Download Chap1 Overview of Biological Systems

Chap 1 Overview of Cellular Biology
I. Cell Components
Introduction

Mainly composed of high MW polymeric compounds—proteins, nucleic acids,
polysaccharides (e.g. glycogen), lipids (fats), etc.

Also contain metabolites in the form of inorganic salts (NH4+, PO3-, K+, Ca2+, Na+, SO42), metabolic intermediates (e.g. pyruvate, acetate) and vitamins.

The cellular macromolecules are functional when in the proper 3-D configuration.
1. Amino Acids and Proteins

Proteins are the most abundant organic molecules in the living cells (40-70% dry weight)

Protein functions:
Protein function
Examples
structural
Tubulin, actin, collagen
catalytic
Enzymes (e.g. RNA polymerase)
transport
Ion channel, glucose transporter, hemoglobin
regulatory
Growth factor, insulin
protective
Antibodies, thrombin

Proteins are polymers built from amino acids monomers. There are 20 a.a. in natural
proteins1. R, the side chain.
H
H2N
C
COOH
R
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Selenocysteine and pyrrolysine (not found in eukaryotes) are also considered a.a. in proteins, but these two are not encoded
by the universal genetic code. They are incorporated into proteins by unique synthetic mechanism.
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Polypeptide:
The condensation reaction between two a.a. forms a peptide bond
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
The continuous polymerization results in the formation of a polypeptide chain.

The polypeptide is planar. The polypeptide
chain can fold into proper 3-D structure (into
4 levels, see Appendix).

Primary structure: Linear sequence of
the polypeptide chain.
Contributes to the
structure and function of the protein.
e.g. Met-Val-Glu-Thr
Secondary structure: formed by Hbonding between residues not far away.

Tertiary structure: a result of interactions
between R groups widely separated. R
groups may interact by disulfide bond,
also the hydrophobic interactions are
important

Quaternary structure: only for proteins
with > 1 polypeptide chains
e.g. hemoglobin: 4 subunits associate to
form a quaternary structure.
e.g. immunoglobulin
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2. Lipids:

Hydrophobic, insoluble in water, but soluble in nonpolar solvents (e.g. benzene,
chloroform and ether)

Fatty acids are the major components in lipids

Examples of lipids

Lipopolysaccharides (LPS):

A major constituent on the outer membrane of Gram- bacteria (LPS is the so called
endotoxin that elicits symptoms characteristic of infections caused by bacteria, it cannot be destroyed with heat even
though such treatment kills the bacteria, thus manufacturers of intravenous solutions must be very cautious to ensure
that their solutions are not contaminated with bacteria, or even cell wall fragments.

Made of saturated fatty acids, polysaccharides and protein

Cells can alter the mix of lipids in the membrane to compensate for changes in
temperature or to increase their tolerance to the chemical agents (e.g. ethanol)

Fat: (biological fuel-storage molecules): saturated (solid fats), unsaturated (liquid oils)
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
Phospholipid:
glycerol
nonpolar
polar head+nonpolar tail amphipathic naturecan self-assemble into lipidbilayer.

Steroids: a hormone that regulates animal
development and metabolism, share a basic 4-ring
skeleton

cholesterol (膽固醇): precursor for many
steroids (e.g. estrogen 雌激素), existing
in the membranes of animal tissues.

Cortisone (可體松): a hormone that can
regulate carbohydrates, an antiinflammatory agent to treat rheumatoid
arthritis (類風濕性關節炎).(來自腎上腺皮質)
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3. Carbohydrates

Key role as structural (e.g. glycosaminoglycan in extracellular matrix) and storage
components (can serve as energy source).
Monosaccharides: smallest carbohydrates (3-9 carbon atoms)
-ose  sugar
-ase  enzyme

triose (3-carbon): dihydroxyacetone
O
CH2OH-C-CH2OH

hexose (6 carbon): All hexasoses have the same chemical formula (C6H12O6) and
contain an aldehyde or keto group.

pentose (5-carbon): ribose and deoxyribose
Disaccharides: formed by condensation of monosaccharides
Ex:

Sucrose: major sugar found in photosynthetic plants

lactose (乳糖):
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Polysaccharides:

Glycogen: a storehouse of surplus chemical
energy in most animals. Molecular weight 14 million. Most of the sugar units are joined
by (1->4)glycosidic bonds (type 2 bond).
Branch points are linked by (1->6)glycosidic
bonds (type 1 bond). When stored in cells,
glycogen is highly concentrated and appears as
dark-staining, irregular granules.

Starch: a storehouse of surplus chemical
energy in most plants. A mixture of amylose
(直鏈澱粉 joined by (1->4)glycosidic bonds
(type 2 bond)) and amylopectin (branched
starch). Molecular mass of amylose several
thousand to 500,000 Da (Da=mass of a
hydrogen atom).

Cellulose: The most abundant polysaccharide in the
world.
Long unbranched chain with D-glucose.
MW50,000
to
1
million.
by (1-
Joined
>4)glycosidic bonds (type 3 bond). The -linkage is
less prone to hydrolysis, so the breakdown of
cellulose remains a hurdle to the use of cellulose for
the production of biofuel or chemicals.

Chitin: poly(-1,4-N-acetyl-D-glucosamine) (幾丁
質 ): abundant polysaccharide present in the cell
walls or shells of animals.

Chitosan: poly(-1,4-D-glucosamine) (幾丁聚醣).
Chitin and chitosan have very good biocompatibility and are now widely used as nutrient
supplement, biomaterials (suture, artificial skin, carrier, etc.), enzyme immobilization.
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4. Nucleic Acids: DNA and RNA (Next chapter)
II. Cell Types

Living cells are divided into two classes: procaryotes (e.g. bacteria) and eucaryotes
(protozoa (原生動物，如草履蟲、阿米巴原蟲), fungi, plants and animals).
Procaryotes:

Classified as Gram+ and Gram- (can be distinguished by Gram staining)

Gram+: no outer membrane but with thick rigid cell wall containing multiple
layers of peptidoglycan (e.g. Bacillus (桿菌屬) subtilis).

Gram-: with outer membrane but thinner cell wall (e.g. Escherichia coli)

Note: the cells are named by genus (屬)+species (種), these words are Latin.
Same E. coli can have different substrains, which can be characterized by
following number, e.g. E. coli JM105.

E. coli:

0.5-3 m
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
inner and outer membranes are separated by a periplasmic space (periplasm) which
contains gel like fluid. All secreted proteins are contained within the periplasm
unless they are specifically translocated across the outer membrane.

ribosome: site of protein synthesis, composed of large and small subunits each
consisting of protein and rRNA.

chromosome: where DNA is

plasmid: autonomous small DNA, encodes miscellaneous functions, e.g. resistance
to antibiotics, special metabolisms…

Flagella: facilitate the movement of cells.
Peptidoglycan: the major component of bacterial cell wall
Components and structure of
peptidoglycan: Chemical
structure of N-acetylglucosamine
(NAG) and N-acetylmuramic acid
(NAM); the ring structures of the
two molecules are glucose.
Glycan chains are composed of
alternating subunits of NAG and
NAM joined by covalent bonds.
Adjacent glycan chains are crosslinked via their tetrapeptide
chains to create peptidoglycan.
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(a) Gram+ cell wall is characterized by a relatively thick layer of peptidoglycan. (b)
It is made up of many sheets of internnected glycan chains. These sheets are
internenected to make the thick peptidoglycan molecule.
The Gram- cell wall
has a very thin cell
wall surrounded by an
outer membrane. The
peptidoglycan layer is
made up of only one or
two sheets of glycan
chains. The outer
membrane is a typical
phospholipid bilayer,
except the outer leaflet
contains
lipopolysaccharide.
Porins span the
membrane to allow
specific molecules to
pass.


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Capsules are composed of polysaccharides
such as dextrans and glucans, taking the form
of tiny, short, hair-like structures or fibrils
and forming the network on the outside of the
cell wall.
Most capsules are a viscous layer that
envelopes the bacteria to facilitate the
attachment of bacteria to surfaces.
Note:
(1) Penicillin binds to penicillin-binding protein which involves in the peptidoglycan
synthesis and thus inhibits the cell wall synthesis.
(2) Lysozyme: breaks the bond linking NAM and NAG destroys the structural integrity
of the glycan chain.
Cell Membrane: mainly composed of phospholipids and proteins

Phospholipids form the lipid bilayer. Many proteins are anchored on the membrane,
serving various functions (e.g. receptors that can trigger downstream signaling upon
ligand binding, transporters (e.g. glucose transporter))
Eucaryotes:

5-10 times larger than procaryotes

Contain nucleus and cellular organelles. Some eucaryotes have cell walls (e.g. plant),
some don’t (e.g. animal cells, so animal cells are fragile, shear sensitive)
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
Cell membrane:
From Karp, G. (2002). Cell and Molecular Biology: Concepts and Experiments.

Nucleus: Surrounded by the nuclear membrane, which selectively allows for molecules
in and out of nucleus. Contains the following:

Chromosome: more than 1, each chromosome contains a single DNA molecule on
which a protein called Histone is attached.
Humans have 23 pairs of chromosomes; dogs 39 pairs; potatos,
24,; yeast, 17. Note: in sexual division, gametes (haploid) fuse to form zygote (diploid), normally there are 2 copies of each
chromosome to form a homologous pair.


Nucleolus: a factory where the cells’ ribosomes are assembled
Mitochondria: about the size of bacteria but have their own genome in the form of circular DNA, their own
tRNA and their own ribosomes,
thought to be evolved from invading bacteria; power house where
electron transport and oxidative phosphorylation occur. (C6H12O6+6O2 6CO2+ 6 H2O
G=-2823 KJ/mol)

Endoplasmic reticulum:
Rough ER: site of protein synthesis (ribosomes attach to rough ER)
Smooth ER: site of lipid synthesis

Golgi: responsible for sorting of proteins, site of protein glycosylation (addition of sugars)
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
Lysosomes:

are membrane-bound vesicles (pH 4.8) on the endocytic pathway (see Appendix);

contain some 40 digestive enzymes for the digestion of cellular waste products, fats,
carbohydrates, proteins, other macromolecules and invading substances.

Proteasomes:

In the nucleus and cytoplasm; a complex comprising proteases that can degrade
unneeded or damaged proteins by proteolysis

Can regulate the concentration of particular proteins and degrade misfolded proteins.
The degradation yields peptides of about 7-8 amino acids long, which can then be
further degraded into amino acids and used in synthesizing new proteins.

Peroxisomes: membrane bound vesicles that contain peroxidases that generate and
destroy hydrogen peroxide. H2O2+reduced substrate2H2O+oxidized substrate

Cytoskeleton:

Actin filament (microfilament): determines the shape of cell surface and is needed for
whole cell locomotion; allows cells to attach to an underlying substratum; enables
muscles to contract.

Microtubule: forms a bipolar mitotic spindle (紡錘) during cell division; forms motile
whips called cilia (纖毛) and flagella (鞭毛) on the cell surface; forms tightly aligned
bundles that determine the positions of organelles and direct intracellular transport
with the aid of other accessory proteins (e.g. motor proteins).

Intermediate filament: provides mechanical strength and resistance to shear stress.
Virus:

Non-living organism, has to rely on a host to replicate, very small (20-300 nm).

Can carry DNA or RNA as the genetic materials (cells carry DNA)

Causes of many diseases such as AIDS (HIV), influenza (influenza virus).

Basic virus structure: structural proteins form subunits and assemble into nucleocapsids
which have DNA or RNA packaged. Some viruses contain envelopes, and even spikes.
Some viruses carry their own enzyme for replication (e.g. vaccinia virus).
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3CD
Infection and Replication
1.
Attachment by receptors (not every cell has all receptors for all viruses)
2.
Penetration: virus particle enters the
cell (e.g. by endocytosis)
3.
Uncoat (release of DNA or RNA)
capsid disintegrates
4.
Viral protein synthesis (structural
proteins, regulatory proteins,
enzymes, etc.)
5.
DNA or RNA synthesis (shut down
cellular activities) (mostly in the
nucleus, some in the cytoplasm, e.g.
vaccinia virus)
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6.
Virus particle assembly (structural proteins assemble, incorporate nucleic acids and other
proteins)
7.
Virus release

Types of infection

Lytic infection: at a certain stage after infection, cells lyse.

Lysogenic infection: viral nucleic acids integrate into host chromosome and the host
cell may continue to survive.
Why need to know about virus?
1.
Viruses cause many diseases, it’s important to investigate the infection mechanisms to
block the virus multiplication and virus function, etc.
2.
Viruses have been used as tools in medicine and in biotechnology.

As vaccines: influenza vaccine

For protein production: baculovirus and vaccinia virus.

Gene therapy vectors: adenovirus, adeno-associated virus, retrovirus.
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IV. Appendix:
From Panel 16-1, Alberts, B., Johnson, A., Lewis, J., Raff,
M., Roberts, K., Walter, P. (2002) Molecular Biology of the
Cell, 4th Ed. Garland Science, New York.
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Endocytosis: a process by which cells absorb
molecules
(e.g. proteins) by engulfing them, including
clathrin-mediated endocytosis, caveolae,
macropinocytosis, and phagocytosis. Several
membrane compartments are involved: Early
endosomes, late endosome and lysosome. Early
endosomes (vesicles up to 1 µm in diameter) are often
located in the periphery of the cell and receive most of
types of vesicles coming from the cell surface. They
are principally sorting organelles where many ligands
dissociate from their receptors in the acid pH of the lumen and from which many of the receptors recycle
to the cell surface. Late endosomes: receive internalized material en route to lysosomes, usually from
early endosomes in the endocytic pathway, from trans-Golgi network in the biosynthetic pathway, and
from phagosomes in the phagocytic pathway. Late endosomes are acidic (approx. pH 5.5), and are thought
to mediate a final set of sorting events prior to delivery of material to lysosomes.
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(a)
(c)
(b)
(d)
Electron micrographs and schematic illustrations of viruses. (a) Bacteriophage Si
1. (b) Tobacco mosaic virus. (c) Enveloped virus with spikes. Top: Sindbis virus;
Bottom, influenza virus. (d) Tailed bacteriophage
References:
1.
2.
3.
4.
5.
Karp, G. (2002). Cell and Molecular Biology: Concepts and Experiments. 3rd Ed. John
Wiley &Sons. New York.
Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. (2002) Molecular
Biology of the Cell, 4th Ed. Garland Science, New York.
Shuler ML and Kargi F. (1992) Bioprocess Engineering: Basic Concepts. Prentice Hall
International, London.
Samuel, C.E. 2001. Antiviral actions of interferons. Clin. Microbiol. Rev. 14: 778-809.
Janeway CA, Travers P, Walport M, Shlomchik MJ. 2005. Immunobiology. New York:
Garland Science.
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