Lecture 3: Chemistry of Life
Part 3 of 2
Same song
Second verse
A little bit louder
And a whole lot worse
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 (1°,2°,3°,4°), peptide bond, lipoprotein,
glycoprotein, diffusion, permeability, transport, gradient
Assingment:
For Tuesday, read Ch 12 and 13
For Thursday, read Ch 8 and 14
Amino Acid Structure
amino
group
carboxyl
group
R group
Properties of Amino Acids
• Determined by the “R group”
• Amino acids may be:
– Non-polar
– Uncharged, polar
– Positively charged, polar
– Negatively charged, polar
Amino acids
If you memorize the
single and three letter
abreviations, the
chemical structure, the
pKa and the relative
hydrophobicity for each
amino acid, then you are
a student of
biochemistry and do not
belong in this class.
HC
H3C
3
C
H C3H
2H C
C
H N2H
O
H
C
S
H2C
HC
CH2
C
H2N H
HO
HN
2
HC
C2H
H3C H OH
C
2
2H C
O
C2H
C
H NH
2
C
H2N H
Threonine
C
N H
H
H
C
HO
CH2
C
H
C
H2N H
H3C H CH3
C
CH2
C
H2N H
O
Serine
C
H2N H
O
H
N C
Valine
2H C
C
H
C
H NH
2
O
•R-groups help
to determine the
intramolecular
arrangement of
a protein
C
H
H
N
NH 2
O
CH2
O
H2C
OH
3H C
3H C
O
H C2H
C
C
H N2H
CH2
H2N
C
H2N H
O
C
H2N H
O
CH2
O
C
H2N H
OH
OH
OH
Arginine
Alanine
HS
H2N
CH2
C
H2N H
O
CH3
HO
enicuelosI
HO
CH2
HO
eniditsiH
O
HN
CH3
O
OH
OH
Tyrosine
NH
•The R-groups
are different
O
OH
CH
C
H
OH
Tryptophan
H2N
CH2
C
H2N H
O
Proline
HC
HN
HO
OH
Phenylalanine
H H
C C
HC
CH
OH
HO
enisyL
H2C
O
OH
O
C
H2N H
H2 H
C C2
CH2
C
H
O
OH
Methionine
enicueL
CH
HC
H2C
Asparagine
HO
O
H2C
CH2
C
H2N H
O
OH
Cysteine
Glutamine
Aspartic Acid
O
H2
C
CH2
C
H2N H
O
OH
Glutamic Acid
H2N
O
OH
Glycine
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
Chemical Reaction
Condensation of Amino Acids is the
formation of a peptide bond
Protein = chain of amino acids
Forming Peptide Bonds
We need a vocabulary for
describing proteins
1. General shape
2. Level of detail we are talking about
Identity
Homology
3D Structure
1. General function of the 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
• Sequence of amino acids
• Unique for each protein
• Three or more = polypeptide
• Backbone of polypeptide has nitrogen
atoms (not just a hydrocarbon):
– -N-C-C-N-C-C-N-C-C-N-
Secondary Structure
• Hydrogen bonds form between different
parts of polypeptide chain
• These bonds give rise to coiled or
extended pattern
• Helix or pleated sheet
Examples of Secondary
Structure
a-helix
b-sheet
Tertiary Structure
heme group
Folding as a result
of interactions
between R groups
coiled and twisted polypeptide
chain of one globin molecule
Quaternary Structure
Some proteins
are made up of
more than one
polypeptide
chain
Hemoglobin
Polypeptides With Attached
Organic Compounds
Nothing new! Just more combinations of
Tuesday’s vocabulary
• Lipoproteins
– Proteins combined with cholesterol, triglycerides,
phospholipids
• Glycoproteins
– Proteins combined with oligosaccharides
Denaturation
• Disruption of three-dimensional shape
• Breakage of weak bonds
• Causes of denaturation:
– pH
– Temperature
• Destroying protein shape disrupts
function
Protein Restoration
Renaturing proteins
Refolding ?
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
QUIZ 1
Quiz ISB-202
1- Is it always wrong to kill another human being?
A. It is always wrong to kill another human being (Morally wrong).
B. It is OK if one is defending one’s family or property (Self-defense).
C. It is OK if the majority of Americans vote for it (Voters say its “OK”).
D. It is OK if it does not break the Law (Supreme Court say its “OK”).
E. Since all life is related and descendant from more primitive forms, killing a
human is not different than killing a germ (No moral reason not to).
2- None of the above describes my view of killing another human. T/F
3- How do you know that something is absolutely true?
A. Absolute truth is a Revelation from God. (Only from Bible, Koran or other
Holy book).
B. There is no such thing as Absolute Truth, only approximate truth through
the scientific method (Scientific Imperialism).
C. All truth is relative, an antecedent of personal environment, experience and
education (postmodern relativism).
D. Truth is only found in the mind; that is, we develop our own truth through
our thought processes (existential ontogeny: “I think, therefore, I am”
Rene’ Descartes).
E. Truth is an operational logical proposition to be used in creating “models”
of reality. It is an emergent awareness and self-discovery process wholly
contained in culture (social evolution).
4- None of the above describes my view of truth. T/F
2345- In today’s western societies there are several popular models of life’s origin.
Which of the following most nearly describes your perspective?
A. Life came from 4+ billion years of evolution on earth.
B. Life came from 4+ billion years of evolution on earth, but God started
the process (God is like a “Blind Watchmaker”: He started it but
doesn’t do anything now).
C. Life came from 4+ billion years of evolution on earth, but God started
the process and has remained active in His creation directing changes
through evolution.
D. God created everything from nothing 4 + billion years ago, but allows
small changes within different kinds of plants and animals through
evolution.
E. God created everything from nothing in 7 days (counting a day of
rest) about 10,000 years ago.
6- None of the above describes my view of life’s origin. T/F
7- I think that genetically modified organisms are:
A. Good because they will provide another step in man’s progress.
B. Good, but society must limit their bad uses.
C. Bad because man is not wise enough to use this technology yet.
D. Bad because engineering life, if and when science can do that, violates
God’s laws or His dominion (control) over life.
E. None of the above describes my view of genetically modified
organisms.
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
Types of protein
•
•
•
•
•
•
•
•
Structural
Muscle
Binding
Signaling
Storage protein
Defensive protein
Transportation
Enzymes
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)
Types of protein
•
•
•
•
•
•
•
Structural
Muscle
Signaling
Storage protein
Defensive protein
Transportation
Enzymes
Signaling
Function:
Messengers
Receptors
Insulin
Insulin
In
Action
Types of protein
•
•
•
•
•
•
•
Structural
Muscle
Signaling
Storage protein
Defensive protein
Transportation
Enzymes
Storage
Function:
Store What?
Expensive molecules for later use
Chemical energy
Ovalbuminglobular glycoprotein
Types of protein
•
•
•
•
•
•
•
Enzymes
Structural
Muscle
Signaling
Storage protein
Defensive protein
Transportation
Protein for Defense
• Example: Antibodies
• Key component of immune system
• Label invading microbes as intruders
Types of protein
•
•
•
•
•
•
•
Structural
Muscle
Signaling
Storage protein
Defensive protein
Transportation
Enzymes
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
General Characteristics
• 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
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
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
Bulk Transport
Exocytosis
Endocytosis
Types of protein
•
•
•
•
•
•
•
•
Structural
Muscle
Binding
Signaling
Storage protein
Defensive protein
Transportation
Enzymes
Enzyme Structure and
Function
Enzymes are catalytic molecules
They speed the rate at which reactions
approach equilibrium
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
Induced-Fit Model
substrates
contacting
active site
of enzyme
active sight
TRANSITION
STATE
(tightest
binding but
least stable)
end
product
enzyme
unchanged
by the
reaction
• 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
Observational
studies
provide
25% in 2001 to $4.4
overwhelming
billion.
Pfizer spent $50evidence that
million
on Lipitor
HDL-C
is anads
independent risk
last year.
factor for coronary heart disease
High cholesterol
doesn’t care who
you are
Disclaimer
1. I am a PhD not an MD
2. Genuine exchange of scientific
information vs. medical advice
3. I’m un-sponsored
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
Cholesterol and Health
•
•
•
•
•
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.
What is a good drug?
Statins
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
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
Nucleic acids =
Macromolecules
or the Information Molecules of Life
Gene =
Basic unit of
inheritance =
“Passing the
torch”
DNA = •Deoxyribonucleic
acid
•Polynucleotide
Nucleotide =Building block of nucleic acids
Nucleotide Structure
• Sugar
– Ribose or deoxyribose
• At least one phosphate group
• Base
– Nitrogen-containing
– Single or double ring structure
Phosphate
+
Sugar
Base
= Nucleotid
e
(Deoxyribose)
H
C
O
+
H
O
Purine
O
-Adenine (A)
O
P
O
C
C
O
H
C
OH
C
H
-Guanine (G)
H
Pyrimidine
-Thymine (T)
-Cytosine (C)
DNA
Phosphate
+
Sugar
Base
= Nucleotid
e
(Ribose)
H
C
O
+
H
O
Purine
O
-Adenine (A)
O
P
O
C
C
O
H
C
OH
C
OH
-Guanine (G)
H
Pyrimidine
-Thymine (T) Uracil (U)
-Cytosine (C)
RNA= messenger (m), ribosomal (r),
transfer (t) e.g. mRNA, rRNA & tRNA
Two views of the DNA molecule
DNA is a helix
Pairs of nucleotides
make up the “rungs” of
the “ladder”
Nucleotide Functions
• Energy carriers
• Coenzymes
• Chemical messengers
• Building blocks for
nucleic acids
Careful: Nucleotide isn’t just DNA or RNA
Nucleic Acids
Cytosine
Adenine
• Composed of nucleotides
• Single- or double-stranded
• Sugar-phosphate backbone
Nucleotides
Base
3 phosphate groups
Sugar
CYTOSINE
GUANINE
ADENINE
THYMINE
Fig. 3.19, p. 46
DNA
• Double-stranded
• Consists of four
types of
nucleotides
• A bound to T
• C bound to G
RNA
• Usually single strands
• Four types of nucleotides
• Unlike DNA, contains the base uracil in
place of thymine
• Three types are key players in protein
synthesis
Natural Toxins
• Normal metabolic products of one
species that can harm or kill a
different species
• Natural pesticides
– Compounds from tobacco
– Compounds from chrysanthemum
Synthetic Toxins
Atrazine
DDT
Malathion
Atmospheric Carbon Dioxide
• Researchers have studied
concentration of CO2 in air since the
1950s
• Concentration shifts with season
– Declines in spring and summer when
producers take up CO2 for photosynthesis
CO2 and Global Warming
• Seasonal swings in CO2 increasing
• Spring decline starting earlier
• Temperatures in lower atmosphere
increasing
• Warming may be promoting increased
photosynthesis
Humans and Global Warming
• Fossil fuels are rich in carbon
• Use of fossil fuels releases CO2 into
atmosphere
• Increased CO2 may contribute to global
warming
Producers Capture Carbon
Using photosynthesis, plants and
other producers turn carbon dioxide and
water into carbon-based compounds
Bioremediation
Use of living organisms to
withdraw harmful substances
from the environment
Negative Effects of Pesticides
• May be toxic to predators that help fight
pests
• May be active for weeks to years
• Can be accidentally inhaled, ingested,
or absorbed by humans
• Can cause rashes, headaches, allergic
reactions
Polyunsaturated Fatty Acids
Omega-3
•Omega-6 fatty acids are the
predominant polyunsaturated fatty
acids (PUFAs) in the Western diet.
•The omega-6 and omega-3 fatty acids
are metabolically distinct and have
opposing physiologic functions.
Omega-6
•The increased omega-6/omega-3 ratio
in Western diets most likely contributes
to an increased incidence of heart
disease and inflammatory disorders.
•Omega-3 PUFAs suppress cell
mediated immune responses and
reduce inflammation
Lipids in Cell Signaling
•Bioactive Lipids
•Made in all cells
•Short range signaling
•Eicosanoids?
•Prostaglandins
•Inflammation and Pain Perception
•Kidney Function
•Bone Development
•Reproductive Process
•Commercially Important
•$4 BILLION/ Year spend on drugs
to inhibit prostaglandin synthesis
•Vioxx, Celebrex, Ibuprofen, Asprin
PGE2