Gerald Karp
Cell and Molecular Biology
Fifth Edition
Chapter 1
CHAPTER 2 Part 1
The Chemical Basis of Life
Copyright © 2008 by John Wiley & Sons, Inc.
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Scientific spectrum
Cellular and Molecular Biology
Reductionist
Replaced by an equally strong
appreciation for the beauty and complexity
of the mechanisms underlying cellular
activity
1.1 The discovery of cells
Robert Hook : mid-1600s
Anton vanLeeuwenhoek : animalcules
M. Schleiden : 1830s
T. Schwann : 1839
R. Virchow : 1855
Cell Theory: 1. All organisms are composed of one or
more cells
2. The cell is the structural unit of life
3. Cells can raise only by a division from a preexisting cell
1.2 Basic properties of cells
1951 Johns Hopkins University:
Dr. George Gey cultured first human cell line
from HeLa cell (Henrietta Lacks) that are being
grown in the laboratory all around the world
Cells are highly complex and
organized
1. Levels of cellular and molecular
organization (same ancestor, only expression
is different)
2. Cells possess a genetic program and the
means to use it (3x1012 base pairs)
3. Cells are capable of producing more of
themselves
4. Cells acquire and utilize energy
5. Cells carry out a variety of chemical
reactions (metabolism)
6. Cells engage in numerous mechanical
activities
7. Cells are able to respond to stimuli
8. Cells are capable of self-regulation (Fig. 1.6)
9. Cells evolve
1.3 Two fundamentally
different classes of cells
3.5 billion years: Cyanobacteria
1.5 billion years: Eukaryotes
1. Characteristics that distinguish
prokaryotic and eukaryotic cells
Types of prokaryotic cells
• Archaea: thermophiles: halophils,
thermophils (strain 121), acidophils,
methanogens :CO2 and H2→CH4)
• Domain bacteria or eubacteria
• Cynobacteria:PS and reduced N2 to NH3
• Use DNA sequence to study the species
diversity (5000/millions species, 415
species in month)
Types of eukaryotic cells: cell
specialization
Differentiation
Six model organisms
The sizes of cells and their
components
The human perspective
The prospect for cell replacement
therapy
1.4 Viruses
virion (outside the living cell)
Viroids (RNA only, potato virus)
Experimental pathways
The origin of eukaryotic cells
•Prokaryotic cells: 2.7 billion years old
•Eukaryotic cells: ~1.7 billion years
•Both share similar genetic codes,
enzymes, metabolic pathways, and
plasma membrane
•Common ancestor
Evolutionary relationships:
compared nucleic acid sequence
Chloroplast rRNA,
16S rRNA from cyanobacteria,
18S rRNA from eukaryotic ribosome
rRNAs change very slowly over long periods
of evolutionary time
Three Domains of Life
Bacteria, Archaea, Eucarya
Gerald Karp
Cell and Molecular Biology
Fifth Edition
Chapter 2
CHAPTER 2 Part 1
The Chemical Basis of Life
Copyright © 2008 by John Wiley & Sons, Inc.
Chemical reaction
Protein interaction, DNA
replication, cell division
Muscle movement: move a few
molecules
Transport the molecules and
ions across the cell membrane
DNA
2.1 Covalent bonds
An atom is most stable when its
outmost electron shell is filled.
If two electron pairs are shared in
molecular oxygen (O2), the
covalent bond is a double bond.
The electronegativity of an atom
depends on two factors:
1. the number of positive
charges in its nucleus (the more
protons, the more
electronegative)
2. the distance of the outer
electrons from the nucleus ( the
greater the distance, the less
electronegative)
1. Polar and nonpolar molecules
Unsymmetrical distribution of
electrons
2. Ionization
2.2 Noncovalent bonds (1-5
kcal/mol)
do not depend share electrons and
goverened by a variety of weaker linkages,
mediate dynamic interactions among
molecules in the cells
1. ionic bonds
2. hydrogen bonds
3. hydrophobic interaction
4. van der Waals forces
• 1. ionic bonds
2. hydrogen bonds
3. hydrophobic interaction
4. van der Waals forces
• 1. ionic bonds
2. hydrogen bonds
3. hydrophobic interaction
4. van der Waals forces
• 1. ionic bonds
2. hydrogen bonds
3. hydrophobic interaction
4. van der Waals forces
• 1. ionic bonds
2. hydrogen bonds
3. hydrophobic interaction
4. van der Waals forces
The life-supporting properties of water
2.1 covalent bond
2.2 non-covalent bond
2.3 Acids and Base
2.4 The nature of biological
molecules
• The chemistry of life centers around
the chemistry of the carbon molecules
• Back bones
2.6 four types of biological molecules
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Carbohydrates
Lipids
Proteins
Nucleic acids
Stereoisomerism
glyceraldehyde
2.6 four types of biological molecules
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Carbohydrates
Lipids
Proteins
Nucleic acids
lipids
1. Fats
2. Steroids
3. phospholipids
The phospohlipid
phosphatidylcholine
2.6 Four types of biological molecules
• Carbohydrates
• Lipids
• Proteins (10000 proteins in the cell, 450
amino acids in average polypeptide
chain, titin contains 30,000 amino acids)
• Nucleic acids
The structure of proteins
• Primary structure
• Secondary structure
• Tertiary structure
Protein domains
Dynamic changes within proteins
• Quaternary
The structure of proteins
• Primary structure (insulin aa sequence in
1950s)
rapid DNA sequencing can deduce the aa
sequence, but problems existed)
• Tertiary structure
• Protein domains
• Secondary structure
Dynamic changes within proteins
• Quaternary
Posttranslational modifications
• Alterations of 20 basic amino acids
(PTMs) to form other aa
(Add p group for regulation of cell to become a
normal or a cancer cell)
• Molecular interactions
• Shortening the life spin
The structure of proteins
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Primary structure
Secondary structure
Tertiary structure
Protein domains
Dynamic changes within proteins
Quaternary
The structure of proteins
• Primary structure
• Secondary structure
• Tertiary structure (conformation of total
protein,stabalized by non-covalent bond)
• Protein domains
• Dynamic changes within proteins
• Quaternary
Types of noncovalent bonds maintaining the conformation of proteins
Spatial distinct modules fold
independently: domains and have
different functions (bind to DNA or other
proteins)
(How could it happen? One protein
should only have one function?)
Fusion genes
• Dynamic changes within proteins
• NMR: study the dynamic structure
• Shift of H-bonds, movement of side chain,
and full rotation of aromatic rings of
tyrosine and phe
• Important in protein function
The structure of proteins
• Primary structure
• Secondary structure
• Tertiary structure (conformation of total
protein,stabalized by non-covalent bond)
• Protein domains
• Dynamic changes within proteins
• Quaternary (more than one chain,
hydrophobic pitch connect each other)
Protein folding
The human perspective
• Molecular chaperones (helper proteins)
help unfolded or misfolded proteins to
achieve their proper 3-D conformations
• The role of molecular chaperons
(helper proteins) :
to prevent from interacting
nonselectively with other molecules in
the croweded compartments of the cell.
The emerging field of proteomics
• 30,000 genes from genomics study
• Proteomics (proteome): organisms,
particular tissue, cell, or cellular organelle
• Study large numbers of proteins in a single
experiment
• High speed computer and biochemistry
• More difficult to work with than DNA
(different protein has different character,
PCR for DNA, but proteins can not)
• Specific activity in vitro?
• Function in cell replication or locomotion?
• 3D structure? Appear in which cell during
development? And when?
• Localization?
• Modificationj?
• How much and how long? Protein
interaction?
• Diseases?
Protein function
• Protein microarrays (chips)
• Microscopic-sized spots on glass
microscope slide, each containing a
protein sample
• PSA, PSA antibodies
• Apply to other tests
Protein engineering
• Find a protein which can bind surface of AIDS
viral particle and remove it from the blood
• Computer predicts the shape of such protein
•Protein’s primary structure and tertiary structure must
know
•Folding problems
• Site-directd mutagenesis
1. Isolate an individual gene from human
chromosome
2. Alter its information content precisely
and synthesize the modified protein
3. thrombin (procoagulant and
anticoagulant)
Structure-based drug design
• Drug companies search new drugs from plants,
fungi, micro-organisms or chemically synthesized.
• Binding affinity with diseased proteins
• Aspirin: anti-inflammatory due to inhibit
cyclooxygenase-2 (synthesize prostagladins to
promote inflammation, pain, and fever)
• Prolonged using COX-2 can inhibit COX-1 and
damage the lining of the stomach.
• Isoleucine at position 523 in COX-1, a valine in COX2
• Design a drug that bind COX-2 much greater affinity
than COX-1
• COX-2 inhibitor: celebrex, vioxx
Protein adaptation and evolution
The structure of proteins
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Primary structure
Secondary structure
Tertiary structure
Protein domains
Dynamic changes within proteins
Quaternary