Biochemistry I
Instructor,Dr,Fan Jiang(江凡 )
Class schedule,Monday 1:30--3:05 pm
Wednesday 3:20--4:55 pm
Place,Biology Building 214
Teaching assistant,
Requirement,Write in English with correct grammar,
Expressions made of only keywords piled together are
NOT acceptable,Leave no chance for guessing.
Course Organization
(a metaphor to a play)
Static part (静态部分 ):
Dynamic part (动态部分 ):
To introduce characters,roles,
scenes,backgrounds,
settings,…etc (structure and
function)
To present dialogues,actions,
stories,and drama (interesting
and exciting)
Rationale for this organization
1,Natural for systematic studies and learning
(as opposed to casual understanding).
2,Pedagogic purposes (teaching purposes),
easy to add and delete.
3,Organization of our textbook (Lehninger’s is
very detailed and well illustrated,good for
reading and self-learning,Stryer’s more
advanced but less detailed,Zubay’s may be in
the middle).
4,Our traditional organization.
Goals of Studying Biochemistry
1,To introduce the language of biochemistry,with
careful explanations of the meaning,origin,and
significance of terms.
2,To provide a balanced understanding of the
physical,chemical,and biological context in
which each biomolecule,reaction,and pathway
operates.
3,To project a clear and repeated emphasis on
major themes,especially those relating to
evolution,thermodynamics,regulation,and the
relationship between structure and function.
4,To explain and to place in context the most
important techniques that have brought us to our
current understanding of biochemistry (key
experiments)
5,To sustain the student’s interest by developing
topics in a logical and stepwise manner; taking
every opportunity to point out connections between
processes; identifying gaps in our knowledge that
promise to challenge future generations of scientists;
supplying the historical context of selected major
discoveries,when such context is useful; and
highlighting the implications of biochemical
advances for society (preparing you for research
and discovery and other adventures you may
undertake in the future).
Chapter 0 Introduction
1,The main features of the living matters
1.1 structurally complicated and highly
organized
1.2 metabolize--extract,transform,and use
nutrients and energy from their environment
1.3 respond (adapt and survive) by finding
energy and raw materials through interacting
with their surroundings
1.4 self replicate and self assembly (reproduce
and perpetuate)
1.5 evolve and diversify
The origin of the universe
(a) microscopic
complexity
(b) energy
comsumption,
food chain
(c) reproduction
Garden of Eden (diversity and unity)
2,What is Biochemistry?
The study of the molecular basis of life or
understanding life phenomena in chemical
terms,
It is the combination of biology and chemistry
or the application of chemical principles to
understanding biology.
3,What are the questions for biochemists to answer?
3.1 What are the biomolecules (composition and
structure)?
3.2 How do biomolecules act and interact
(conferring the remarkable features of living
organisms)?
3.3 How are the biomolecules synthesized
(biosynthesis)?
3.4 How is energy generated and consumed
(energy metabolism,its source and fate)?
3.5 How are the myriad of biochemical reactions
regulated (the coordination problem,the network
of control)?
3.6 What is the carrier of genetic information and
how is it expressed and transmitted (information
pathway)? (preserved faithfully)
3.7 How do cells and organisms grow,differentiate,
and reproduce?
3.8 What is the molecular basis of evolution?
3.9 What makes living organisms so diversified?
(advantages,purposes and natural tendencies)
3.10 How do we make use of life and knowledge
about life for the benefits of human being
(biotechnology,quality of life,societal welfare)?
4,A Brief History of Biochemistry over the last 200
years (milestones)
1780s Antoine Lavoisier (French),Combustion of a candle is
similar to the respiration of animals,as both need O2,For the
first time a physiological process was explained with reference
to a nonliving mechanism.
1810s-1830s A major substance from animals and plants was
identified,composing of C,H,O,and N,The term,Protein”,
meaning the most important thing,was first used in 1838.
1850s-1890s Carbohydrates,lipids,and nucleic acids were
recognized,The term,biochemistry” was formed in the 1870s.
1890s Eduard Buchner (German),Cell free yeast extract
can ferment sugar to alcohol! Enzymes can function when
removed from the living cells! Rejected the vitalism theory!
1920s-1930s James Sumner,Enzymes are proteins.
1940s-1950s Avery and Hershey,DNA carries the genetic
information.
1950s Franklin,and Watson and Crick,DNA is a double
helix.
1960s Nirenberg,Genetic codes deciphered.
1980s Cech,RNA has catalytic activity (Ribosome).
5,Modern Biochemical Science
5.1 It has become the common language of biology,
concepts and approaches
5.2 It has learned much about the chemical mechanisms
of many central processes of life.
5.3 It has revealed the remarkable chemical unity under
the biological diversity,
5.3.1 Living organisms (e.g.,E.coli and human
beings) are very much alike at the microscopic and
chemical level.
5.3.2 The building blocks for the macromolecules
are the same.
5.3.3 The flow of genetic information is the same
(from DNA to RNA to protein).
5.4 It has profoundly influenced medicine (and
agriculture)
5.4.1 Molecular lesions causing various
genetic diseases have been revealed (e.g.,sickle-
cell anemia; cystic fibrosis).
5.4.2 Clinical diagnostics has been greatly
enriched.
5.4.3 Production of valuable proteins by
genetic engineering is made possible.
5.4.4 Rational design of new drugs
5.4.5 Generation of crops and domestic
animals with new (genetic makeup) features.
5.5 It has pioneered and developed some of the
crucial concepts and techniques to tackle the
most challenging and fundamental problems in
biology and medicine.
5.5.1 Mechanism of cell differentiation
and development
5.5.2 Causes of cancers
5.5.3 Molecular basis of memory,
thinking,and other functions of the brain.
6,How to Study
6.1 Examine the critical experiments leading to
major discoveries
6.2 Understand the major themes in biochemistry,
For example,what are the properties and
functions of noncovalent interactions,allosteric
regulation,and etc.
6.3 Get a sense of developing and evolving
concepts and knowledge,That is what we are
learning today may be modified or corrected
tomorrow (e.g.,concept of enzyme).
Chapter 1 Cell Structure
1,The cell doctrine (accepted in the 1850s)
1.1 All living organisms are made up of cells,
the smallest unit of living matters,
(It is both the structural and functional unit,
The human body contains at least 1014 cells.)
1.2 Cells are capable of self-reproduction.
2,Most cells are microscopic in size
2.1 animal and plant cells,10-30 microns in diameter
(micro-meter,10-6 meter); bacteria,1-2 microns long;
mycoplasma,300nm (nanometer,10-9 m).
2.2 The requirement of optimal surface area to volume
ratio probably limits the cell sizes,
2.2.1 Most cells distribute oxygen and nutrient
molecules throughout the cell volume through
diffusion,The rate of diffusion in acqueous systems
limit the extent of the volume accessible,The larger
surface area to volume ratio (smaller spherical cells)
facilitate the accessibility,Highly convoluted (folded)
surfaces facilitate the accessibility (fig,2-3),An
exception is cytoplasmic streaming (energy facilitated
distribution).
(a) In cells of the intestinal mucosa,the plasma membrane facing the intestinal lumen is folded into
microvilli,increasing the area for absorption of nutrients.
A dividing E,coli大肠杆菌
Dividing Saccharomyces cerevisiae (baker’s yeast) cells
3,Evolution and Structure of Prokaryotic Cells (the
best-studied prokaryotic cell is Escherichia coli)
3.1 It is surrounded by a cell envelop,consisting of (I)
Outer membrane (gram-negative bacteria only),
permeable to small molecules such as sugars and
amino acids; (ii) Inner plasma membrane,a selective
barrier,made of many proteins (about 200 kinds)
floating in a lipid脂 bilayer such as receptors and
transporters; (iii) Periplasmic space,between the
plasma and outer membranes; (iv) Cell Wall,a
peptidoglycan layer.
3.2 It has a noncompartmentalized cytoplasm细胞质
(the part between the plasma membrane and
nucleoid),containing the following components:
3.2.1 Ribosomes核糖体, the largest particles in
the cytoplasm,the protein synthesis machine;
smaller but structurally and functionally similar to
those of eukaryotic真核 cells.
3.2.2 Proteins (including enzymes),metabolites,
cofactors,and inorganic ions.
3.2.3 Plasmids细胞质粒, small circular DNA
molecules,often confer resistance to toxins and
antibiotics; they replicate independently,and are
used as vectors in genetic engineering.
3.3 Nucleoid核质体（染色体团）, the area
where the highly packed single circular
chromosomal DNA locates,without the
surrounding membrane,but believed to be
attached to the membrane.
3.4 It has one or more long flagella鞭毛
extending from the surface,a complex rotary
motor that propels the cell (swim).
4,Major Structural Features of
Eukaryotic真核的 Cells
4.1 Eukaryotic organisms include algae藻类,
protozoa原生动物,fungi真菌,plants,and animals.
4.2 An extended intracellular membrane system
compartmentalizes分隔 the cytoplasm细胞质 of
an eukaryotic cell,forming various organelles细
胞器, They are
a nucleus细胞核
an endoplasmic reticulum 内质网 (ER) system
a Golgi apparatus高尔基体
many mitochondria线粒体
lysosomes溶酶体 (or vacuoles液泡 in plants)
peroxisomes过氧化物酶体,and chloroplasts叶绿体
(in plants)
4.3 Nucleus
4.3.1 It is the place where genetic
information carrier (DNA) is stored.
4.3.2 It is surrounded by an nuclear
envelop consisting of double membranes with
specialized complex pores facilitating the
material passage,The outer layer is continuous
with the ER membrane system.
4.3.3 DNA is condensed螺旋 (compressed)
about 10 million fold (in the linear dimension)
in a human chromosome 染色体 (becoming the
visible rods杆状 before cell divides).
4.3.4 DNA wraps around histone组蛋白
proteins to form nucleosomes,which further
pack into chromatin fibers,… (other levels of
packaging)…,and eventually in chromatin 染色
质,
4.3.5 The dense area (under EM) in a
nucleus is called the nucleolus核仁,where
rRNA is actively synthesized and assembled
with proteins into ribosome核糖体 subunits
(particles).
Nuclear pores
nucleolus
4.4 Endoplasmic Reticulum (ER)内质网
4.4.1 It is a netlike continuous membrane
system consisting of tubes and flattened sacs囊
(cisternae) extending through the cytoplasm细
胞质 (like a labyrinth 迷宫 ),forming an
enclosed lumen腔,
4.4.2 The ribosomes核糖体 that synthesize
proteins for secretion分泌 or specific targeting
are attached to the cytoplasmic surface of ER,
forming the rough ER (RER) structure.
4.4.3 Smooth ER (often tubular) is usually
the site for lipid synthesis and abundant in some
specialized cells functioning in detoxification
(liver),and the site for Ca2+ storage (skeletal
muscle).
4.4.4 Smooth ER often generates transport
vesicles泡囊 that fuse with other membrane
systems in the cell (usually the Golgi apparatus
for specific targeting).
4.5 Golgi Apparatus
4.5.1 It consists of a stack of flattened
membrane cisternae内质网液泡 surrounded by
many small vesicles.
4.5.2 It is structurally and functionally
asymmetric,with the cis side neighboring the ER
and the trans side facing the plasma membrane.
4.5.3 Proteins and lipids move through the
Golgi apparatus,entering from the cis side and
exiting from the trans side,During this process,
they are extensively modified,e.g.,glycosylated
糖基化,sulfated硫酸化,phosphorylated磷酸化,
etc.
4.5.4 The small vesicles serve as
transportation tools.
4.5.5 The newly synthesized proteins are
“addressed” for their destinations such as various
organelles,plasma membranes,and secretion to
extracelluar matrix,(sorting and targeting)
4.5.6 It is the place that supplies new cell
walls and membranes after cell division in plants
(so it is usually more extended,named as
dictyosome高尔基体 ).
4.6 Mitochondria线粒体
4.6.1 It is surrounded by two membranes,a
smooth outer membrane and an infolded inner
membrane (forming many cristae突起 ).
4.6.2 The space surrounded by the inner
membrane,called matrix,is gel凝胶 like and contains
hundreds of enzymes catalyzing the energy yielding灵
活的 reactions.
4.6.3 The energy carrier (ATP) is generated on
the inner membrane (ATP synthase合酶,a H+ pump)
4.6.4 It contains its own DNA,RNA,ribosomes核
糖体 (in the matrix)! It duplicates itself when cell
divides.
4.7 Lysosomes溶酶体
4.7.1 They are small spherical vesicles
surrounded by a single membrane,and are
generated from the Golgi apparatus.
4.7.2 They do not have any structural
characteristics and are identified by staining for
specific enzymes (usually acid phosphatase磷酸
酶 ).
4.7.3 It contains all kinds of acidic
hydrolytic水解 enzymes capable of digesting消
化 all four major biomolecules (proteins,nucleic
acids,carbohydrates,and lipids脂 )
4.7.4 It functions as the recycling center
of a cell (hydrolyzes biomolecules collected
through endocytosis内吞作用,phagocytosis吞
噬作用,or autophagy自吞噬 )
4.7.5 Vacuoles液泡 in plant cells play
similar recycling roles.
4.8 Peroxisomes过氧化物酶体
4.8.1 They are morphologically形态上 similar to
lysosomes溶酶体,also being single-membrane
surrounded particles微粒,
4.8.2 They are specialized in carrying out
oxidative reactions using molecular oxygen (O2),
generating damaging free radicals and hydrogen
peroxide过氧化氢 (H2O2),which are appropriately
destroyed by catalases过氧化氢酶,
4.8.3 In germinating培养 plant cells,the
glyoxylate乙醛酸 cycle,converting转变 the stored fats
into carbohydrates,occurs in the peroxisomes过氧化物
酶体 (thus also named as glyoxysomes乙醛酸循环体 ).
Communication across membranes
4.9 Chloroplasts叶绿体
4.9.1 They are structurally and
functionally similar to mitochondria线粒体,
also surrounded by two membranes and
transforming energy (from sunlight to
chemical energy).
4.9.2 But the inner membrane does not
form infoldings,instead,there is a third
membrane system forming a set of flattened
disclike sacs囊,named thylakoids类囊体,
4.9.3 Many thylakoids are piled up to
form a granum 叶绿体基粒 (grana).
4.9.4 The space between the inner
membrane and the thylakoid membrane,named
as the stroma基质,is very similar to the matrix in
mitochondria线粒体,containing various enzymes
involved in photosynthesis光合作用,
4.9.5 Chloroplasts叶绿体,like
mitochondria线粒体,contain their own DNA,
RNA,and ribosomes核糖体 in the stroma.
4.10 The endosymbiont内共生体 hypothesis假说
4.10.1 Mitochondria线粒体 and chloroplasts
evolved进化 from aerobic需氧的 and photosynthetic
bacteria that took up endosymbiotic内共生 residence (by
engulfing) in early eukaryotic真核的 cells more than a
billion years ago.
4.10.2 The main evidence supporting this
hypothesis,
4.10.2.1 similarity in sizes
4.10.2.2 striking similarity in some enzymes
involved in oxidative phosphorylation磷酸化作用
4.10.2.3 similarity in ribosomes (both in size
and antibiotic抗生素 sensitivity).
4.10.2.4 extensive广泛的 similarity in DNA
sequences.
4.10.3 There is no obvious evolutionary advantage
for the modern mitochondria线粒体 and
chloroplasts叶绿体 to still keep their own genetic
system,which is costly to maintain,Therefore,the
host system is used in endosymbiont内共生
existence.
4.10.4 The organelle’s细胞器 genetic systems are
probably an evolutionary dead end,It is because
the organelles did not have the chance (or the need,
if that matters) to complete the transfer of their
genes into the eukaryotic真核 nucleus.
4.11 The cytoskeleton细胞骨架 system
4.11.1 A dynamic (changing as needed)
network of protein filaments extends throughout
the cytoplasm细胞质 of an eukaryotic真核 cell.
4.11.2 It controls cell shapes,motility游动性,
intracellular organization,and cell division分裂,
4.11.3 This structure was discovered in the
1970s using high-voltage electron microscopes,
before which it was believed that the cytosol细胞质
溶胶 was an unorganized mixture of biomolecules.
4.11.4 These protein filaments can be divided
into three groups,actin肌动蛋白 filaments or formerly
microfilaments(~7 nm in diameter),microtubules微管
(~25 nm),and intermediate filaments(~10 nm).
4.11.5 The actin filament contains two chains of
globular球形的 actin molecules twisted one another in a
helical螺旋状的 manner,The actin monomers单体 assemble
and disassemble,Many proteins(e.g.,fodrin胞衬蛋白,fil-
amin细丝蛋白、肌动蛋白 )can specifically bind to actin to org-
anize its structure(crosslinking,severing,capping)and
to affect its function.Cytochalasins细胞分裂抑制素 (fungi真菌
alkaloids生物碱 )blocks actin polymerization聚合作用 and
inhibits cytokinesis细胞分裂,phagocytosis吞噬作用,amoe-
boid变形虫状的 movement,but not chromatid染色单体
segregation分离 (microtubules微管 ).
4.11.5 (cont’d) Actin filaments act as tracks
for cytoplasmic streaming,with many organelles
and vesicles小泡 moving towards one direction,
Actin filaments are rich and important in skeletal
muscles,intestinal microvilli微绒毛,etc,Actin is the
most abundant protein in most eukaryotic真核 cells.
4.11.6 A microtubule is a hollow cylinder (of
~200 nm to 25 nm in length) consisting of 13 rows
of tubulin微管蛋白 dimers二聚体 (fig.).
4.11.6.1 Microtubules usually radiate
out from a microtubule organizing center (two
centrioles中心粒 in animal cells) and serve as
tracks for intracellular movements.
4.11.6.2 Colchicine,a poisonous
plant alkaloid (inhibitor),causes mitotic spindle
to disappear and blocks cell mitosis at the
metaphase stage (blocking polymerization).
4.11.6.3 Microtubules and
associated proteins are responsible for the
motion of cilia (e.g.,on trachea and oviduct) and
eukaryotic flagella (sperm tail,some protists
such as trypanosomes).
4.11.7 Intermediate filaments (IF) are
strong,ropelike绳状的 polymers of fibrous proteins
that resist stretch and play a structural or
tension-bearing role.
4.11.7.1 They were thought to be
derived from already identified cytoskeleton细胞骨
架 elements like microtubules and actin filaments.
4.11.7.2 Different IF proteins (e.g.,
vimentin波形蛋白 in endothelial内皮 cells,desmin结蛋白
in muscle cells,keratins in certain epidermal cells
of vertebrates) are found in different cell types.
4.11.7.3 IF made of keratins are the
main components of hair,nails,and horns.
Different
organizations
ATP hydrolysis and cycles of conformational changes
A gallery of structurally and functionally
differentiated cells
Secretory
cell of the
Pancreas
胰腺
Portion of a skeletal muscle cell
Collenchyma cells of a plant stem茎
Human sperm cells
Mature human erythrocytes
Human embryo at the two-cell stage
In animal cells
Water-tight
seal
Reinforced by
Cytoskeletons
细胞骨架
Flow of ions
and electrical
Currents电流
In plants,
passage for
metabolites and
proteins
5,A rough analogy between the structure and
function of the cell and the human society
5.1 Nucleus,the highest administrative section of the
society where the blueprint of the society is kept.
5.2 Mitochondria and chloroplasts,the power plant.
5.3 Golgi Apparatus,the post office
5.4 Cytoskeleton system,the highways (transportation)
5.5 Lysosomes,the recycling center
5.6 ER,the training and education center
5.7 Plasma membrane,the border line
5.8 Like the human society,the cytoplasm is crowded,
highly organized,and dynamic.
6,Viruses are parasites of cells
6.1 Viruses are supramolecular complexes that
can replicate themselves in appropriate host cells.
6.1.1 Viruses usually consist of a nucleic
acid molecule surrounded by a protective protein
shell,and in some cases,also a membrane envelop.
6.1.2 Viruses exist as nonliving particles
(virions) with specific structures and
compositions when present outside their host cells
6.2 Hundreds of different viruses have been
discovered and,according to their host range,are
usually classified as bacteria viruses (bacteriophage,
or phage),animal viruses,and plant viruses.
6.3 Some viruses cause diseases to their hosts.
6.4 Biochemists have learned much about how genetic
information is duplicated and expressed by studying
viruses due to their simplicity.
6.5 Viruses are very likely evolved after cells appeared,
Most viruses probably evolved from plasmids (or
transposons,introns,…etc).
A gallery of viruses
Turnip yellow mosaic virus (spherical),tobacco mosaic
virus (long cylinder),and bacteriophage T4 (spidery legs)
HIV leaving an infected T lymphocyte of
the immune system
Filamentous phage fd
Molecular surface model of the canine
parvovirus
Human poliovirus (type 2),a picornavirus
Bacteriophage fX174
7,Biochemical studies of cells
7.1 Representative homogeneous viruses,cells,tissues,
and organisms are usually studied for understanding
the chemical basis of life.
7.2 Various parts of the cell are separated after being
carefully broken,Usually differential and isopycnic
centrifugations are used.
7.3 Individual biomolecules can be further purified and
studied using modern physical and chemical methods.
7.4 What is true in vitro may not be true in vivo!
Deducing what might be happening in a living
organism from observations of in vitro studies has to be
practiced with great caution!
Instructor,Dr,Fan Jiang(江凡 )
Class schedule,Monday 1:30--3:05 pm
Wednesday 3:20--4:55 pm
Place,Biology Building 214
Teaching assistant,
Requirement,Write in English with correct grammar,
Expressions made of only keywords piled together are
NOT acceptable,Leave no chance for guessing.
Course Organization
(a metaphor to a play)
Static part (静态部分 ):
Dynamic part (动态部分 ):
To introduce characters,roles,
scenes,backgrounds,
settings,…etc (structure and
function)
To present dialogues,actions,
stories,and drama (interesting
and exciting)
Rationale for this organization
1,Natural for systematic studies and learning
(as opposed to casual understanding).
2,Pedagogic purposes (teaching purposes),
easy to add and delete.
3,Organization of our textbook (Lehninger’s is
very detailed and well illustrated,good for
reading and self-learning,Stryer’s more
advanced but less detailed,Zubay’s may be in
the middle).
4,Our traditional organization.
Goals of Studying Biochemistry
1,To introduce the language of biochemistry,with
careful explanations of the meaning,origin,and
significance of terms.
2,To provide a balanced understanding of the
physical,chemical,and biological context in
which each biomolecule,reaction,and pathway
operates.
3,To project a clear and repeated emphasis on
major themes,especially those relating to
evolution,thermodynamics,regulation,and the
relationship between structure and function.
4,To explain and to place in context the most
important techniques that have brought us to our
current understanding of biochemistry (key
experiments)
5,To sustain the student’s interest by developing
topics in a logical and stepwise manner; taking
every opportunity to point out connections between
processes; identifying gaps in our knowledge that
promise to challenge future generations of scientists;
supplying the historical context of selected major
discoveries,when such context is useful; and
highlighting the implications of biochemical
advances for society (preparing you for research
and discovery and other adventures you may
undertake in the future).
Chapter 0 Introduction
1,The main features of the living matters
1.1 structurally complicated and highly
organized
1.2 metabolize--extract,transform,and use
nutrients and energy from their environment
1.3 respond (adapt and survive) by finding
energy and raw materials through interacting
with their surroundings
1.4 self replicate and self assembly (reproduce
and perpetuate)
1.5 evolve and diversify
The origin of the universe
(a) microscopic
complexity
(b) energy
comsumption,
food chain
(c) reproduction
Garden of Eden (diversity and unity)
2,What is Biochemistry?
The study of the molecular basis of life or
understanding life phenomena in chemical
terms,
It is the combination of biology and chemistry
or the application of chemical principles to
understanding biology.
3,What are the questions for biochemists to answer?
3.1 What are the biomolecules (composition and
structure)?
3.2 How do biomolecules act and interact
(conferring the remarkable features of living
organisms)?
3.3 How are the biomolecules synthesized
(biosynthesis)?
3.4 How is energy generated and consumed
(energy metabolism,its source and fate)?
3.5 How are the myriad of biochemical reactions
regulated (the coordination problem,the network
of control)?
3.6 What is the carrier of genetic information and
how is it expressed and transmitted (information
pathway)? (preserved faithfully)
3.7 How do cells and organisms grow,differentiate,
and reproduce?
3.8 What is the molecular basis of evolution?
3.9 What makes living organisms so diversified?
(advantages,purposes and natural tendencies)
3.10 How do we make use of life and knowledge
about life for the benefits of human being
(biotechnology,quality of life,societal welfare)?
4,A Brief History of Biochemistry over the last 200
years (milestones)
1780s Antoine Lavoisier (French),Combustion of a candle is
similar to the respiration of animals,as both need O2,For the
first time a physiological process was explained with reference
to a nonliving mechanism.
1810s-1830s A major substance from animals and plants was
identified,composing of C,H,O,and N,The term,Protein”,
meaning the most important thing,was first used in 1838.
1850s-1890s Carbohydrates,lipids,and nucleic acids were
recognized,The term,biochemistry” was formed in the 1870s.
1890s Eduard Buchner (German),Cell free yeast extract
can ferment sugar to alcohol! Enzymes can function when
removed from the living cells! Rejected the vitalism theory!
1920s-1930s James Sumner,Enzymes are proteins.
1940s-1950s Avery and Hershey,DNA carries the genetic
information.
1950s Franklin,and Watson and Crick,DNA is a double
helix.
1960s Nirenberg,Genetic codes deciphered.
1980s Cech,RNA has catalytic activity (Ribosome).
5,Modern Biochemical Science
5.1 It has become the common language of biology,
concepts and approaches
5.2 It has learned much about the chemical mechanisms
of many central processes of life.
5.3 It has revealed the remarkable chemical unity under
the biological diversity,
5.3.1 Living organisms (e.g.,E.coli and human
beings) are very much alike at the microscopic and
chemical level.
5.3.2 The building blocks for the macromolecules
are the same.
5.3.3 The flow of genetic information is the same
(from DNA to RNA to protein).
5.4 It has profoundly influenced medicine (and
agriculture)
5.4.1 Molecular lesions causing various
genetic diseases have been revealed (e.g.,sickle-
cell anemia; cystic fibrosis).
5.4.2 Clinical diagnostics has been greatly
enriched.
5.4.3 Production of valuable proteins by
genetic engineering is made possible.
5.4.4 Rational design of new drugs
5.4.5 Generation of crops and domestic
animals with new (genetic makeup) features.
5.5 It has pioneered and developed some of the
crucial concepts and techniques to tackle the
most challenging and fundamental problems in
biology and medicine.
5.5.1 Mechanism of cell differentiation
and development
5.5.2 Causes of cancers
5.5.3 Molecular basis of memory,
thinking,and other functions of the brain.
6,How to Study
6.1 Examine the critical experiments leading to
major discoveries
6.2 Understand the major themes in biochemistry,
For example,what are the properties and
functions of noncovalent interactions,allosteric
regulation,and etc.
6.3 Get a sense of developing and evolving
concepts and knowledge,That is what we are
learning today may be modified or corrected
tomorrow (e.g.,concept of enzyme).
Chapter 1 Cell Structure
1,The cell doctrine (accepted in the 1850s)
1.1 All living organisms are made up of cells,
the smallest unit of living matters,
(It is both the structural and functional unit,
The human body contains at least 1014 cells.)
1.2 Cells are capable of self-reproduction.
2,Most cells are microscopic in size
2.1 animal and plant cells,10-30 microns in diameter
(micro-meter,10-6 meter); bacteria,1-2 microns long;
mycoplasma,300nm (nanometer,10-9 m).
2.2 The requirement of optimal surface area to volume
ratio probably limits the cell sizes,
2.2.1 Most cells distribute oxygen and nutrient
molecules throughout the cell volume through
diffusion,The rate of diffusion in acqueous systems
limit the extent of the volume accessible,The larger
surface area to volume ratio (smaller spherical cells)
facilitate the accessibility,Highly convoluted (folded)
surfaces facilitate the accessibility (fig,2-3),An
exception is cytoplasmic streaming (energy facilitated
distribution).
(a) In cells of the intestinal mucosa,the plasma membrane facing the intestinal lumen is folded into
microvilli,increasing the area for absorption of nutrients.
A dividing E,coli大肠杆菌
Dividing Saccharomyces cerevisiae (baker’s yeast) cells
3,Evolution and Structure of Prokaryotic Cells (the
best-studied prokaryotic cell is Escherichia coli)
3.1 It is surrounded by a cell envelop,consisting of (I)
Outer membrane (gram-negative bacteria only),
permeable to small molecules such as sugars and
amino acids; (ii) Inner plasma membrane,a selective
barrier,made of many proteins (about 200 kinds)
floating in a lipid脂 bilayer such as receptors and
transporters; (iii) Periplasmic space,between the
plasma and outer membranes; (iv) Cell Wall,a
peptidoglycan layer.
3.2 It has a noncompartmentalized cytoplasm细胞质
(the part between the plasma membrane and
nucleoid),containing the following components:
3.2.1 Ribosomes核糖体, the largest particles in
the cytoplasm,the protein synthesis machine;
smaller but structurally and functionally similar to
those of eukaryotic真核 cells.
3.2.2 Proteins (including enzymes),metabolites,
cofactors,and inorganic ions.
3.2.3 Plasmids细胞质粒, small circular DNA
molecules,often confer resistance to toxins and
antibiotics; they replicate independently,and are
used as vectors in genetic engineering.
3.3 Nucleoid核质体（染色体团）, the area
where the highly packed single circular
chromosomal DNA locates,without the
surrounding membrane,but believed to be
attached to the membrane.
3.4 It has one or more long flagella鞭毛
extending from the surface,a complex rotary
motor that propels the cell (swim).
4,Major Structural Features of
Eukaryotic真核的 Cells
4.1 Eukaryotic organisms include algae藻类,
protozoa原生动物,fungi真菌,plants,and animals.
4.2 An extended intracellular membrane system
compartmentalizes分隔 the cytoplasm细胞质 of
an eukaryotic cell,forming various organelles细
胞器, They are
a nucleus细胞核
an endoplasmic reticulum 内质网 (ER) system
a Golgi apparatus高尔基体
many mitochondria线粒体
lysosomes溶酶体 (or vacuoles液泡 in plants)
peroxisomes过氧化物酶体,and chloroplasts叶绿体
(in plants)
4.3 Nucleus
4.3.1 It is the place where genetic
information carrier (DNA) is stored.
4.3.2 It is surrounded by an nuclear
envelop consisting of double membranes with
specialized complex pores facilitating the
material passage,The outer layer is continuous
with the ER membrane system.
4.3.3 DNA is condensed螺旋 (compressed)
about 10 million fold (in the linear dimension)
in a human chromosome 染色体 (becoming the
visible rods杆状 before cell divides).
4.3.4 DNA wraps around histone组蛋白
proteins to form nucleosomes,which further
pack into chromatin fibers,… (other levels of
packaging)…,and eventually in chromatin 染色
质,
4.3.5 The dense area (under EM) in a
nucleus is called the nucleolus核仁,where
rRNA is actively synthesized and assembled
with proteins into ribosome核糖体 subunits
(particles).
Nuclear pores
nucleolus
4.4 Endoplasmic Reticulum (ER)内质网
4.4.1 It is a netlike continuous membrane
system consisting of tubes and flattened sacs囊
(cisternae) extending through the cytoplasm细
胞质 (like a labyrinth 迷宫 ),forming an
enclosed lumen腔,
4.4.2 The ribosomes核糖体 that synthesize
proteins for secretion分泌 or specific targeting
are attached to the cytoplasmic surface of ER,
forming the rough ER (RER) structure.
4.4.3 Smooth ER (often tubular) is usually
the site for lipid synthesis and abundant in some
specialized cells functioning in detoxification
(liver),and the site for Ca2+ storage (skeletal
muscle).
4.4.4 Smooth ER often generates transport
vesicles泡囊 that fuse with other membrane
systems in the cell (usually the Golgi apparatus
for specific targeting).
4.5 Golgi Apparatus
4.5.1 It consists of a stack of flattened
membrane cisternae内质网液泡 surrounded by
many small vesicles.
4.5.2 It is structurally and functionally
asymmetric,with the cis side neighboring the ER
and the trans side facing the plasma membrane.
4.5.3 Proteins and lipids move through the
Golgi apparatus,entering from the cis side and
exiting from the trans side,During this process,
they are extensively modified,e.g.,glycosylated
糖基化,sulfated硫酸化,phosphorylated磷酸化,
etc.
4.5.4 The small vesicles serve as
transportation tools.
4.5.5 The newly synthesized proteins are
“addressed” for their destinations such as various
organelles,plasma membranes,and secretion to
extracelluar matrix,(sorting and targeting)
4.5.6 It is the place that supplies new cell
walls and membranes after cell division in plants
(so it is usually more extended,named as
dictyosome高尔基体 ).
4.6 Mitochondria线粒体
4.6.1 It is surrounded by two membranes,a
smooth outer membrane and an infolded inner
membrane (forming many cristae突起 ).
4.6.2 The space surrounded by the inner
membrane,called matrix,is gel凝胶 like and contains
hundreds of enzymes catalyzing the energy yielding灵
活的 reactions.
4.6.3 The energy carrier (ATP) is generated on
the inner membrane (ATP synthase合酶,a H+ pump)
4.6.4 It contains its own DNA,RNA,ribosomes核
糖体 (in the matrix)! It duplicates itself when cell
divides.
4.7 Lysosomes溶酶体
4.7.1 They are small spherical vesicles
surrounded by a single membrane,and are
generated from the Golgi apparatus.
4.7.2 They do not have any structural
characteristics and are identified by staining for
specific enzymes (usually acid phosphatase磷酸
酶 ).
4.7.3 It contains all kinds of acidic
hydrolytic水解 enzymes capable of digesting消
化 all four major biomolecules (proteins,nucleic
acids,carbohydrates,and lipids脂 )
4.7.4 It functions as the recycling center
of a cell (hydrolyzes biomolecules collected
through endocytosis内吞作用,phagocytosis吞
噬作用,or autophagy自吞噬 )
4.7.5 Vacuoles液泡 in plant cells play
similar recycling roles.
4.8 Peroxisomes过氧化物酶体
4.8.1 They are morphologically形态上 similar to
lysosomes溶酶体,also being single-membrane
surrounded particles微粒,
4.8.2 They are specialized in carrying out
oxidative reactions using molecular oxygen (O2),
generating damaging free radicals and hydrogen
peroxide过氧化氢 (H2O2),which are appropriately
destroyed by catalases过氧化氢酶,
4.8.3 In germinating培养 plant cells,the
glyoxylate乙醛酸 cycle,converting转变 the stored fats
into carbohydrates,occurs in the peroxisomes过氧化物
酶体 (thus also named as glyoxysomes乙醛酸循环体 ).
Communication across membranes
4.9 Chloroplasts叶绿体
4.9.1 They are structurally and
functionally similar to mitochondria线粒体,
also surrounded by two membranes and
transforming energy (from sunlight to
chemical energy).
4.9.2 But the inner membrane does not
form infoldings,instead,there is a third
membrane system forming a set of flattened
disclike sacs囊,named thylakoids类囊体,
4.9.3 Many thylakoids are piled up to
form a granum 叶绿体基粒 (grana).
4.9.4 The space between the inner
membrane and the thylakoid membrane,named
as the stroma基质,is very similar to the matrix in
mitochondria线粒体,containing various enzymes
involved in photosynthesis光合作用,
4.9.5 Chloroplasts叶绿体,like
mitochondria线粒体,contain their own DNA,
RNA,and ribosomes核糖体 in the stroma.
4.10 The endosymbiont内共生体 hypothesis假说
4.10.1 Mitochondria线粒体 and chloroplasts
evolved进化 from aerobic需氧的 and photosynthetic
bacteria that took up endosymbiotic内共生 residence (by
engulfing) in early eukaryotic真核的 cells more than a
billion years ago.
4.10.2 The main evidence supporting this
hypothesis,
4.10.2.1 similarity in sizes
4.10.2.2 striking similarity in some enzymes
involved in oxidative phosphorylation磷酸化作用
4.10.2.3 similarity in ribosomes (both in size
and antibiotic抗生素 sensitivity).
4.10.2.4 extensive广泛的 similarity in DNA
sequences.
4.10.3 There is no obvious evolutionary advantage
for the modern mitochondria线粒体 and
chloroplasts叶绿体 to still keep their own genetic
system,which is costly to maintain,Therefore,the
host system is used in endosymbiont内共生
existence.
4.10.4 The organelle’s细胞器 genetic systems are
probably an evolutionary dead end,It is because
the organelles did not have the chance (or the need,
if that matters) to complete the transfer of their
genes into the eukaryotic真核 nucleus.
4.11 The cytoskeleton细胞骨架 system
4.11.1 A dynamic (changing as needed)
network of protein filaments extends throughout
the cytoplasm细胞质 of an eukaryotic真核 cell.
4.11.2 It controls cell shapes,motility游动性,
intracellular organization,and cell division分裂,
4.11.3 This structure was discovered in the
1970s using high-voltage electron microscopes,
before which it was believed that the cytosol细胞质
溶胶 was an unorganized mixture of biomolecules.
4.11.4 These protein filaments can be divided
into three groups,actin肌动蛋白 filaments or formerly
microfilaments(~7 nm in diameter),microtubules微管
(~25 nm),and intermediate filaments(~10 nm).
4.11.5 The actin filament contains two chains of
globular球形的 actin molecules twisted one another in a
helical螺旋状的 manner,The actin monomers单体 assemble
and disassemble,Many proteins(e.g.,fodrin胞衬蛋白,fil-
amin细丝蛋白、肌动蛋白 )can specifically bind to actin to org-
anize its structure(crosslinking,severing,capping)and
to affect its function.Cytochalasins细胞分裂抑制素 (fungi真菌
alkaloids生物碱 )blocks actin polymerization聚合作用 and
inhibits cytokinesis细胞分裂,phagocytosis吞噬作用,amoe-
boid变形虫状的 movement,but not chromatid染色单体
segregation分离 (microtubules微管 ).
4.11.5 (cont’d) Actin filaments act as tracks
for cytoplasmic streaming,with many organelles
and vesicles小泡 moving towards one direction,
Actin filaments are rich and important in skeletal
muscles,intestinal microvilli微绒毛,etc,Actin is the
most abundant protein in most eukaryotic真核 cells.
4.11.6 A microtubule is a hollow cylinder (of
~200 nm to 25 nm in length) consisting of 13 rows
of tubulin微管蛋白 dimers二聚体 (fig.).
4.11.6.1 Microtubules usually radiate
out from a microtubule organizing center (two
centrioles中心粒 in animal cells) and serve as
tracks for intracellular movements.
4.11.6.2 Colchicine,a poisonous
plant alkaloid (inhibitor),causes mitotic spindle
to disappear and blocks cell mitosis at the
metaphase stage (blocking polymerization).
4.11.6.3 Microtubules and
associated proteins are responsible for the
motion of cilia (e.g.,on trachea and oviduct) and
eukaryotic flagella (sperm tail,some protists
such as trypanosomes).
4.11.7 Intermediate filaments (IF) are
strong,ropelike绳状的 polymers of fibrous proteins
that resist stretch and play a structural or
tension-bearing role.
4.11.7.1 They were thought to be
derived from already identified cytoskeleton细胞骨
架 elements like microtubules and actin filaments.
4.11.7.2 Different IF proteins (e.g.,
vimentin波形蛋白 in endothelial内皮 cells,desmin结蛋白
in muscle cells,keratins in certain epidermal cells
of vertebrates) are found in different cell types.
4.11.7.3 IF made of keratins are the
main components of hair,nails,and horns.
Different
organizations
ATP hydrolysis and cycles of conformational changes
A gallery of structurally and functionally
differentiated cells
Secretory
cell of the
Pancreas
胰腺
Portion of a skeletal muscle cell
Collenchyma cells of a plant stem茎
Human sperm cells
Mature human erythrocytes
Human embryo at the two-cell stage
In animal cells
Water-tight
seal
Reinforced by
Cytoskeletons
细胞骨架
Flow of ions
and electrical
Currents电流
In plants,
passage for
metabolites and
proteins
5,A rough analogy between the structure and
function of the cell and the human society
5.1 Nucleus,the highest administrative section of the
society where the blueprint of the society is kept.
5.2 Mitochondria and chloroplasts,the power plant.
5.3 Golgi Apparatus,the post office
5.4 Cytoskeleton system,the highways (transportation)
5.5 Lysosomes,the recycling center
5.6 ER,the training and education center
5.7 Plasma membrane,the border line
5.8 Like the human society,the cytoplasm is crowded,
highly organized,and dynamic.
6,Viruses are parasites of cells
6.1 Viruses are supramolecular complexes that
can replicate themselves in appropriate host cells.
6.1.1 Viruses usually consist of a nucleic
acid molecule surrounded by a protective protein
shell,and in some cases,also a membrane envelop.
6.1.2 Viruses exist as nonliving particles
(virions) with specific structures and
compositions when present outside their host cells
6.2 Hundreds of different viruses have been
discovered and,according to their host range,are
usually classified as bacteria viruses (bacteriophage,
or phage),animal viruses,and plant viruses.
6.3 Some viruses cause diseases to their hosts.
6.4 Biochemists have learned much about how genetic
information is duplicated and expressed by studying
viruses due to their simplicity.
6.5 Viruses are very likely evolved after cells appeared,
Most viruses probably evolved from plasmids (or
transposons,introns,…etc).
A gallery of viruses
Turnip yellow mosaic virus (spherical),tobacco mosaic
virus (long cylinder),and bacteriophage T4 (spidery legs)
HIV leaving an infected T lymphocyte of
the immune system
Filamentous phage fd
Molecular surface model of the canine
parvovirus
Human poliovirus (type 2),a picornavirus
Bacteriophage fX174
7,Biochemical studies of cells
7.1 Representative homogeneous viruses,cells,tissues,
and organisms are usually studied for understanding
the chemical basis of life.
7.2 Various parts of the cell are separated after being
carefully broken,Usually differential and isopycnic
centrifugations are used.
7.3 Individual biomolecules can be further purified and
studied using modern physical and chemical methods.
7.4 What is true in vitro may not be true in vivo!
Deducing what might be happening in a living
organism from observations of in vitro studies has to be
practiced with great caution!
