Mid Term

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Mid Term 1

• Study Guide 1

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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
• Operate in a closed system
• Nothing interferes with the system
• All events are totally dependent on the whole
  system
• Natural explanation for all phenomena
• Scientific Knowledge is based on methodology
• Observation
• Hypothesis
• Experimentation
• Dynamic, not static

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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

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• 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

• 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

Recognize an example of inductive reasoning
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Deduction

• Process
• Statement of problem
• Hypothesis as to the cause of the problem
• Experimental tests for each hypothesis
• Predict results (how to accept or reject the
  hypothesis
• Observe results
• 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

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Deductive Process
Class is too large
Problem
If I make this confusing, then some students will
drop
Hypothesis
Deliver miserable Lecture about logic
Test
Accept Reject
Some people will get confused and drop
Prediction
Observation?
Observation
No Drops
Loads-O-Drops
Conclusion
Accept
Reject
Was This a Good Example?
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Deduction

• Premis, Fundamental Assumptions
• Must be both valid and true
• Good tests
• Prediction is logically deducible
• Prediction is improbable
• Prediction is verifiable

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Hypothetico-Deductive Method
Laws and theories
Deduction
Induction
Facts acquired through observation
Predictions and explanations
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Deductive Falsification(Conjectures and
Refutations)

• Positivist-
• Only has supporting evidence
• Ignores evidence against

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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?

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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 badIts
  Goodness or Badness depends on how its 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.

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Objectivism and Subjectivism result in at least
three concurrent views of science

• 2- Postmodern Relativism
• Plurality of Truths
• Science is only one form of Subjective Truth
• Science has made errors in the past,
• Therefore, science and scientists should be
• Questioned, Evaluated and Regulated
• Subjectivism holds that science and scientists
  are not objective, but antecedents to
  surroundings, training, personal experience, etc.

• 1- Scientific Imperialism
• Science is the Truth Arbiter
• Therefore, anything goes if scientists say so
• Objectivism is the belief that a scientist can be
  removed from or independent of his surroundings
  and experiences while making observations,
  conclusions and recommendations.

3- Godisms Mankind is created and ultimately
Truth is God Revealed. Science is a product of
mankind, therefore science must be carefully
evaluated for its potential good and/or bad
outcomes. Since truth is ultimately Revealed and
science is error prone, science is subjective and
an ethical society must take care to evaluate and
judge sciences pursuits and products carefully.
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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.
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Kuhns Scientific Revolution
A Scientific Theory is likea pitcher of water.
Scientific knowledge is dynamic and changeswith
new discoveries and additions of newinformation
When one Theory fails its components often flow
into another Theory.
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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.

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Lecture 2 Outline

• What is life
• Characteristics- Definition-
• Properties- 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

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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

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• Categories of lifes 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
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How simple can life be?

• Phytoplasma and Mycoplasma simplest cell, lack
  a cell wall, DNA for 200 functions (walking
  pneumonia, STDs)
• 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 Gehrigs disease)

Is each of these really alive? Are they
independent? Can they reproduce or metabolize on
their own?
HIV
Pneumonia mycoplasma
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Organizing Life

• Classification
• 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

• 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
• Mitochondrial DNA
• Nuclear DNA

Basic Premis (assumption) of taxonomy Natura non
facit saltum (Nature does not make leaps).
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So Whos Related

• 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.

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.
Molecules remodel the mammalian tree Wilfried W.
de JongTrends in Ecology Evolution 1998,
13270-275
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Functions of Life Four categories for organizing
the characteristic of life Metabolism, Growth,
Reaction, Reproduction

• 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

• 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

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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, were here arent we?

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Origin of Life Where did it come from?
Its life Jim, but not as we know it

• New ideas, new questions
• Matter, Energy, and Information
• Where does the information come from?

• Identifying LifeDoes 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 dont know which
  properties of life are general and necessary, and
  which are the result of specific circumstances or
  historical accident.

Summary Definitions Properties Characteristics O
rganization Life and Energy Measuring Life Forms
of Simple Life Origin of Life
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Lecture 3 Chemistry of Life
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Chemical Bonds
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Elements

• Fundamental forms of matter
• Cant 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

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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 - H2O

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Chemical Bonds

• Electrostatic
• Covalent

• 1. Ionic Bonding
• One atom loses electrons and becomes a positively
  charged ion
• Another atom gains an electron and becomes a
  negatively charged ion
• Charge difference attracts the two ions to each
  other

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-
CHLORINE ATOM 17 p 17 e-
electron transfer
SODIUM ION 11 p 10 e-
CHLORINE ION 17 p 18 e-
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Chemical Bonds
Electrostatic Covalent

• 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

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Example
KEEP YOUR EYE ON THE ELECTRONS
slight negative charge at this end
molecule has no net charge ( and - balance each
other)
O
H
H
slight positive charge at this end
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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.

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Hydrogen bond figure
KEEP YOUR EYE ON THE ELECTRONS
Like Charge Atoms Repel Each Other
Opposite Charge Atoms Attract Each Other
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Hydrogen bonds are the most physiologically
relevant chemical bond in all of nature!!!!
one large molecule
Hydrogen bonds hold DNA strands together and
allow them to come apart and reform!
another large molecule
Hydrogen bonds take place between different parts
of a polypeptide chain and give the molecule the
glue it needs to fold correctly
a large molecule twisted back on itself
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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
• Doesnt dissolve membranes

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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

The problem with water is a static view H3O
?H2O?OH-
Draino 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
Hydrogen Ions H Unbound protons Have important
biological effects Form when water
ionizes Acids Donate H when dissolved in
water Acidic solutions have pH lt 7 Strong acids
forcefully give up H Bases Accept H when
dissolved in water Acidic solutions have pH gt
7 Strong bases forcefully take H
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Organic Compounds

• Carbons 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 - COOH-
• Phosphate group - PO3-
• Sulfhydryl group - SH

Hydrogen and other elements covalently bonded to
carbon Carbohydrates, Lipids, Proteins, Nucleic
Acids
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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

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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

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glucose
fructose
H2O
sucrose
glucose
fructose
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THE MACRO MOLECULES
Fatty acid(s)

• Lipids
• Most include fatty acids
• Fats
• Phospholipids
• Waxes
• Sterols and their derivatives have no fatty acids
• Tend to be insoluble in water
• 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

Triglycerides
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Phospholipids

• Main components of cell membranes

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Sterols and Derivatives

• No fatty acids
• Rigid backbone of four fused-together carbon
  rings
• Cholesterol - most common type in animals

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Waxes

• Long-chain fatty acids linked to long chain
  alcohols or carbon rings
• Firm consistency, repel water
• Important in water-proofing

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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

• Polyamino Acids polypeptide protein

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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

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Examples of Secondary Structure
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heme group
coiled and twisted polypeptide chain of one
globin molecule
Hemoglobin
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Denaturation

• Disruption of three-dimensional shape
• Breakage of weak bonds
• Causes of denaturation
• pH
• Temperature
• Destroying protein shape disrupts function

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A Permanent Wave
hairs cuticle
coiled keratin polypeptide chain
keratin macrofibril
one hair cell
microfibril (three chains coiled into one strand)
different bridges form
hair wrapped around cuticles
bridges broken
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A brief survey of a some protein types

• Structural
• Muscle
• Binding
• Signaling
• Storage protein
• Defensive protein
• Transportation
• Enzymes

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Structural
Function Hold together Give shape
Examples
Hair
Tendons
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Structural
Function Attachment
Collagen molecule
Collagen
A triple helix
Microfibril
Polypeptide chain
Macrofibril
Collagenous fiber
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Structural Proteins
Keratin
Actin
Crystallins
Lens Fibers
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Muscle
Function Contraction
Muscle
Flagella
Image courtesy of Dr. Fatih Uckun, Parker Hughes
Institute, St. Paul, MN
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Movement in the Cell Actin and Myosin V ATP
Dependent Reaction
Nature Reviews Molecular Cell Biology 2, 387-392
(2001)
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Signaling
Function Messengers Receptors
Insulin
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Storage
Function Store What? Expensive molecules for
later use Chemical energy
Ovalbumin- globular glycoprotein
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Protein for Defense

• Example Antibodies
• Key component of immune system
• Label invading microbes as intruders

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Transportation
Function Moving molecules In side the
organism Between cells Inside Cells Example
Getting O2 to where its needed
Hemoglobin gives blood cells their red color
61
Concepts in TransportationThe Basic Terms

• Permeability
• Diffusion - Gradients
• Membrane transport
• Active
• Passive
• Bulk

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Cell Membranes And Selective Permeability(Think
Grapefruit!)
O2, CO2, H2O,and small non-polar molecules
Sugar, and other large, polar molecules Iions
such as H, Na, CI-, Ca
X
Gradients- Unequal distributions Membranes are
required for gradients
63
Mechanisms ofCrossing Over(the membrane)

• Diffusion across lipid bilayer
• Passive transport
• Active transport
• Bulk Transport
• Endocytosis
• Exocytosis

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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

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Bulk Transport
Exocytosis
Endocytosis
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Features of Enzymes
Enzymes make, break and rearrange chemical bonds

• Enzymes make unlikely reactions happen and happen
  faster
• Enzymes arent usually reactants or products and
  usually arent used up orseverely 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)

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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
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Induced-Fit Model
two substrate molecules
substrates contacting active site of enzyme

• 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

active sight
TRANSITION STATE (tightest binding but least
stable)
end product
enzyme unchanged by the reaction
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Pulling it all together
Receptor Inhibitor Metabolic pathway Enzyme Hydrop
hobic and Hydrophillic Sterols Transport
protein

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Why is CholesterolImportant?

• Sales of Lipitor grew 25 in 2001 to 4.4
  billion. Pfizer spent 50 million on Lipitor ads
  last year.

Observational studies provideoverwhelming
evidence thatHDL-C is an independent riskfactor
for coronary heart disease
High cholesteroldoesnt care whoyou are
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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

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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
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Cholesterol and HealthWhat effects your
cholesterol level?

• Diet
• Exercise
• Genetics
• Age
• Pharmaceuticals

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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 enzymes 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.

75
Statins

• What is a good drug anyway?
• Good enzyme inhibitor- a little bit goes a long
  way (IC50)
• Specific tissue action- only works where you want
  it
• Pharmacokinetics- goes in fast and stays there a
  long time.
• Doesnt interact with other drugs

76
Cholesterol Synthesis

• Metabolic Pathway
• Linear, branched or cyclic?
• What else do we need HMG-CoA Reductase for?
• Does it only affect liver cells?

77
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)

LipophilicLipid lovingHydrophobic
How Good It Works
POLAR!
78
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 cant make
  urine, very bad)

79
Lecture 3 Chemistry of LifePart 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
80
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,
81
Hershey Chase Expt.

• 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
bacterial cell (cutaway view)
label outside cell
label inside cell
82
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)
• 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?

CovalentBonds
HydrogenBonds
83
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

84
Nucleic Acids Into Proteins
Base Pairs Are Different
DNA
RNA

• Same two steps produce ALL proteins
• 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
• 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

• 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
• Nucleotides added in 5 to 3 direction
• Unlike DNA replication
• Only small stretch is template
• RNA polymerase catalyzes nucleotide addition
• Product is a single strand of RNA

Uricil Base (U)
Sugar is Different
85
Nucleic Acids Into Proteins

• Three Classes of RNAs
• Messenger RNA (mRNA)-Carries protein-building
  instruction
• Ribosomal RNA (rRNA)-Major component of ribosome
• Transfer RNA (tRNA)-Delivers amino acids to
  ribosome
• Key Players in Translation
• Ribosome- Center of action
• The tRNAs
• Start Codon (Met)
• The tRNAs- big cast
• The mRNA- translated script
• Stop codon
• 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!

• 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
• 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
• Termination
• 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

86
Gene Transcription
Transcribed DNA winds up again
DNA to be transcribed unwinds
mRNA transcript
RNA polymerase
Growing RNA
transcript
3
5
5
3
Direction of
transcription
87
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88
Transcript Modification
unit of transcription in a DNA strand
3
5
exon
intron
exon
exon
intron
transcription into pre-mRNA
poly-A tail
cap
5
3
5
3
mature mRNA transcript
89
Genetic Code

• Set of 64 base triplets
• 4 bases, 3 positions
• Ie. 4 x 4 x 4 64
• Codon
• Sets of nucleotide bases read in blocks of three
• 61 specify amino acids
• 3 stop translation
• Stop Codons

• Twenty kinds of amino acids are specified by 61
  codons
• Most amino acids can be specified by more than
  one codon
• Example Six codons specify leucine
• UUA, UUG, CUU, CUC, CUA, CUG

90
codon in mRNA
tRNA Structure
A (second binding site for tRNA)
Binding site for mRNA
anticodon in tRNA
P (first binding site for tRNA)
tRNA molecules attachment site for amino acid
amino acid
Elongation
OH
91
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

92
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

Dont Worry About it Till After Test 1 !
93
Overview
Transcription
mRNA
rRNA
tRNA
Mature mRNA transcripts
ribosomal subunits
mature tRNA
Translation
TRANSLATIONCLIP
SUMMARYCLIP
94
When Things Go Wrong

• Mutations
• 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?

original base triplet in a DNA strand
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
altered mRNA
BASE INSERTION
ARGININE
GLYCINE
LEUCINE
GLUTAMATE
LEUCINE
altered amino acid sequence
95
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
96
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

97
Leading Causes of Deaths

• 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
98
I dont have to worry about that stuff till I get
old!
Relative to the national population of 20-24s,
are MSU students less likely to die from the top
3?

• All races, both sexes, 2024 years
• Accidents (unintentional injuries)
• Assault (homicide)
• Intentional self-harm (suicide)
• Cancer
• Heart disease
• Genetic abnormalities
• Human immunodeficiency virus (HIV)
• Stroke
• Influenza and pneumonia
• Diabetes

Its difficult for one to prevent bad luck, or
being a victim?
99
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

100
Diabetes Mellitis

• Cells in muscles, liver and fat dont 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 dont heal

101
Risk Factors

• Age
• Overweight
• Inactive (exercise gt 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

102
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

103
Control of Glucose Metabolism
insulin
Glucose is absorbed
Glucose uptake
Glucose to glycogen
Glucose falls
Cells use glucose
Glucose rises
Glycogen to glucose
glucagon
104
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
FAT GLOBULES
MICELLES
carbohydrates
EMULSIFICATION DROPLETS
proteins
EPITHELIAL CELL
CHYLOMICRONS
INTERNAL ENVIRONMENT
105
Energy from Macromolecules

• Energy Reserves
• Glycogen is about 1 of the bodys 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-6-phosphate
• 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
• Glucose is used to make ATP first
• When ATP store is full, glucose is stored
• Glycogen is a big branched polymer of stored
  glucose
• Glycogen isnt very soluble so it is trapped
  inside the cell where it is stored.

106
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, 2Cs at a time
• Before it can even enter Krebs Cycle

107

• 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
• Dont 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)

108
Overview of Aerobic Respiration
CYTOPLASM
glucose
ATP
GLYCOLYSIS
energy input to start reactions
(2 ATP net)
e- H
2 pyruvate
2 NADH
MITOCHONDRION
e- H
2 CO2
2 NADH
e- H
4 CO2
8 NADH
KREBS CYCLE
e- H
2
ATP
2 FADH2
e-
ELECTRON TRANSPORT PHOSPHORYLATION
32
ATP
H
water
e- oxygen
TYPICAL ENERGY YIELD 36 ATP
109

• 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

• Main Pathways Start with Glycolysis
• 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 oxygen carbon 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

110
Overview of Aerobic Respiration
CYTOPLASM
glucose
ATP
GLYCOLYSIS
energy input to start reactions
(2 ATP net)
e- H
2 pyruvate
2 NADH
MITOCHONDRION
e- H
2 CO2
2 NADH
e- H
4 CO2
8 NADH
KREBS CYCLE
e- H
2
ATP
2 FADH2
e-
ELECTRON TRANSPORT PHOSPHORYLATION
32
ATP
H
water
e- oxygen
TYPICAL ENERGY YIELD 36 ATP
111
Aerobic Respiration

• Whats the deal with Oxygen?
• 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
• Pull a hydrogen off a water (HOH to OH-)
• Pull the hydrogen (H) across a membrane
  (electrochemical GRADIENT)
• Make the H do work on its way back to OH-

• Coenzyme Production
• Key Concepts Coenzyme production
• Krebs cycle produces activated coenzymes
• 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.htm
l
112
(No Transcript)
113

• Fermentation 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
• Bakers yeast
• Carbon dioxide makes bread dough rise
• Saccharomyces ellipsoideus
• Used to make beer and wine
• MSU hard cider project Sacchromyces banyan DV10

• Anaerobic Pathways
• 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
• Doesnt require Oxygen
• Cant work with Oxygen
• ATP yield is low
• Lets bacteria live where other organisms cant

114
Lactate Fermentation
GLYCOLYSIS
C6H12O6
ATP
2
energy input
2 NAD
2 ADP
NADH
2
ATP
4
2 pyruvate
energy output
2 ATP net
LACTATE FORMATION
electrons, hydrogen from NADH
2 lactate
115
Alcoholic Fermentation
GLYCOLYSIS
C6H12O6
ATP
2
2 NAD
energy input
2 ADP
NADH
2
ATP
4
2 pyruvate
energy output
2 ATP net
ETHANOL FORMATION
2 H2O
2 CO2
2 acetaldehyde
Animals Cant do this!
electrons, hydrogen from NADH
2 ethanol
116
Processes Are Linked

• Aerobic Respiration
• Reactants
• Sugar
• Oxygen
• Products
• Carbon dioxide
• Water

• Photosynthesis
• Reactants
• Carbon dioxide
• Water
• Products
• Sugar
• Oxygen

117
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

118
Summary of Photosynthesis

• 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

light
LIGHT-DEPENDENT REACTIONS
6O2
12H2O
ATP
NADPH
NADP
ADP Pi
PGA
CALVIN-BENSON CYCLE
PGAL
6CO2
RuBP
P
C6H12O6
(phosphorylated glucose)
end product (e.g. sucrose, starch, cellulose)
119
Machinery of Noncyclic Electron Flow
H2O
photolysis
e
e
ATP SYNTHASE
NADPH
NADP
ATP
ADP Pi
PHOTOSYSTEM I
PHOTOSYSTEM II
120
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, a