1-100 Lect Handouts
1-100 Lect Handouts
Course Outline
Atom Molecules Cell Structures Cells
Cell Functions
Propagation/Heredity
Expression Regulation
Cell Communication
Applied Cell Biology
Course Objective
Understand the molecular logic of the “living state”
How a molecule’s function arises from its structure,
How this information is conveyed to the rest of the cellular machinery
System Manipulation
CELL BIOLOGY
Composition of Matter
Composition of Matter
Atomic Structure
Composition of Matter
Carbon Atom
Composition of Matter
Electronegativity
The tendency of an atom to attract electrons towards itself.
Composition of Matter
Polarity of H2O
Results in Hydrogen Bonding
Composition of Matter
Ionic Bond
CELL BIOLOGY
Molecules of Life
Molecules of Life
Composition of Life
Molecules of Life
Building Blocks of Life
Molecules of Life
Polymers & Monomers
Macromolecules are polymers of smaller monomers molecules
Condensation reactions: Monomers join H2O Removal
Hydrolysis reactions: Use water to break polymers into monomers.
Molecules of Life
Condensation & Hydrolysis
CELL BIOLOGY
Proteins: Polymers of Amino Acids
Proteins: Polymers of Amino Acids
Protein Functions
The side chains or R groups give different properties to each of the amino acids
Proteins: Structure
Secondary Structure
α helices (hydrogen bonds between amino acid residues)
Proteins: Structure
Secondary Structure
Proteins: Structure
Tertiary Structure
Generated by bending and folding of the polypeptide chain
Proteins: Structure
Quaternary structure
Arrangement of multiple folded protein molecules in a multi-subunit complex.
CELL BIOLOGY
Protein Interactions
Protein Interactions
Weak interactions
3D structure
Protein Interactions
Protein: Denaturation
Heat, pH change: Tertiary and secondary structure as well as biological function.
CELL BIOLOGY
Sugar Polymers
Carbohydrates
Sugar Polymers
They act as source of energy that can be transported
They also have structural role
Monosaccharides
Disaccharides
Oligosaccharides (3-20)
Polysaccharides
Carbohydrates
Monosaccharides
Produced by plants, all living cells have glucose
CELL BIOLOGY
Glycosidic linkages
Carbohydrates
Glycosidic linkages
Disaccharide α or β orientation
Glycosidic linkages
Cellulose & Glycogen
Glycosidic linkages
Cellulose & Starch
CELL BIOLOGY
Lipids: Nonpolar Hydrocarbons
Week Bonds
Hydrophobic molecules
Water insoluble
Aggregate together (by hydrophobic and Van der Waals force)
Phospholipids
Amphiphatic Molecule
P-lipids: Aqueous Environment
The Bilayer
Two molecules thick head groups directed outward, The tails are packed together in the
interior of the bilayer.
Lipids: Cholesterol
Vitamins & Signals
Nucleic Acids
Nucleic Acids
DNA & RNA
Nucleic Acids
The Bases
Nucleic Acids
Prime Ends (3’& 5’)
Nucleic Acids
RNA vs. DNA
Nucleic Acids
DNA Uniform Width
Information in Sequence not Shape
Chicken vs. Egg: What Came 1st
Protein or DNA
Genetic information codes for enzymes
RNAs can achieve chemical catalysis, like enzymes: ribosome the active site is composed
entirely of RNA (peptide bond formation)
RNA: Information in Sequence and Shape
Why Then DNA?
CELL BIOLOGY
Unit of Life
Unit of Life
Cell Structure
Cellular compartments
Organelles
Structure & Function
Unit of Life
CELL BIOLOGY
Size Matters
Size Matters
Cell Structure
Cells are small to maintain large surface area to volume ratio
Prokaryotic Cells
No membrane enclosed internal compartments.
Plasma membrane regulates traffic (barrier).
Nucleoid region contains DNA.
Most have cell wall.
Prokaryotic Cells
Special Features
Cyanobacteria Chlorophyll containing have folds of plasma membrane, other have
mesosomes (energy).
Some have actin like filaments and other have Flagella made-up of Flagellin.
The Nucleus
Nuclear EMs
The Nucleus
Chromatin
Euchromatin
Hetrochromatin
Chromosome
CELL BIOLOGY
Ribosome
Ribosome
Protein & RNA
Free or attached to ER involved in protein synthesis.
Mitochondria & Chloroplasts.
Ribosome
CELL BIOLOGY
The Endoplasmic Reticulum
The Endoplasmic Reticulum
RER + SER
The Endoplasmic Reticulum
RER
Segregates newly synthesized Proteins
Glycogen hydrolysis
Secreting cells have abundant SER
CELL BIOLOGY
Golgi & Lysosomes
Golgi
Golgi Apparatus
Receives materials from the rough ER and modifies them.
Concentrates sorts and packages proteins and sends them to other destinations.
Manufactures poly-saccharides for the plant wall
Golgi
Lysosomes
Garbage Disposal
Contain many digestive enzymes.
Lysosomes
Lysosomes
CELL BIOLOGY
Mitochondria
Mitochondria
Make ATP Breakdown fuel
Mitochondria
Make ATP Breakdown fuel
Some protists have one, liver more than a thousan and egg a few hundred thousand MT.
Mitochondria and chloroplasts contain their own DNA and ribosomes for making some of
their own proteins
Mitochondria
Endosymbiosis
Mutual benefits permitted this symbiotic relationship
Photosynthesis
Detoxification of O2
CELL BIOLOGY
Cytoskeleton
Cytoskeleton
Shape & Function
Cytoskeleton
Cytoskeleton
Actin
Actin (cortical) Stabilizes cell shape.
Generates movement local.
Muscle contraction.
Constriction ring in cell divission (Cytokinesis). Cytoplasmic strreaming.
Cytoskeleton
CELL BIOLOGY
Cytoskeleton 2
Cytoskeleton
IF
IF stabilize cell structure (hold organelles).
Stabilize and maintain tissue rigidity (desmosomes).
Lamins in nucleus.
Resist tention.
Cytoskeleton
IF
Cytoskeleton
Microtubules
Rigid internal skeleton resist compression.
Tracks along for motor proteins.
Tubulin is a dimer of
α-tubulin and β-tubulin.
The two ends different plus (+) end & minus (–) end (cat Tail & dynamic).
Cytoskeleton
Microtubules 13
Cytoskeleton
Centrosome
CELL BIOLOGY
Motor Proteins
Motor Proteins
Dynein & Kinesin
Cargo & Motor Domain
Motor Proteins
Cilia and Flagella
ECM
Holds cells in tissues.
Physical properties of tissues cartilage, skin.
Orients cell movements during development/injury
Chemical signaling from one cell to another.
CELL BIOLOGY
The Miracle Workers
Energy Conversions & Enzymes
The Miracle Workers
One of biggest miracles of life is that it can perform slow reactions and the ones requiring
extreme conditions, quickly and at physiological conditions
CELL BIOLOGY
Energy
Energy
Capacity to do work
Potential energy is the energy of state or position; it includes the energy stored in chemical
bonds.
Kinetic energy is the energy of motion (and related forms such as electric energy, light, and
heat).
Energy Conversions
Efficiency Not 100%
H = G + TS
G = H – TS
CELL BIOLOGY
Free Energy (ΔG)
Free Energy (ΔG)
The Second Law
total energy =
usable energy + unusable energy
H = G + TS
G = H – TS
Changes in free energy, total energy, and entropy are related by the equation.
ΔG = ΔH – TΔS
ΔG of Combustion
Reactants Products
CH4 + 2O2 CO2 + 2H2O
H = G + TS H = G + TS 500 = 400 + 100 200 = 100 + 100
Reactants Products
G = H – TS G = H – TS
400 = 500 - 100 100 = 200 - 100
H2O adjacent to hydrophobic molecule are restricted to form hydrogen bonds with other water
molecules.
In living systems magnitude and sign of ΔG can depend significantly on changes in entropy
ΔS
ΔS = +ve in hydrolysis
CELL BIOLOGY
Exergonic & Endergonic Reactions
Exergonic & Endergonic Reactions
ΔG +ve or -ve
Endergonic reactions take up free energy and have a positive ΔG.
Reversible Reactions
Equilibrium
A B
∆G
Reversible Reactions
Equilibrium
The change in free energy (ΔG) of a reaction determines its point of chemical equilibrium,
For exergonic reactions, the equilibrium point lies toward completion (the conversion of all
reactants into products).
Reversible Reactions
Equilibrium
CELL BIOLOGY
ATP Hydrolysis
ATP Hydrolysis
Energy Currency
ATP Hydrolysis
Coupling
ATP Hydrolysis
Coupling
Speed of a Reaction
∆G Independent
CELL BIOLOGY
Enzymes
Biological Catalysts
Enzymes
Activation Energy
Activation Energy
Enzymes
CELL BIOLOGY
Enzymes Mechanisms
Enzymes Specificity
Enzymes Lower the Energy Barrier
Ea
How do Enzymes Work
Induced Fit
Conformational Change
Induced Fit
Conformational Change
CELL BIOLOGY
Enzyme Helpers
Enzyme Helpers
Enzyme Helpers
Enzyme Helpers
CELL BIOLOGY
Enzyme Regulation
Substrate Concentration
Enzyme Regulation
The Inhibitors
Enzyme Regulation
Irreversible inhibitors
Enzyme Regulation
Reversible inhibitors
Enzyme Regulation
The Citric Acid Cycle
Enzyme Regulation
Noncompetitive inhibiters
Physical Factors
Influence Enzymes
Cell Biology
Membranes
Membranes
More Than Barriers
Membranes Components
Membranes
Free Energy Dictates
Membranes
Features
Phospholipids coexist with water form a bilayer
Vital physiological roles: cell cell & cell interaction with environmental
Physical integrity: lipids, create a barrier to hydrophilic materials such as water and ions
Cell Biology
Membranes Components
Membranes Components
Fluid Mosaic Model
Each membrane has a set of proteins suitable to the specialized function of the cell or
organelle it surrounds.
Phospholipid molecule flip overs seldom (polar part of molecule hardly ever moves through
the hydrophobic interior
Molecular Movement
Lipid Rafts
Some proteins migrate freely others “anchored” to specific semisolid region different lipid
composition (very long fatty acid chains)
Cell Biology
Recognition & Adhesion
Recognition & Adhesion
Epithelial Cell Adhesion
Transport
Cell Biology
Transport Across Membrane
Osmosis: Passive Process
Channel Proteins
Active Transport
Cell Biology
Vesicle Formation
Vesicle Formation
Packaging Steps
The Proof
Cell Biology
Cell Division
Cell Division
Life Span & Continuity
All living organisms have a limited life span.
The essence of life is to propagate.
Cells are the basic unit of life.
Cell division is the basic process that ensures the continuity of life.
Cell Division
The Necessity
Unicellular organisms propagate by splitting into two cells.
Multicellular organisms: replace damaged or senescent cells.
Billions of cells die each day in humans, (blood epithelia)
Cell Division
Cell Biology
Cell Cycle
Cell Division
Cell Cycle
Cyclins & CDK
RB
Cell Biology
Chromosome
Chromosome
Chromosome
Centrosome
Cell Biology
Chromosome
Chromosome
Chromosome
Centrosome
Cell Biology
Meiosis I
Cell Biology
Karyotype
Meiosis I
Meiosis I
Crossing Over
Cell Biology
Meiosis II
Meiosis II
Meiosis II
Meiosis
Features
Reduces chromosome number from diploid to
haploid
Ensures each of the haploid products has a complete set of chromosomes
Promotes genetic diversity among the products.
Cell Biology
The Comparison
The Comparison
The Comparison
The Common Mistake
Cell Biology
Genetics Introduction
Genetics
Historic Background
Blending VS Particulate
Genetics
Definitions
A character is an observable feature, such as flower color.
Cell Biology
The Question
The Question
The Anatomy of the Subject
The Question
The Technique
The Question
The Question
The Answer
Cell Biology
The Lessons Learned
Mendel’s Model of Inheritance
ss trait not expressed in the F1 generation, (reappeared in F2) Mendal concluded SS trait
domin-ant to the ss trait (recessive).
Mendel worked with his data mathematically & concluded each pea plant has two units of
inheritance for each character, 1 from each parent.
During gamete production only 1 of these paired units is given to a gamete. Resulting
zygote contains 2, (produced fusion of 2 gametes).
The Lessons Learned
Mendel’s unit of inheritance is now called a gene. Different forms of a gene (S & s) are
called alleles.
Homozygous have two copies of the same allele (ss). Heterozygous have two different alleles
of the gene in question (in this case, Ss).
The physical appearance of an organism is its phenotype. Phenotype to be the result of the
genotype, or genetic constitution.
Genetics
The Punnett Square
Cell Biology
The First Law
The Law of Segregation
When any individual produces gametes, the two alleles separate, so that each gamete
receives only one member of the pair of alleles.
Other Traits Also Obey
The Test Cross
Cell Biology
The Second Law
The Second Law
Probabilities
If an event is absolutely certain to happen, its probability is 1.
If it cannot possibly happen, its probability is 0. Otherwise, its probability lies between 0
and 1.
The Second Law
Independent Assortment
Alleles of different genes assort independently of one another during gamete formation.
That is, the segregation of the alleles of gene A is independent of the segregation of alleles of
gene B.
The Second Law
Cell Biology
Aberrant Phenomenon
Incomplete Dominance
Heterozygotes show a phenotype intermediate between those of the two homozygotes
Codominance
Both alleles appear in heterozygotes
Epistasis
Effect of one gene dependent on the presence of one or more 'modifier genes'
Cell Biology
Linkage & Recombination
Linkage
Independent Assortment
Linkage
No Independent Assortment
The Actual Picture
The Actual Picture
Cell Biology
Genetics Map
Linkage
No Independent Assortment
Genetic Map
Recombination Frequencies
Recombination Frequencies
Cell Biology
Clinical Genetics I
Clinical Genetics
Pedigree Symbols
Pedigree
What Is My Mode of Inheritance
Autosomal Dominant Disorders
Manifested in the heterozygous state
At least one parent of an index case is affected
Both males and females transmit the condition
When an effected person marries an unaffected child has one chance in two of having the
disease
Reduce Penetrance: Some individuals inherit the mutant allele but are phenoltypically
normal
Variable Expressivity: gene expression is variable e.g. neurofibromatosis type 1 range from
brown spots to multiple tumors and skeletal deformities
Age of on set can delayed e.g. Huntington
Cell Biology
Clinical Genetics II
Autosomal Recessive Disorders
Manifested in the homozygous state
Parents usually not affected but the siblings may show the trait 1/4 (25%)
Affected individual may be product of consanguineous marriage (low frequency alleles)
The expression of the defect more uniform
Mostly enzyme proteins affected (half of normal enzymes ensures margin of safety)
Hereditary Molecules
Dr. Fridoon Jawad Ahmad
Hereditary Molecules
Dr. Fridoon Jawad Ahmad
Antiparellel
A=T
G=C
DNA Function From Structure
Store an enormous
amount of information and could account for species and individual differences
Expression of a phenotype
Cell Biology
Replication Models
Replication Models
The Meselson-Stahl Experiment
Replication Models
Cell Biology
DNA Replication The Molecular View
The Molecular View
The Molecular View
The Replication Model
Cell Biology
DNA Replication The Process
The Golden Rule
Requirements
1) The Original
2) The Machinery
5) Energy
4) Initiator
2) The Machinery
5) Energy
4) Initiator
Genetic Engineering
Uses Of Cloned DNA
Genetic Engineering
Human Health
Cell Biology
RFLP
RFLP
RFLP
RFLP
Restriction Fragment
Length polymorphisms (RFLP)
Can reveal mutations in DNA which may indicative of disease
Gel Electrophoresis
Cut Gel Pic
Cell Biology
DNA Transfer
Transferring DNA to a Membrane
Probing DNA
Probing DNA
Cell Biology
Genetic Information is Converted into Protein
Archibald Garrod 1908
Alkaptonuria (“black urine”)
Beadle Tatum 1940s
Neurospora
Beadle Tatum 1940s
Neurospora
Beadle Tatum 1940s
Beadle Tatum 1940s
Beadle Tatum 1940s
Cell Biology
The Dogma
The Dogma
Info flows from DNA to RNA to proteins
Crick Hypotheses
Overview
The Viral Exceptions
Cell Biology
Transcription
Transcription Initiation
Transcription Elongation
Transcription Termination
Transcription
Cell Biology
Genetic Code
Genetic Code
Genetic Code
Deciphering the Genetic Code
The Adapter
T-RNA Structure
tRNA Structure
Cell Biology
Charging tRNA
Aminoacyl-tRNA Synthetase
Charging
Benzer Experiment
Charging
Charging
Cell Biology
Translation Workbench
Translation Workbench
Translation Workbench
Translation Workbench
Translation Workbench
Cell Biology
Translation
Initiation Complex
Initiation Complex
Elongation
Elongation
Termination
Animation
Termination
Cell Biology
Protein Targeting
Prokaryotes
Eukaryotes Protein Targeting
Eukaryotes Protein Targeting
Eukaryotes Protein Targeting
Eukaryotes Protein Targeting
Cell Biology
Mutations
Mutations
Point mutations
Point mutations
Sickle Allele
Point mutations
Point mutations
Mutations
Cell Biology
Transcription Regulation
in E. Coli
E. Coli Transcription Regulation
Inducible System
Inducible System
The trp Operon
The trp Operon
Transcription Regulation
E. Coli Transcription Regulation
Cell Biology
Transcription Regulation
in E. Coli
E. Coli Transcription Regulation
Inducible System
Inducible System
The trp Operon
The trp Operon
Transcription Regulation
E. Coli Transcription Regulation
Cell Biology
Transcription Regulation
In Eukaryotes
Eukaryote Transcription Regulation
Eukaryote Transcription Regulation
DNA Organization
DNA Reorganization
DNA Reorganization
DNA Reorganization
Cell Biology
Eukaryotic Transcription
Eukaryotic Transcription
Eukaryotic Transcription
Eukaryotic Transcription
Eukaryotic Transcription
Transcribing Multiple Genes
Eukaryotic Transcription
Cell Biology
RNA Processing
RNA Processing
Introns Removed
Evidence Introns Removed
RNA Processing
RNA Processing
X Chromosome Inactivation
X Chromosome Inactivation
Cell Biology
Cell Signaling & Prehistoric world
Cell Signaling
Cell Signaling
Cell Signaling
Cell Biology
The Instructions & The Design
The Instructions
Design
Transcription Regulation
Expression of One Gene
Cell Biology
The Modes & Principles
The Modes