Mid Term #1
Study Guide 1
Lecture 1 What is Science
• Empirical Science
– Observational, descriptive
Science
– Detecting patterns, or
departures from patterns
• Theoretical Science
– Generating and testing models
(hypothesis testing)
– Concerned with explaining
observations and making
predictions
• Technological Science
– Generating new methods and
processes
– Troubleshooting
Basic Assumptions/ Beliefs
• Materialism and Naturalism
1. Operate in a closed system
2. Nothing interferes with the
system
3. All events are totally
dependent on the whole
system
4. Natural explanation for all
phenomena
• Scientific Knowledge is
based on methodology
–
–
–
–
Observation
Hypothesis
Experimentation
Dynamic, not static
Scientific Reasoning
(Propositional Logic)
Inductive Logic
• Reasoning from Experiences
• Knowledge Expanding
– Contains more information
than premise
Deductive Logic
• Start with general knowledge
and predict a specific
observation
• Truth preserving
– Contains less information than
premises
Key Terms
• Postulate
• Premise
• Principle
• Theory
• Hypothesis
• Test
• Principles of Inductivism
• The number of
observations forming the
basis of a generalization
must be large
• Observations must be
repeated under a variety of
conditions
• No observations should
conflict with universal laws,
principles, or theories
Recognize an example of inductive
reasoning
Problems with Inductivism
• Appeals to logic
• Appeals to experience
• How many observations are
required?
• What constitutes significant
variation
• Must retreat to probability
• Theory: dependent on inductivism
• Inductivism fails to throw new light
on science
Deduction
Process
1. Statement of problem
2. Hypothesis as to the
cause of the problem
3. Experimental tests for
each hypothesis
4. Predict results (how to
accept or reject the
hypothesis
5. Observe results
6. Draw conclusions from
the results (accept or
reject the hypothesis)
Premis
•Fundamental Assumptions
•Must be both valid and true
Good tests
•Prediction is logically deducible
•Prediction is improbable
•Prediction is verifiable
Deductive Process
Class is too large
Problem
If I make this confusing, then some
students will drop
Test
Deliver miserable
Lecture about logic
Accept
Reject
Hypothesis
Some people will get confused
and drop
Prediction
Observation?
Observation
Conclusion
No Drops
Loads-O-Drops
Reject
Accept
Was This a Good Example?
Deduction
Premis, Fundamental Assumptions
Must be both valid and true
Good tests
Prediction is logically deducible
Prediction is improbable
Prediction is verifiable
Hypothetico-Deductive Method
Laws and
theories
Induction
Facts
acquired
through
observation
Deduction
Predictions
and
explanations
Deductive Falsification
(Conjectures and Refutations)
• Positivist– Only has supporting
evidence
– Ignores evidence
against
The Process of Popperian
Falsification
Falsification science:
•The process of developing a set
of hypotheses, tentatively
proposed, to as accurately as
possible describe an aspect of the
natural world.
Hypotheses must be falsifiable:
•One develops logically possible
observations which, if established,
would falsify the H0.
Problems with Falsification:
• Complexity of any realistic test
of most modern theories is often
extremely difficult.
•Theory underlying hypotesis may
be false.
•The premise behind hypothesis
is false.
Example of Falsification from Induction
•Many lectures on the philosophy of science are boring
•This is a lecture on the philosophy of science
•Therefore, this class is boring
What is the experiment that would falsify or disprove our hypothesis?
Objectivism vs. Subjectivism
Role of the Scientist
Understanding whether science and
scientists are objective or subjective
is important in understanding what
science is. These are not models but
definitions of how science is
practiced.
Science Values
Scientific Knowledge is not good or
bad…Its Goodness or Badness
depends on how it’s used and by
what standard you grade it.
Is science and are scientists
objective?
•Subjectivism holds that man is
not objective, but subjected to his
surroundings, training, personal
experience, etc.
•Objectivism is the belief that
mankind can be removed from or
independent of his surroundings
and experiences while making
observations.
Objectivism and Subjectivism result in at
least three concurrent views of science
1- Scientific
Imperialism
•Science is the Truth
Arbiter
•Therefore,
anything goes if
scientists say so
•2- Postmodern
3- Godisms
Relativism
Mankind is created and
ultimately Truth is God
•Plurality of Truths
Science is only one form Revealed.
Science is a product
of Subjective Truth
of mankind, therefore
•Science has made
science must be
errors in the past,
carefully evaluated
Therefore, science
for its potential good
and scientists
and/or bad outcomes.
Objectivism is the belief
that a scientist can be
should be:
removed from or
•Questioned,
independent of his
Evaluated and
surroundings and
Regulated
experiences while making
observations, conclusions Subjectivism holds that science
and scientists are not objective,
and recommendations.
but antecedents to surroundings,
training, personal experience,
etc.
Since truth is ultimately
Revealed and science is
error prone, science is
subjective and an ethical
society must take care to
evaluate and judge science’s
pursuits and products
carefully.
Science: Research programs
•
•
Hard core theory, often not
easily challenged
Generates lots of Hypotheses
Progress
Degenerate
Problems: 1) Politically influenced, 2) Special interest influenced, 3) Dictate large
expenditures of public funds, 4) Redirect or sometimes misdirect science thrusts
and 5) Often ideologically driven or oriented.
Examples: Genomics, NASA, Aids Research, Cancer Research, Human Genome Project, etc.
Kuhn’s Scientific Revolution
Normal Science
A Scientific Theory is
likea pitcher of water.
Crisis
Revolution
Prescience
Scientific knowledge is dynamic and changes
with new discoveries and additions of new
information
When one Theory fails its
components often flow into
another Theory.
Lecture 1: What is Science wrap-up
• Human endeavor dependent on the scientific
community and society.
• Not infallible, often guided by scientific fads,
yet the best we have.
• There are at least 4 ways of describing
Science: Inductivism, Falsification, Science
Programs & Kuhnian Revolutions.
• Based on presuppositions about how the
world is, & many if not all, of these
presuppositions are not scientifically
testable.
Lecture 2: Outline
• What is life
–
–
–
–
Characteristics- DefinitionProperties- Dynamic changing
Components- building blocks
Minimal life- simplest life forms
• Organizing Life
– Taxonomy
• Functions of Life
– Metabolism
• Plant
• Animal
• Carbon, nitrogen and water cycling
• Origin of Life
– Where did it come from
• Current Models
• Introduction to Biological Chemistry
What Is Life
Properties of Life
• Dynamic = changing
• Adaptability
• Contain Information (DNA)
• Ordered Structure
• Uniformity of class
Definition of Life
• An organismic state characterized by the
capacity for metabolism, growth, reaction to
stimuli, and reproduction.
• A principle or force that underlies the distinctive
quality of animate beings.
• The quality that distinguishes a vital and
functional organism from inanimate objects.
Characteristics of Death
• Absence of life
• Total and permanent cessation of all vital
(living) function
• Absence of the characteristics of life
Key Terms in “Life” Definition
• Metabolism
– Acquires and expends “energy”
• Growth
– Makes what it needs
• Reaction
– Senses Environment
• Reproduction
– A population of one and only one is going to
run into trouble sooner than later
Smallest Components of Life
• Elements (atoms)
• Molecules
• Macromolecules
– Information carriers
• Enzymes, proteins
– Functional capacity
• Membranes and walls
– Boundaries, and containers
Categories of life’s components
Atoms, Amino Acids,
Macromolecules, Organelles,
Cells, Cells, Organ, Systems,
Symbiotic organisms, Individual,
Populations
Life Quantitatively
Complexity
– High
– Low
How Biologists Measure Size: Metrics
Assignment: Learn the metric measuring system and life sizes
How simple can life be?
Phytoplasma and Mycoplasma = simplest cell, lack a cell wall,
DNA for 200 functions (walking pneumonia, STD’s)
Not Cells
•Virus = RNA or DNA wrapped in protein coat (HIV,
poliomyellitis)
• Viroid = Tightly wound DNA or RNA (coconut cadang cadang,
bunchy top)
• Prions = 1/100 to 1/1000 the size of a virus, composed of
proteins (Scapies, Multiple Sclerosis, Lou Gehrig’s disease)
Is each of these really alive?
Are they independent?
Can they reproduce or metabolize
on their own?
Pneumonia mycoplasma
HIV
Organizing Life
Classification
Systematics
Taxonomy
Cladistics
Phylogenics
•
Methods of Classification
– Based on some relevant
distinguishing characteristic
– It should be meaningful
– It should not be arbitrary
•
Basis of Classifications
– Morphological characteristics
• Types of structures,
Size, Diet, Reproduction
– Molecular characteristics
•
•
•
•
•
•
•
Kingdom
Phylum
Class
Order
Family
Genus
Species
Classification
The Kingdoms
• Animalia- multicelluar, consumers
• Plantae- multicellular, producers
• Fungi- mostly decomposers
• Protista- One-celled, producers and consumers
• Eubacteria- Normal, true bacteria, consumers…
• Archaebacteria- Extreme bacteria, consumers…
• Mitochondrial DNA
• Nuclear DNA
Basic Premis (assumption) of
taxonomy “Natura non facit saltum”
(Nature does not make leaps).
So Who’s Related
Classification schemes generate different
trees based on which sorting criteria is
used.
Trees based on physical characteristics
or reproductive characteristics are often
different from trees made from
comparisons of DNA. The specific DNA
used also generates different trees.
Mitochondrial DNA, or different nuclear
genes encoding common proteins can
each generate different trees.
DNA sequences provide a direct
record of the genealogy of extant
species. surprising changes have
recently been proposed for The
tree of mammalian orders. These
range from grouping whales with
hippos, to placing African golden
moles closer to elephants than to
their fellow insectivores.
Molecules remodel the mammalian tree
Wilfried W. de JongTrends in Ecology & Evolution 1998,
13:270-275
Functions of Life
Four categories for organizing the characteristic of life:
Metabolism, Growth, Reaction, Reproduction
Metabolism
•Storing and releasing energy
•Converting light energy into
chemical energy
•Plants fix carbon from the air
•Animals release carbon from
storage moleclues
Growth
•Using the stored energy
•Incorporating acquired materials
Catabolic processes- breaking
down
Anabolic processes- building up
Reaction
• Sensing environment
– Receptors andMetabolic
changes
• Reacting to changing
environment
Examples from Bacteria,
Plants and Animals
• Reacting to internal
environment: Homeostasis
Reproduction
• Sexual Reproduction: Cell
Process: Meiosis and Mixing
Genes
• Replication, Division: Cell
Process: Mitosis and High
fidelity copies
• Adaptation and Selection
Where does life come from?
Objectivism and Subjectivism result in different views of
science. These views and their assumptions affect
fundamental questions of science
Three Models
•
•
•
Neo-Darwinian
– Macro Evolutionary Process
Cosmic Inoculation
– Panspermia
Divine Creation
The Standard Story
The Big Bang
•
12-15 billion years ago all matter was
compressed into a space the size of our sun
•
Sudden instantaneous distribution of matter
and energy throughout the known universe
Planet Formation
– About 4.6 and 4.5 billion years ago
The Earth formed and conditions were just
right
The right kinds of molecules formed
The right molecules assembled
•
•
•
•
Is Life is a property of matter and
energy?
Abiogenesis Origin (Neo-Darwinian)
Macro Evolutionary Process
Chance, Necessity, and Self Organization
Chemical processes generated life
precursors
Precursors assembled into proto cells
Extraterrestrial deposition (Panspermia)
Organisms came from somewhere else
Chemistry came from somewhere else
Presuppositions
Do Presuppositions Matter?
–
–
–
•
Naturalism and Materialism
Life is a property of matter and energy
Chance, Necessity, and Self Organization
Of course it works, we’re here aren’t we?
Origin of Life
Its life Jim, but
not as we know it
Where did it come from?
New ideas, new questions
Matter, Energy, and Information
Where does the information come
from?
Normal Science
Crisis
Revolution
Prescience
Summary
Definitions
Characteristics
Life and Energy
Forms of Simple Life
Identifying Life
Does Life Exist Elsewhere in the
Universe?
• Are terrestrial biochemistry and
molecular biology the only
such phenomena that can
support life?
• With only one example, we
don’t know which properties of
Properties
life are general and necessary,
Organization
and which are the result of
Measuring Life
specific circumstances or
Origin of Life
historical accident.
Lecture 3: Chemistry of Life
Chemical Bonds
Elements
• Fundamental forms of matter
• Can’t be broken apart by normal means
Most Common Elements in Living Organisms:
Oxygen, Hydrogen, Carbon, and Nitrogen
What Are Atoms?
• Smallest particles that retain properties of an element
• Made up of subatomic particles:
– Protons (+)
– Electrons (-)
– Neutrons (no charge)
Atomic Number
Atomic Mass
Isotopes and Radioisotopes
Uses of Radioisotopes
Tracers, Imaging, Radiation therapy
HYDROGEN
What Determines Whether
Atoms Will Interact?
Electrons
• Carry a negative charge
• Repel one another
• Are attracted to protons in the
nucleus
• Move in orbitals - volumes of
space that surround the
nucleus
Electron Vacancies
• Unfilled shells make atoms
likely to react
• Hydrogen, carbon, oxygen,
and nitrogen all have
vacancies in their outer shells
Chemical Bonds, Molecules,
& Compounds
• Bond is union between
electron structures of atoms
• Atoms bond to form molecules
• Molecules may contain atoms
of only one element - O2
• Molecules of compounds
contain more than one element
- H 2O
Chemical Bonds
1. Ionic
Bonding
•One atom loses electrons
and becomes a positively
charged ion
•Another atom gains an
electron and becomes a
negatively charged ion
Electrostatic
Covalent
Ion Formation
Atom has equal number of electrons and
protons - no net charge
Atom loses electron(s), becomes positively
charged ion
Atom gains electron(s), becomes negatively
charged ion
SODIUM
ATOM
11 p+
11 e-
electron transfer
CHLORINE
ATOM
17 p+
17 e-
•Charge difference attracts
the two ions to each other
SODIUM
ION
11 p+
10 e-
CHLORINE
ION
17 p+
18 e-
Electrostatic
Covalent
Chemical Bonds
2. Covalent
Bonding
•Atoms share a pair or
pairs of electrons to fill
outermost shell
•High energy bonds hold
together tightly.
•Require high levels of
energy to break covalent
bonds
Two Flavors of
Covalent Bonds
Non-polar Covalent
•
•
•
Atoms share electrons equally
Nuclei of atoms have same number of
protons
Example: Hydrogen gas (H-H)
Polar Covalent
•
•
•
Number of protons in nuclei of
participating atoms is NOT equal
Molecule held together by polar
covalent bonds has no NET charge
Electrons spend more time near
nucleus with most protons
–
–
Example: Water
Electrons more attracted to O nucleus
than to H nuclei
KEEP YOUR EYE ON THE ELECTRONS
Example
+
slight negative charge at this end
O
H
H
molecule has
no net charge
( + and - balance
each other)
slight positive charge at this end
Hydrogen Bonding
A bond by Hydrogen between two atoms
• Important for O and N
• Lets two electronegative atoms interact
– The H gives one a net + and the other one
that is still – is attracted to it.
• The H proton becomes “naked” because
its electron gets pulled away.
Hydrogen bond figure
KEEP YOUR EYE ON THE ELECTRONS
Like Charge Atoms Repel Each Other
-
-
-
+
-
Opposite Charge Atoms Attract Each Other
Hydrogen bonds are the most
physiologically relevant chemical bond
in all of nature!!!!
Hydrogen bonds hold DNA
strands together and allow
them to come apart and
reform!
Hydrogen bonds take
place between different
parts of a polypeptide
chain and give the
molecule the glue it needs
to fold correctly
one
large
molecule
another
large
molecule
a large
molecule
twisted
back
on
itself
Water
Properties of Water
• Polarity
• Temperature-Stabilizing
• Cohesive
• Solvent
• Molecule has no net charge
Water Is a Polar
Covalent Molecule
• Oxygen end has a slight
negative charge
• Hydrogen end has a slight
positive charge
Hydrophilic & Hydrophobic
• Hydrophilic substances
– Polar
– Hydrogen bond with water
– Example: sugar
•
Hydrophobic substances
– Nonpolar
– Repelled by water
– Example: oil
Water Is a Good Solvent
• Ions and polar molecules dissolve
easily in water
• When solute dissolves, water
molecules cluster around its ions or
molecules and keep them separated
• Solvent- polar
– Keeps ions in solution
– Doesn’t dissolve membranes
The pH Scale and pH in general
Measures H+ concentration of fluid
Change of 1 on scale means 10X
change in H+ concentration
Highest H+
Lowest
+
H
0---------------------7-------------------14
Acidic
Neutral
Basic
Hydrogen Ions: H+
Unbound protons
Have important biological effects
Form when water ionizes
Acids
Donate H+ when dissolved in water
Acidic solutions have pH < 7
Strong acids forcefully give up H+
Bases
Accept H+ when dissolved in water
Acidic solutions have pH > 7
Strong bases forcefully take H+
The problem with water is a static view
H3O+ ↔H2O↔OHDraino and battery acid
are really bad for your
skin. Understanding pH,
the basis of protein
structure and formation
of peptide bonds help
you to understand why
Organic Compounds
Carbon’s Bonding Behavior
• Outer shell of carbon has 4 electrons;
can hold 8
• Each carbon atom can form covalent
bonds with up to four atoms
• Carbon atoms can form chains or
rings
• Other atoms project from the carbon
backbone
Functional Groups
• Atoms or clusters of atoms that are
covalently bonded to carbon
backbone
• Give organic compounds their
different properties
Examples of Functional Groups
Hydroxyl group - OH
Amino group
- NH3+
Carboxyl group - COOHPhosphate group - PO3Sulfhydryl group - SH
Hydrogen and other
elements covalently
bonded to carbon:
Carbohydrates, Lipids,
Proteins, Nucleic Acids
Types of Reactions
Functional group transfer, Electron
transfer, Rearrangement,
Condensation, Cleavage
Condensation Reactions
• Form polymers from subunits
• Enzymes remove -OH from one
molecule, H from another, form
bond between two molecules
• Discarded atoms can join to form
water
Hydrolysis
• A type of cleavage reaction
• Breaks polymers into smaller units
• Enzymes split molecules into two
or more parts
• An -OH group and an H atom
derived from water are attached at
exposed sites
THE MACRO MOLECULES
Carbohydrates
Monosaccharides
(simple sugars)
Oligosaccharides
(short-chain carbohydrates)
Polysaccharides
(complex carbohydrates)
Monosaccharides
•
•
•
Simplest carbohydrates
Most are sweet tasting, water soluble
Most have 5- or 6-carbon backbone
Glucose (6 C) Fructose (6 C)
Ribose (5 C) Deoxyribose (5 C)
Polysaccharides
•
•
Straight or branched chains of many sugar
monomers
Most common are composed entirely of
glucose
– Cellulose
– Starch (such as amylose)
– Glycogen
Cellulose & Starch
• Differ in bonding patterns between
monomers
• Cellulose - tough, indigestible,
structural material in plants
• Starch - easily digested, storage
form in plants
Glycogen
• Sugar storage form in animals
• Large stores in muscle and liver
cells
• When blood sugar decreases, liver
cells degrade glycogen, release
glucose
Chitin
• Polysaccharide
• Nitrogen-containing groups
attached to glucose monomers
• Structural material for hard parts of
invertebrates, cell walls of many
fungi
glucose
fructose
+ H 2O
sucrose
glucose
fructose
THE MACRO MOLECULES
Lipids
• Most include fatty acids
– Fats
– Phospholipids
– Waxes
• Sterols and their derivatives
have no fatty acids
• Tend to be insoluble in water
Fatty acid(s)
Fatty Acids
• Carboxyl group (-COOH) at
one end
• Carbon backbone (up to 36 C
atoms)
– Saturated - Single bonds
between carbons
– Unsaturated - One or more
double bonds
stearic acid oleic acid
Triglycerides
linolenic acid
Phospholipids
• Main components of cell
membranes
Sterols and Derivatives
• No fatty acids
• Rigid backbone of four
fused-together carbon
rings
• Cholesterol - most
common type in
animals
Waxes
• Long-chain fatty acids linked to
long chain alcohols or carbon rings
• Firm consistency, repel water
• Important in water-proofing
THE MACRO MOLECULES
Amino Acids
Properties of Amino Acids
• Determined by the “R group”
• Amino acids may be:
– Non-polar
– Uncharged, polar
– Positively charged, polar
– Negatively charged, polar
Protein Synthesis
• Protein is a chain of amino acids
linked by peptide bonds
• Peptide bond
– Type of covalent bond
– Links amino group of one
amino acid with carboxyl
group of next
– Forms through condensation
reaction
THE MACRO MOLECULES
Protein
Protein Shapes
•
•
Fibrous proteins
– Polypeptide chains arranged as strands
or sheets
Globular proteins
– Polypeptide chains folded into
compact, rounded shapes
Protein Structure
•
•
•
•
Primary- just the sequence (1D)
Secondary- interactions on the chain
(2D)
Tertiary- interactions between parts of
the chain the chain. (3D)
Quaternary- interactions with other
chains
Primary Structure & Protein Shape
•
•
Sequence of amino acids
Primary structure influences shape in two
main ways:
– Allows hydrogen bonds to form
between different amino acids along
length of chain
– Puts R groups in positions that allow
them to interact
Secondary Structure
• Hydrogen bonds form between different
parts of polypeptide chain
• These bonds give rise to coiled or
extended pattern
• Helix or pleated sheet
Tertiary Structure
• Folding as a result
of interactions between R groups
• The 3D structure of a protein
Quaternary Structure
• Some proteins are made up of more
than one polypeptide chain
• Structure of a protein when it is folded
with other polypeptides
Polypeptides With Attached Organic
Compounds
• Lipoproteins
– Proteins combined with cholesterol,
triglycerides, phospholipids
• Glycoproteins
– Proteins combined with
oligosaccharides
Examples of Secondary
Structure
heme group
coiled and twisted polypeptide
chain of one globin molecule
Hemoglobin
Denaturation
• Disruption of three-dimensional shape
• Breakage of weak bonds
• Causes of denaturation:
– pH
– Temperature
• Destroying protein shape disrupts
function
A Permanent Wave
hair’s
cuticle
one hair cell
bridges
broken
keratin
macrofibril
hair wrapped
around cuticles
coiled keratin
polypeptide
chain
microfibril (three
chains coiled
into one strand)
different
bridges
form
A brief survey of a
some protein types
•
•
•
•
•
•
•
•
Structural
Muscle
Binding
Signaling
Storage protein
Defensive protein
Transportation
Enzymes
Structural
Function:
Hold together
Give shape
Examples:
Hair
Tendons
Ligaments
Structural
Function:
Attachment
Collagen
molecule
Collagen
A triple helix
Microfibril
Polypeptid
e chain
Collagenous
fiber
Macrofibril
Structural Proteins
Actin
Crystallins
Keratin
Lens Fibers
Muscle
Function: Contraction
Muscle
Flagella
Image courtesy of Dr. Fatih
Uckun, Parker Hughes Institute,
St. Paul, MN
Movement in the Cell
Actin and Myosin V
ATP Dependent Reaction
Nature Reviews Molecular Cell Biology 2, 387-392 (2001)
Signaling
Function:
Messengers
Receptors
Insulin
Storage
Function:
Store What?
Expensive molecules for later use
Chemical energy
Ovalbuminglobular glycoprotein
Protein for Defense
• Example: Antibodies
• Key component of immune system
• Label invading microbes as intruders
Transportation
Function:
Moving molecules:
In side the organism
Between cells
Inside Cells
Example: Getting O2 to
where it’s needed
Hemoglobin: gives
blood cells their red
color…
Concepts in Transportation
The Basic Terms
• Permeability
• Diffusion - Gradients
• Membrane transport
– Active
– Passive
– Bulk
Cell Membranes And
Selective Permeability
(Think Grapefruit!)
O2, CO2, H2O,and
small non-polar
molecules
Sugar, and other large,
polar molecules
+, Na+,
ions
such
as
H
I
CI-, Ca++
X
Gradients- Unequal distributions
Membranes are required for gradients
Mechanisms of
Crossing Over
(the membrane)
1.
2.
3.
4.
Diffusion across lipid bilayer
Passive transport
Active transport
Bulk Transport
Endocytosis
Exocytosis
Transport Proteins
•
•
•
•
Span the lipid bilayer
Interior is able to open to both sides
Change shape when they interact with solute
Play roles in active and passive transport
Active Transport
• Movement of target is against
the concentration gradient
(Think about Water flowing up hill)
• Transport protein requires
energy
(Not free, someone pays)
• ATP is often the source of
chemical energy
Passive Transport
• Going down the gradient
(That whole water runs down hill thing)
• Selective- only some things fit
• Not directional- two way door
• Its FREE! Does not require any
energy input
Bulk Transport
Exocytosis
Endocytosis
Features of Enzymes
Enzymes make, break and
rearrange chemical bonds
Enzymes make unlikely
reactions happen
and happen faster
Enzymes aren’t usually
reactants or
products and usually
aren’t used up or
severely altered
The same enzyme usually
works for both the
forward and reverse
reactions
Each type of enzyme
recognizes and binds to
only certain molecules.
(Substrate Specificity)
Activation Energy
• For a reaction to
occur, an energy
barrier must be
surmounted
• Enzymes make
the energy barrier
smaller
activation energy
without enzyme
starting
substance
activation energy
with enzyme
energy
released
by the
reaction
products
two
substrate
molecules
substrates
contacting
active site
of enzyme
active sight
TRANSITION
STATE
(tightest
binding but
least stable)
end
product
enzyme
unchanged
by the
reaction
Induced-Fit Model
• Substrate molecules
are brought together
• Substrates are oriented
in ways that favor
reaction
• Active sites may
promote acid-base
reactions
• Active sites may shut
out water
Pulling it all together
Receptor
Inhibitor
Metabolic pathway
Enzyme
Hydrophobic and Hydrophillic
Sterols
Transport protein
Why is Cholesterol
Important?
Sales of Lipitor grew 25% in
2001 to $4.4 billion. Pfizer
spent $50 million on Lipitor
ads last year.
Observational studies provide
overwhelming evidence that
HDL-C is an independent risk
factor for coronary heart
disease
High cholesterol
doesn’t care who
you are
Basic Cholesterol Metabolism
• We make all the cholesterol we need and it is absolutely
essential
• Major sources of circulating cholesterol
– Peripheral cholesterol synthesis
– Hepatic cholesterol synthesis
– Intestinal cholesterol absorption
• Once synthesized or absorbed it is packaged into
lipoprotein complex so that it can be transported
• The problem is getting cholesterol back to the liver
– High Density Lipoprotein
– Low Density Lipoprotein
• Transport through the cell membrane is receptor mediated
Basic Cholesterol Metabolism
• Delivery of cholesterol from other tissues to the
liver results in the formation of Low Density
Lipoprotein (LDL) complexes.
• Problem: Big and sticky and form plaques on
artery walls
– Atherosclerosis- Clogged arteries
• when plaques break loose the plug up arteries
HDL = Good
LDL or VLDL = Bad
Cholesterol and Health
What effects your cholesterol level?
•
•
•
•
•
Diet
Exercise
Genetics
Age
Pharmaceuticals
Statins
• Originally intended to be antibiotics
– Bacteria need cholesterol too
– Found a small molecule in a Penicillum
• Mechanism of Action
– Bind a receptor that is just on liver cells
– Once inside, get stuck in an enzyme’s active site.
Compete with substrate
– HMG-CoA Reductase
– Liver cells want more cholesterol to package so
they make more receptors for LDL
• Less synthesis and more adsorption results in
lower cholesterol levels.
Statins
What is a good drug anyway?
1. Good enzyme inhibitor- a little bit goes a long
way (IC50)
2. Specific tissue action- only works where you
want it
3. Pharmacokinetics- goes in fast and stays there
a long time.
4. Doesn’t interact with other drugs
Cholesterol
Synthesis
Metabolic Pathway
• Linear, branched or
cyclic?
• What else do we
need HMG-CoA
Reductase for?
• Does it only affect
liver cells?
Statins on the Market
•
•
•
•
Atorvastatin, Lipitor, Pfizer
Fluvastatin, Lescol, Novartis
Lovastatin, Mevacor, Merck
Prevastatin, Pravachol, Bristol-Myers
Squibb
• Simvastatin, Zocor, Merck
• Cerivastatin, Baycol, Bayer
•The more polar the drug is,
the less likely it will be
absorbed by non target cells
(non-liver)
•More negative side affects
are associated with the less
polar (more hydrophobic
compounds)
Lipophilic=Lipid loving=Hydrophobic
How Good It Works
POLAR!
Too Much of a
Good Thing
Rhabdomyolysis
•Rapid muscle tissue
breakdown. (Quite painful, like a
permanent cramp)
•Heme protein-induced renal
tubular cytotoxicity,
intraluminal cast formation,
leading to tubular obstruction
(kidney plugs up and you can’t
make urine, very bad)
Lecture 3: Chemistry of Life
Part 3 of 2
Goals:
• Finish with biochemistry
• Understand: 1.)What protein is, 2.)What protein
does, and 3.) how make one
• Relate concepts of protein structure and
function to real events and issues
Key Terms: Amino acid, R-group, polypeptide, protein types,
protein structure, peptide bond, lipoprotein, glycoprotein,
Assingment:
For Tuesday, read Ch 12 and 13
For Thursday, read Ch 8 and 14
Lecture 5: Nucleic Acids into
Protein. (Ch 12 and 13)
Goals
– Introduction to nucleic acids, DNA and
replication
– Understand how to make a protein
(transcription)
Key Terms: DNA, RNA, nucleic acid, replication,
topoisomerase, DNA polymerase, ligase, RNA
polymerase, transcription, translation, ribosome,
splicing, mRNA, tRNA, initiation, elongation,
termination, genetic code, mutations,
Hershey Chase
Experiment
• Label protein or DNA with radio
isotopes
• Infect bacteria with phage
particles
• Sheer off the phage (blender)
• Separate bacteria and phage
protein
• Progeny of the phage
Conclusions:
DNA is the infective material
not protein
Strong inference: DNA is
genetic information
Viral Infection:
Viral DNA infects bacteria
Viral DNA codes for viral
proteins
Viral proteins assemble to
form new viral particles
virus particle
labeled with 35S
virus particle
labeled with 32P
Hershey Chase Expt.
bacterial cell (cutaway view)
label
outside cell
label inside cell
DNA Structure
Nucleotide Bases (4)
Adenine pairs with Thymine
Guanine pairs with Cytosine
Structure and function Relationship
•DNA is two nucleotide strands held together by hydrogen
bonds
•Hydrogen bonds between two strands are easily broken
•Each single strand then serves as template for new strand
Making DNA (polymerization) requires energy
•Energy for strand assembly is provided by removal of two
phosphate groups from free nucleotides.
•ATP, CTP, TTP, GTP, all have high energy chemical bonds
that can be broken and used to do work. (Reference ATP and
chemical energy)
Covalent
Bonds
DNA Repair
•Mistakes can occur during replication
•DNA polymerase can read correct sequence from
complementary strand and, together with DNA ligase, can
repair mistakes in incorrect strand
•The other context of repair
–Environmental factors damage DNA too
–How is DNA repaired after it has been made?
Hydrogen
Bonds
DNA Replication Summary
Enzymes
• Topoisomerase unwinds strands
• DNA Polymerase attaches new complementary
nucleotides
• DNA Ligase connects the bonds between phosphate
sugar backbone of the new nucleotides
Chemical Bonds
• Break hydrogen bonds with Topoisomerase
• Make Hydrogen bonds with DNA Polymerase
• Make covalent bonds with DNA Ligase
Final Products
• The strand being replicated is the template
• Start with one copy of a DNA molecule and end with two
copies
– New copies have one new strand and one old strand
– Both copies are “identical” to the original
Nucleic Acids Into Proteins
DNA
Same two steps produce ALL proteins:
1.DNA is transcribed into RNA
–Occurs in the nucleus
–Gene promoter is the start stop switch
–The promoter determines the start site
–RNA is spliced(introns removed, exons kept)
–mRNA moves into cytoplasm
2.mRNA is translated into polypeptide
chains by ribosomes
–Translation occurs in three steps
• Initiation at the start codon
• Elongation of the polypeptide chain
• Termination at the stop codon
–Proteins are folded polypeptide chains.
Promoter
• A base sequence in the DNA that signals
where transcription starts
• For transcription to occur, RNA polymerase
must first bind to a promoter
• The promoter is the on and off switch for a
gene
Base Pairs
Are Different
RNA
DNA vs. RNA
Ribonucleic Acid
•
•
•
•
Bases are G,A,C, & U
Uracil (U) pairs with adenine (A)
Contains 2 ° information
Does other things
Catalytic, Inhibitor…
Deoxyribonucleic Acid
•
•
•
Bases are G,A,C, & T
Thymine pairs with adenine
Contains 1° information
Transcription & DNA Replication
•
Like DNA replication
•
RNA polymerase catalyzes nucleotide
addition
Product is a single strand of RNA
•
–
–
–
Nucleotides added in 5’ to 3’ direction
Unlike DNA replication
Only small stretch is template
Uricil Base (U)
Thymine Base (T)
Sugar is
Different
Nucleic Acids Into Proteins
Three Classes of RNAs
1.Messenger RNA (mRNA)-Carries
protein-building instruction
2.Ribosomal RNA (rRNA)-Major
component of ribosome
3.Transfer RNA (tRNA)-Delivers amino
acids to ribosome
Initiation
•
•
•
Initiator tRNA binds to small ribosomal
subunit
Small subunit/tRNA complex attaches to
mRNA and moves along it to an AUG
“start” codon
Large ribosomal subunit joins complex
Elongation
Key Players in Translation
• Ribosome- Center of action
• The tRNAs
• Start Codon (Met)
• The tRNAs- big cast
• The mRNA- translated script
•
•
•
mRNA passes through ribosomal subunits
tRNAs deliver amino acids to the
ribosomal binding site in the order
specified by the mRNA
Peptide bonds form between the amino
acids and the polypeptide chain grows
• Stop codon
Termination
mRNA
•
• Message RNA is a copy of some DNA
• The mRNA is used as a template for
making proteins
• DNA is never used as a template for
proteins!
•
•
•
A stop codon in the mRNA moves onto
the ribosomal binding site
No tRNA has a corresponding anticodon
for the stop codon
Proteins called release factors bind to the
ribosome
mRNA and polypeptide are released
Gene Transcription
Transcribed
DNA winds up
again
mRNA
transcript
5’
3’
DNA to be
transcribed unwinds
RNA polymerase
Growing RNA
transcript
3’
5’
Direction of
transcription
Transcript Modification
unit of transcription in a DNA strand
3’
exon
intron
exon
transcription
intron
5’
exon
into pre-mRNA
poly-A
tail
3’
cap
5’
snipped
out
snipped
out
5’
3’
mature mRNA transcript
Genetic Code
• Set of 64 base triplets
– 4 bases, 3 positions
– Ie. 4 x 4 x 4 = 64
• Twenty kinds of amino
acids are specified by 61
codons
• Codon
• Most amino acids can be
– Sets of nucleotide bases
specified by more than one
read in blocks of three
codon
• 61 specify amino acids
• 3 stop translation
– Stop Codons
• Example: Six codons
specify leucine
– UUA, UUG, CUU, CUC, CUA,
CUG
codon in mRNA
Binding site for mRNA
tRNA Structure
A (second
binding site
for tRNA)
P (first
binding site
for tRNA)
Elongation
anticodon
in tRNA
amino
acid
tRNA molecule’s
attachment site
for amino acid
OH
Polysome
• A cluster of many ribosomes translating
one mRNA transcript
• Transcript threads through the multiple
ribosomes like the thread of bead
necklace
• Allows rapid synthesis of proteins
What Happens to the
New Polypeptides?
• Some just enter the cytoplasm
• Many enter the endoplasmic reticulum and
move through the cell membrane system
where they are modified
Don’t Worry About it Till After Test #1 !
Overview
Transcription
mRNA
Mature mRNA
transcripts
rRNA
ribosomal
subunits
tRNA
mature
tRNA
Translation
TRANSLATION
CLIP
SUMMARY
CLIP
When
Things
Go
Wrong
Mutations:
original
base triplet
in a DNA
strand
Base-Pair Substitutions
Insertions
Deletions
Frameshift Mutations
•
•
•
•
Insertion-Extra base added into
gene region
Deletion-Base removed from
gene region
Both shift the reading frame
Result in many wrong amino
acids
Effect of Mutations
on DNA vs. RNA?
a base
substitution
within the
triplet (red)
As DNA is replicated, proofreading
enzymes detect the mistake and
make a substitution for it:
POSSIBLE OUTCOMES:
OR
One DNA molecule
carries the original,
unmutated sequence
The other DNA
molecule carries
a gene mutation
mRNA
PARENTAL DNA
amino acid sequence
ARGININE
GLYCINE
TYROSINE
TRYPTOPHAN
ASPARAGINE
ARGININE
GLYCINE
LEUCINE
LEUCINE
GLUTAMATE
altered mRNA
BASE INSERTION
altered amino acid sequence
Mutation Rates
• How often do mutations happen
– Cell type
– Gene type
• Only mutations in germ (sex) cells are
be passed to the next generation
• Mutations in somatic cells stay in the
body they happen in
Genetic Diseases and Cancers
Lecture 6: Diabetes, sugar, and
ATP
Objectives
Understand how sugar metabolism works
Understand how to make ATP
Understand where sugar comes from
Understand how sugar metabolism affects you
Key Terms
metabolism, gradient, equilibrium, phosphorylation, ATP, ADP
electron transport, glycolysis, insulin, glycogen, glucagon
NEXT WEEK:
Cell Division and Cancer
Leading Causes of Deaths
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Heart Disease: 700,142
Cancer: 553,768
Stroke: 163,538
Lung diseases: 123,013
Accidents (unintentional injuries): 101,537
Diabetes: 71,372
Influenza/ Pneumonia: 62,034
Alzheimer's disease: 53,852
Kidney Disease: 39,480
Septicemia (infection): 32,238
(Most current data available are for U.S. in 2001) www.cdc.gov/nchs/fastats/lcod.htm
I don’t have to worry about
that stuff till I get old!
All races, both sexes, 20–24 years
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Accidents (unintentional injuries)
Assault (homicide)
Intentional self-harm (suicide)
Cancer
Heart disease
Genetic abnormalities
Human immunodeficiency virus (HIV)
Stroke
Influenza and pneumonia
Diabetes
Relative to the
national population
of 20-24’s, are MSU
students less likely to
die from the top 3?
It’s difficult for one to
prevent bad luck, or
being a victim?
Two Types of Diabetes
Type 1
• Juvenile diabetes
• Autoimmune
disease
– Beta cells in
pancreas are killed
by defense
responses
• Treated with
insulin injections
Type 2
• Adults affected
• Insulin sensing
system impaired.
• Beta cells stop making
insulin.
– Pancreas burns out
• Treated with diet,
drugs
Diabetes Mellitis
• Cells in muscles, liver and fat don’t use
insulin properly
• Disease in which excess glucose
accumulates in blood, then urine
• Signs and Symptoms
–
–
–
–
–
–
Excessive urination
Constant thirst and or hunger
Fatigue
Weight loss
Blurred vision
Sores that don’t heal
Risk Factors
•
•
•
•
•
•
•
•
Age
Overweight
Inactive (exercise > 3x/week)
Family history: African, American Indian,
Asian, Pacific Islander, Hispanic or Latino
descent.
Siblings or parents have diabetes
Gestational diabetes
Blood pressure over 140/90
HDL (good) cholesterol is low and
triglicerides are high
Reducing Risks
• Physical activity- 30 min 5 days/week
• Diet Modification
– Low fat- 25% of calories max
– Low alcohol
• Maintain Reasonable body mass
– No crash diets
– Modify dietary intake
Control of Glucose Metabolism
insulin
Glucose is
absorbed
Glucose
uptake
Glucose to
glycogen
Glucose falls
Krispy
Kreme
Donuts (12)
Cells use
glucose
Glucose rises
Glycogen to
glucose
glucagon
Energy from Macromolecules
•
•
•
•
Carbohydrate
Glycogen
Protein
Lipids (fat)
Absorption Mechanisms
•Food is broken down to macro molecules
•Macro molecules are disassembled by
enzymes in the intestines
•Actively transported across membrane:
–Monosaccharides
–Amino acids
•Nutrients diffuse from gut cells into blood
stream
bile salts
bile salts
+
carbohydrates
proteins
EPITHELIAL
CELL
INTERNAL
ENVIRONMENT
FAT
GLOBULES EMULSIFICATION
DROPLETS
MICELLES
CHYLOMICRONS
Energy from Macromolecules
Energy Reserves
•
•
•
Glycogen is about 1 % of the body’s
energy reserve
Proteins is 21% of energy reserve
Fat makes up the bulk of reserves (78 %)
Carbohydrate Breakdown and Storage
•
•
•
•
•
Glucose is absorbed into blood
Pancreas releases insulin
Insulin stimulates glucose uptake by cells
Cells convert glucose to glucose-6phosphate
–
Phosphate, functional group,
phosphorylation
This traps glucose in cytoplasm where it
can be used for glycolysis
Making Glycogen
•
If glucose intake is high, ATP-making
machinery goes into high gear
•
When ATP levels rise high enough,
glucose-6-phosphate is diverted into
glycogen synthesis (mainly in liver
and muscle)
•
Glycogen is the main storage
polysaccharide in animals
Using Glycogen
• When blood levels of glucose decline,
pancreas releases glucagon
• Glucagon stimulates liver cells to convert
glycogen back to glucose and to release it
to the blood
• (Muscle cells do not release their stored
glycogen. This is their stored sugar!)
Key Concepts
Glucose Storage
1. Glucose is used to make ATP first
2. When ATP store is full, glucose is stored
3. Glycogen is a big branched polymer of
stored glucose
– Glycogen isn’t very soluble so it is
trapped inside the cell where it is
stored.
Energy from Macromolecules
Energy from Proteins
• Proteins are broken down to
amino acids and the amino acids
are broken down
• Amino group is removed,
ammonia forms, is converted to
urea and excreted
• Carbon backbones can enter the
Krebs cycle or its preparatory
reactions
Key Concept: Proteins can be used to
make ATP in Krebs Cycle
Energy from Fats (lipids)
•
•
•
•
Most stored fats are triglycerides
Triglycerides are broken down to
glycerol and fatty acids
Fatty acids are broken down and
converted to two carbon blocks that
enter the Krebs cycle (acetyl CoA)
Key Concept: Fatty acids are used to
make ATP
.Conversion is slow, 2C’s at a time
Before it can even enter Krebs Cycle
Key Concept: Contraction as well as
many other cellular processes require
lots of energy
• Muscle cells require huge amounts of
ATP energy to power contraction
• The cells have only a very small store of
ATP
• There are three pathways muscle cells
use to get ATP
ATP Is Universal Energy Source
• Photosynthesizers get energy from the
sun
Animals get energy second- or third-hand
from plants or other organisms
Regardless, the energy is converted to the
chemical bond energy of ATP
Making ATP
• Plants make ATP during photosynthesis
• Cells of all organisms make ATP by
breaking down carbohydrates, fats, and
protein
Two Main Pathways for
making ATP
Anaerobic pathways
FAST
• Don’t require oxygen
• Start with glycolysis in cytoplasm
• Completed in cytoplasm
Aerobic pathways
SLOW
• Require oxygen
• Start with glycolysis in cytoplasm
• Completed in mitochondria
(Note: special membrane and
gradient)
Overview of Aerobic Respiration
CYTOPLASM
glucose
ATP
GLYCOLYSIS
energy input to
start reactions
e- + H+
(2 ATP net)
2 pyruvate
2 NADH
MITOCHONDRION
2 NADH
8 NADH
2 FADH2
e-
e- + H+
2
CO2
e- + H+
KREBS
CYCLE
e- + H+
ELECTRON
TRANSPORT
PHOSPHORYLATION
H+
4
CO2
2
32
ATP
ATP
water
e- + oxygen
TYPICAL ENERGY YIELD: 36 ATP
Main Pathways Start with Glycolysis
Efficiency of Aerobic Respiration
•
•
•
•
686 kcal of energy are released
•
7.5 kcal are conserved in each ATP
•
When 36 ATP form, 270 kcal (36 X 7.5) are
captured in ATP
•
Efficiency is 270 / 686 X 100 = 39 percent
•
Key Concept: Most energy is lost
as heat
Glycolysis occurs in cytoplasm
Reactions are catalyzed by enzymes
Glucose
2 Pyruvate
(six carbons)
(three carbons)
Overview of Aerobic Respiration
C6H1206 + 6O2
6CO2 + 6H20
glucose
carbon
oxygen
water
dioxide
Summary of Energy Harvest (per molecule of
glucose)
•
Glycolysis
– 2 ATP formed by substrate-level
phosphorylation
•
Krebs cycle and preparatory reactions
– 2 ATP formed by substrate-level
phosphorylation
•
Electron transport phosphorylation
– 32 ATP formed
Overview of Aerobic Respiration
CYTOPLASM
glucose
ATP
GLYCOLYSIS
energy input to
start reactions
e- + H+
(2 ATP net)
2 pyruvate
2 NADH
MITOCHONDRION
2 NADH
8 NADH
2 FADH2
e-
e- + H+
2
CO2
e- + H+
KREBS
CYCLE
e- + H+
ELECTRON
TRANSPORT
PHOSPHORYLATION
H+
4
CO2
2
32
ATP
ATP
water
e- + oxygen
TYPICAL ENERGY YIELD: 36 ATP
Aerobic Respiration
electron transport chain over simplified
Key concept: If you pull water apart, it
really wants to get back together again
• By giving the Oxygen atom in water an
electron, it will give you a proton, which is
actually a H+
• Oxygen is the final electron acceptor?
How it Works:
1.Pull a hydrogen off a water (HOH to OH-)
2.Pull the hydrogen (H+) across a membrane
(electrochemical GRADIENT)
3.Make the H+ do work on its way back to
OH-
Coenzyme Production
Key Concepts: Coenzyme production
1.Kreb’s cycle produces activated
coenzymes
2.Coenzymes push electron transport
Electron Transport
• Occurs in the mitochondria
• Coenzymes deliver electrons to
electron transport systems
• Electron transport sets up H+ ion
gradients
• Flow of H+ down gradients powers ATP
formation The final electron acceptor is
oxygen
Importance of Oxygen
• Electron transport phosphorylation
requires the presence of oxygen
• Oxygen withdraws spent electrons
from the electron transport system,
then combines with H+ to form water
http://www.sp.uconn.edu/~terry/images/anim/ETS.html
What’s the deal with Oxygen?
Fermentation Pathways
Anaerobic Pathways
•
•
•
•
•
•
Begin with glycolysis
Do not break glucose down completely
to carbon dioxide and water
Yield only the 2 ATP from glycolysis
Steps that follow glycolysis serve only
to regenerate NAD+
Yeasts
• Single-celled fungi
• Carry out alcoholic fermentation
• Saccharomyces cerevisiae
– Baker’s yeast
– Carbon dioxide makes bread
dough rise
• Saccharomyces ellipsoideus
– Used to make beer and wine
• MSU hard cider project:
Sacchromyces banyan DV10
•
Do not use oxygen
Produce less ATP than aerobic
pathways
Two types
– Fermentation pathways
• The burn
• The Buzz
– Anaerobic electron transport
Anaerobic Electron Transport
• Carried out by certain bacteria
• Electron transport system is in
bacterial plasma membrane
• Final electron acceptor is compound
from environment (such as nitrate),
NOT oxygen
– Doesn’t require Oxygen
– Can’t work with Oxygen
• ATP yield is low
• Lets bacteria live where other
organisms can’t
Lactate Fermentation
GLYCOLYSIS
C6H12O6
2
ATP
energy input
2 NAD+
2 ADP
2
4
NADH
ATP
energy output
2 pyruvate
2 ATP net
LACTATE
FORMATION
electrons, hydrogen
from NADH
2 lactate
GLYCOLYSIS
Alcoholic
Fermentation
C6H12O6
2
ATP
energy input
2 NAD+
2 ADP
2
4
NADH
ATP
2 pyruvate
energy output
2 ATP net
ETHANOL
FORMATION
2 H2O
2 CO2
Animals Can’t
do this!
2 acetaldehyde
electrons, hydrogen
from NADH
2 ethanol
Processes Are Linked
Aerobic Respiration
Photosynthesis
• Reactants
• Reactants
– Sugar
– Carbon dioxide
– Oxygen
– Water
• Products
• Products
– Carbon dioxide
– Sugar
– Water
– Oxygen
ATP Formation in Plants
• When water is split
during photolysis,
hydrogen ions are
released into thylakoid
compartment.
(Electrochemical
GRADIENT)
• More hydrogen ions are
pumped into the
thylakoid compartment
when the electron
transport system
operates
ATP Formation
• Electrical and H+
concentration gradient
exists between
thylakoid compartment
and stroma
• H+ flows down
gradients into stroma
through ATP synthesis
• Flow of ions drives
formation of ATP
Summary of Photosynthesis
light
12H2O
LIGHT-DEPENDENT
REACTIONS
2
ADP + ATP
Pi
6CO2
6O
NADP+ NADPH
PGA CALVIN- PGAL
BENSON
CYCLE
RuBP
P
C6H12O
6
(phosphorylated
glucose)
end product (e.g. sucrose, starch, cellulose)
Two Important
Pathways
Light Reaction
• Makes ATP from light
energy
Dark Reaction
• Makes glucose by
burning ATP
• Uses CO2 from the air
and water to make
glucose
Machinery of
Noncyclic Electron Flow
H2O
photolysis
e–
e–
NADP+
PHOTOSYSTEM II
PHOTOSYSTEM I
ATP SYNTHASE
NADPH
ADP
+ Pi
ATP
Lecture 7: Cell Division and Cancer
Objectives:
Understand basic concepts of cancer
Understand cell division
Understand how cell division is regulated
Understand programmed cell death
Key Terms: Mitosis, interphase, tumor, metastasis,
angiogenesis, neoplasm, benign, malignant, adenoma,
carcinoma, tumor suppressor, growth factor, check point,
oncogene, programmed cell death
Leading Causes of Death
Total US Population
•
Heart Disease
•
•
•
•
•
•
•
•
Stroke
Lung diseases
Accidents
Diabetes
Flu and Pneumonia
Alzheimer's disease
Kidney Disease
Infections
• Cancer
US Population 20-24
•
•
•
•
•
•
•
•
•
•
Accidents
Homicide
Suicide
Cancer
Heart disease
Genetic Disease
HIV (AIDS)
Stroke
Flu and Pneumonia
Diabetes
(Most current data available are for U.S. in 2001) www.cdc.gov/nchs/fastats/lcod.htm
Leading Sites of New Cancer
and Deaths 2003 estimates
Male
Prostate
Lung
Colon
Bladder
Melanoma
New cases
220,900
91,800
72,800
42,200
29,900
Female
Breast
Lung
Colon
Uterine
Ovary
Deaths
28,900
88,400
28,300
8,600
na
New cases
211,30039,800
80,100
74,700
40,100
24,400
Deaths
68,800
28,800
6,800
14,300
Cancer
Features of Cancer Cells
1. Make their own growth signals
2. Insensitive to growth stopping signals
3. Insensitive to self destruct signals
4. Immortal ! : unlimited replication
5. Stimulate new blood vessel growth
6. Invasive : move out of tumor
How does Cancer Start?
Cellular Damage Control
Normal cells protect their DNA
Information
Damage control system
1.Detect DNA and cellular damage
2.Stop cell division (prevent replication of
damage)
3.Activate damage repair systems
4.Activate self destruct system
DAMAGE
EVENT
Stop Cell Division
Activate Damage Repair
Damage Assessment
Repair
Fails
Damage Accumulation
Leads to Cancer
Severe
Damage
Mild to
Moderate
Damage
Programmed Cell Death
Repair is Successful
##
Tumor
• An abnormal mass of undifferentiated cells
• It often interferes with body functions
• It can absorb nutrients needed elsewhere
• It can be benign, grow slowly and stay in one
area.
• It can be malignant, grow rapidly and spread
to other parts of the body
Cancer Terminology
• Neoplasm-Cells that have no potential to spread to
and grow in another location in the body
• Benign-Non-cancerous growth that does not invade
nearby tissue or spread
• Malignant-growth no longer under normal growth
control
• Metastasis-spread of cancer from its original site to
another part of the body
• Adenoma-A benign tumor that develops from
glandular tissue
• Carcinoma-A tumor that develops from epithelial
cells, such as the inside of the cheek or the lining of
the intestine
Understanding Cancer
To understand cancer, you must understand
three fundamental cellular processes
1.Cell Division
2. Gene Regulation
3. Programmed Cell Death
Cell Division
Control of the Cycle
• Key concepts of Cell Division
•
1. Cell Cycle
2. DNA Replication
3. Chromosome Division
4. Cell Division
•
• There are two types of cell division
Mitosis – for growing, results in two
identical cells.
Meiosis – for sexual reproduction, results
in four cells with only one copy of
chromosomes
Cell Cycle
• Cycle starts when a new cell forms
• During cycle, cell increases in mass
and duplicates its chromosomes
• Cycle ends when the new cell divides
Key Terms: Cell Cycle, Chromosomes, Cell
Division
•
Once S begins, the cycle
automatically runs through G2 and
mitosis
The cycle has a built-in molecular
brake in G1 (p53 tumor
suppressor)
Cancer involves a loss of control
over the cycle, malfunction of the
“brakes”
Decoding the Cell Cycle
Interphase: Phase between division and starting division again.
Three intervals of Interphase
1. G1 1st Growth phase- cell makes parts, and does normal things
2. S Synthesis phase- DNA replication
3. G2 2nd Growth phase- making parts for cell division
4. G0 Zero Growth phase
•
•
Like getting stuck in park
Terminal development
Key Concept:
At each step, the cell must
be in order
Longest part of the cycle
Cell mass increases
Cytoplasmic components double
DNA is duplicated
G1
S
G2
Cell Division
Mitosis
Key Concept:
• During mitosis each cell gets a high
fidelity copy of each chromosome
• Multiple check points prevent runaway cycling
Cancer cells are in run-away mode,
the checkpoints are broken or
ignored
Stupmer?
also… Key Concept:
• Each chromosome has two
strands of DNA
• Each chromosome has one copy
of each gene*
• Each somatic cell has two of
each chromosome
• Each somatic cell has two copies
of each gene*
Chromosomes
DNA
DNA and proteins
arranged as cylindrical fiber
Chromosome: A double
stranded DNA molecule &
attached proteins
Nucleosome
Histone
Chromosome (unduplicated)
Almost no naked DNA
Chromosome (duplicated)
Gene Regulation
Oncogenes
Genes who’s products transform normal
cells into cancer cells.
– Required for normal cell cycling
– Products of these genes are no
longer regulated
– “gain of function”
Tumor suppressors
Proteins that prevent the progression of
the cell cycle
– P53 is a DNA binding protein that
recognizes damaged DNA and
stops DNA replication
– “loss of function”
Imortalization
• Normal cells only divide about 50
times in a petri dish (if you can get
them to divide)
• Cancer cells just keep dividing (HeLa
and MCF-7 cells)
• Telomers (ends of chromosomes)
usually spell the end for normal cells,
but they don’t wear out
Growth Factors
• Signaling molecules that enhance cell
division
• Activate “cascade” of signaling inside
cell
• Hyperactive cascade members can
trigger cell division by turning genes on
at the wrong time
• Hyperactivity lets cells ignore regulatory
signals
Anchorage dependent cell cycle arrest
• Adhesion is required for normal cell
division rates
• Cancer cells loose cell adhesion
molecules
• Cancer cells don’t respond to limiting
signals
Angiogenesis
• Blood vessel formation
• Cancer cells trick blood vessels into
supplying nutrients
• Cancer cells secrete the growth factors
that they are using
Gene Regulation
Gene Regulation
Cancer and Smoking
• The smoke from a cigarette contains about 1010 particles/ml
and 4800 chemical compounds
• There are over 60 carcinogens in cigarette smoke that
have been evaluated for which there is 'sufficient evidence for
carcinogenicity' in either laboratory animals or humans
• These compounds damage DNA in the cells of the lung.
The mechanism behind the damage is unknown.
• Damage leads to mutations
Smoking and Cancer
• The kicker
– Somehow p53 gets more mutations than other
randomly selected sites
– The mutations keep p53 from binding to DNA
– This means that p53 can no longer prevent DNA
replication when there is other damage
x
xx
STOP
DNA
mp53
p53
GO
Transcription
Translation
MUTANT
NORMAL
Programmed Cell Death
The cell death program
1. Activated by cell surface receptors
2. Makes pores in Mitochondria
3. DNA is chopped up
4. Blebbing (not popping)
5. Adsorption by neighbors
• Nematodes, frog tails,
webbed fingers, and HIV
Key Concepts
Cells are caused to die on purpose
Two examples: Epithelial cells, Damaged cells
Based on a balance of protecting proteins and killing proteins.
Cancer cells often have high levels of protecting proteins.
AKA: Apoptosis
Colon Cancer
• Crypt
• Polyp
• Malignant polyp
Colon Cancer Progression
“The Cancer has Spread”
Two linked processes
•
Metastasis
•
Angiogenesis
Key concept: Metastasized cancer cells require
angiogenesis to produce another malignant
tumor
•
Angiogenesis- formation of new blood
vessels
•
Metastasis- migration of cancer cells to a
new location
Metastasis
Cancer cells leave the tumor and establish new
colonies in other tissues
Angiogenesis
Depends on growth factors released by the
invading cancer cells
Markers for Cancer
•
•
•
•
Markers are proteins found in blood
Levels markers correlates with certain
cancer types
Some tumor markers are antigens,
others are enzymes.
Example: prostate-specific antigen
(PSA) is a marker for prostate cancer
in males
Angiogenesis
Angiogenesis and Metastasis
Cancer
Research
• Growing cells
in culture
allows
researchers to
investigate
processes and
test treatments
without danger
to patients
HeLa Cells
Henrietta Lacks
• Most cells
cannot be
grown in
culture