricarboxylic acid cycle
Chapter 17
Oxidation of
fatty acids
The urea cycle
Chapter 18 Amino acid oxidation and
the production of urea
Chapter 18
Amino acid oxidation and
the production of urea
Chapter 19
Oxidative phosphorylation
And photophosphorylation
Oxidative
Phosphorylation
(0n inner membrane
of mitochondria)
Chapter 19
Oxidative phosphorylation and
photophosphorylation
Chapter 20
Carbohydrate biosynthesis
Chapter 20
Carbohydrate
biosynthesis
The Calvin Cycle
(CO2 fixation)
Chapter 21
Lipid biosynthesis
Chapter 21
Lipid biosynthesis
Chapter 22
Biosynthsis of amino acids, nucleotides, and related
molecules
Chapter 22 Biosynthesis of amino acids, nucleotides,
And related molecules
Chapter 23
Integration and hormonal
Regulation of mammalian
metabolism
Chapter 24
Genes and
chromosomes
Proposed way of coupling the
synthesis of the leading and
the lagging strand
The
loop
Chapter 25
DNA metabolism
The ABC
exinuclease
Cleaves at the eighth
phosphodiester bond
at the 5’ side of the lesion
Proposed model
for nucleotideexcision repair
in E.coli cells
Fourth or fifth phosphodiester
bond at the 3’ side of the lesion
Chapter 25
DNA metabolism
The strands
switch
positions
(by rotating the
recombinase)
Chapter 25 DNA metabolism
cut
Covalent
DNA-recombinase
intermediates
cut
The two yet-cut
strands are
cut at specific
sites and also
exchanged
Chapter 26 RNA metabolism
All 64
genetic
codes
Chapter 27
Protein metabolism
Chapter 27 Protein metabolism
The formation of
the Peptide bond is
probably catalyzed
by the 23S rRNA
ribozyme.
Chapter 28
Regulation of gene expression
The lactose operon in the induced
state (in the presence of an inducer)
Chapter 29
Recombinant
DNA technology
Recombinant DNA
can be generated by
using restriction
enzymes and ligase.
3. Understanding
Metabolism: a retrospect
3.1 Sugar degradation (glycolysis)
and synthesis
• 1897, Eduard Buchner, Cell-free fermentation
(Nobel Prize in 1907).
• Otto Fritz Meyerhof, conversion of glucose to lactic
acid in muscle and back to glucose in liver (Nobel
Prize in 1922).
• Sir Arthur Harden and Hans von Euler-Chelpin,
involvement of enzymes, coenzymes, and
phosphorylated intermediates (Nobel Prize in 1929).
• Carl Ferdinand Cori and Gerty Theresa Cori,
formation of glucose-1-phosphate from glycogen
and pyrophosphate by the action of phosphorylase
(Nobel Prize in 1947).
• Luis F. Leloir, UDP-glucose is the precursor for
glycogen synthesis (Nobel Prize in 1970).
• The whole glycolysis pathway (conversion of
glucose to pyruvate) was revealed by 1940.
3.2 Complete oxidation of fuels:
from two-carbon units to CO2
• Albert von Szent-Gyorgyi, plant acids, fumaric acid
(反丁烯二酸), malic acid (苹果酸) were not
consumed, but act as catalysts for the cellular
combustion process (Nobel Prize in 1937).
• Fritz Albert Lipmann, role of co-enzyme A and ATP
(Nobel Prize in 1953);
• Sir Hans Adolf Krebs, Acetyl-CoA and citric acid
cycle (柠檬酸循环) for complete oxidation twocarbon units (Nobel Prize in 1953).
3.3 Synthesis of ATP using energy
released from fuel oxidation
• Otto Heinrich Warburg, involvement of iron-containing
cytochromes (细胞色素) in cellular respiration (Nobel Prize
in 1931).
• Peter D. Mitchell, proposed the chemiosmotic theory（化学
渗透学说）to relate electron flow to ATP synthesis in all
organisms (Nobel Prize in 1978).
• Paul D. Boyer, John E. Walker, enzymatic mechanism for
ATP synthesis (Nobel Prize in 1997).
Dr. Paul D. Boyer
Nobel Prize in 1997
3.4 Lipid degradation and synthesis
• Konrad Bloch and Feodor Lynen, pathways for
cholesterol and fatty acid synthesis (Nobel Prize in
1964).
• Michael S. Brown and Joseph L. Goldstein,
regulation of cholesterol biosynthesis (Nobel Prize
in 1985).
3.5 Regulation of Metabolism
• Earl W. Sutherland, Jr., cAMP as the second
messager for hormones to regulate cell metabolism
(Nobel Prize in 1971).
• Alfred G. Gilman and Martin Rodbell, involvement
of membrane G-proteins in signal transduction of
hormones (Nobel Prize in 1994).
• Edmond H. Fischer and Edwin G. Krebs, regulation
of enzymatic activity by reversible phosphorylation
(Nobel Prize in 1992).
Dr. Edmond H. Fischer
Nobel Prize in 1992
3.6 Photosynthesis
• Hans Fischer, constitution of chlorophyll (叶绿素)
and its similarity to heme (Nobel Prize in 1930).
• Melvin Calvin, Calvin cycle for CO2 assimilation
(Nobel Prize in 1961).
• Johann Deisenhofer, Robert Huber, and Hartmut
Michel, 3-D structure of a Photosynthetic reaction
center from a purple bacterium (Nobel Prize in
1988).
3.7 DNA, RNA and Protein synthesis
• Severo Ochoa and Arthur Kornberg, enzymatic
synthesis of RNA and DNA (Nobel Prize in 1959).
• Marshall W. Nirenberg, Har Gobind Khorana,
interpretation of the genetic codes in protein
synthesis (Noble Prize in 1968).
• Francois Jacob, Andre Lwoff, and Jacques Monod,
Mechanisms to switch genes one and off in
prokaryotes (Nobel Prize in 1965).
• David Baltimore, Renato Dulbecco, and Howard
Martin Temin, enzymatic RNA-dependent DNA
synthesis in tumor viruses (Nobel Prize in 1975).
• Barbara McClintock, mobile genetic elements or
transposons (Nobel Prize in 1983).
• Susumu Tonegawa, genetic principle for the
generation of antibody diversity (Nobel Prize in
1987).
• Sidney Altman and Thomas R. Cech, RNA catalyzed
RNA processing (Ribozyme，核酶) (Nobel Prize in
1989).
• Richard J. Roberts and Philip A. Sharp, eukaryotic
genes are split and have to be spliced (剪接） after
transcription (Noble Prize in 1993).
• Gunter Blobel, intrinsic signals govern protein
localization (Nobel Prize in 1999).
David Baltimore
Nobel Prize in 1975
How to study Biochemistry II
• Compare and relate the chemical reactions (the
substrates, the products and the type of conversion)
enzymes, coenzymes, physiological roles, ways of
regulation involved, etc. (This must be
similar/related to that!)
• Understand the classical experiments and thoughts
that led to the revelation of the knowledge
described (why was one awarded the Nobel Prize?).
• Be aware with the degree of speculativeness on
certain models (nothing is 100% certain in science).
• Understand the aspects that need further studies
(how could I win a Nobel Prize?)
Scoring for this course
• Tests and attendance: 10%;
• Oral presentation of a research article (from
a list of references): 5%;
• Midterm exam: 25%;
• Final Exam: 60%.