Controls shape, motility, cellular division, and as track for motor patients
Sense forces and regulates gene expression
Three components:
- Microfilaments (polymer of actin)
- Intermediate filaments (chains)
- Microtubules (long hollow cylinders made up of tubulin)

Lecture 3: The Chemistry of Life

“Compounds and Elements of life”

Organismal matter:

Mostly compounds

Compound:

Contains two or more different elements in a defined ratio

Major elements in the human body:

C, H, O, N

Trace elements:

Rare but are still crucial:
Iron in hemoglobin
Iodine in thyroid hormone

Molecules:

Defined by two or more atoms covalently bonded together

What are weak bonds?

Bonds that form electrostatic attraction between two groups
- Hydrogen bonds
- Ionic bonds
- Van der Waals interactions

Hydrogen bonds:

Hydrogen is covalently bonded to another atom and develops a positive charge becomes attracted to a partially negative charge somewhere nearby
EXTREMELY IMPORTANT

Ionic Bonds:

Defined of a mix of multiple elements that aren't covalent bonds
Like NaCl
Strength depends on conditions

Van der Waals Interactions:

Determine the following
- 3D shape of proteins
- Specific interaction between enzyme and its substrate
- Specific interaction of antigens-antibody interactions

“Water in a Biological Context”

Why is Water so special?

Most abundant compound on earth
Neutral but polar
And partial + and - churches provide structure for liquids and solids:

Properties of water

(1) - Adhesion and Cohesion:
- Adhesion to other polar or charged molecules
- Cohesion to other H2O: resists deformation
(2) - Moderation of Water Temperature:
- Has high specific heat
- Sweating
(3) - Solid H2O is less dense than Liquid H2O
- Ice floats
- Insulates the liquid underneath
- Allow marine organisms to flourish
(4) - Acts as a Solvent for other molecules
- Water dissolves Polar and Charged molecules
  - Hydrophilic
- Is a universal solvent

Acids:

Increase the relative concentration of H3O+ in a solution (H+)
Decreases the concentration of OH-

Base

Decreases the relative concentration of H3O+ in a solution (H+)

Increases the concentration of OH-

pH:

The concentration of H+ is 10^-7 → pH = 7.0
pH scale ranges from 0-14

How are Cells sensitive to changes in pH:

Changes in pH can change the ionization state of Macromolecules
- Changes in charge = Change in structure = Change in Function

“Carbon and Bio-Molecular Diversity”

Carbon the Element

6 Protons and 6 electrons
4 electrons in the outer valence shell

Hydrocarbons

Molecules consisting of only Hydrogens and Carbon
Diverse, complex, non-polar
Ex. Beeswax

Four basic types of abundant biomolecules

Carbohydrates
Lipids
Nucleic Acids
Proteins

Macromolecules

Built from linking monomers into a covalently bonded chain called a polymer

Protein synthesis

An unlinked monomer is added to a polymer chain by removing a water molecule to form a new bond
Process known as dehydration and 1 water molecule will be released for every monomer added to the polymer

Protein disassembly

A polymer adds a water molecule to remove a monomer from a polymer
Known as Hydrolysis

Carbohydrates are also sugars:

Monosaccharide: one sugar molecule
Disaccharide: two monosaccharides
Polysaccharide: 3-10 monosaccharides
Oligosaccharide: many monosaccharides

What are monosaccharides common structure

(CH2O)n
N =3-7 typically

How are a- and b- glucose isomers defined?

A- C1 has OH facing down
B-C1 has an OH facing up

Glycosidic (sugar-sugar) bonds

Glycosidic bonds have a A- and B- orientation
Ex. maltose uses a a- glycosidic bonds

Functions of Polysaccharide:

Energy storage
- Starch in plants
- Glycogen in animals
Structure and Protection
- Cellulose in plant cell walks
- Chitin: Fungal cell walls, arthropod exoskeletons
- Peptidoglycan: bacterial cell walls

What are the similarities between starch and glycogen

Both are polymers of glucose but use different isomers for the monomer, and a different type of glycosidic bond between them
Branched loosely packed, and easily broken down.
Difference
- Cellulose monosaccharide is a beta glucose and starch is an alpha glucose

Chitin and cellulose similarities

They form long tightly packed long chain

Lipids:

Energy Storage, Biomembranes, Honormones

What are lipids?

Diverse molecules
- Have no common structure
- Include fats, phospholipids, pigments, vitamins, waxes and steroids
Characterized by hydrophobicity
Large but are not true polymers

Glycerol

3-carbon polyalcohol

Fatty Acids

Unbranded hydrocarbon chain
Carboxyl group (-COOH) at one end

Neutral Fats:

Built by linking smaller molecules through dehydration synthesis
Ex. Monoglyceride, triglyceride

Saturated vs unsaturated Fatty acids.

“Saturated” molecules have no no double bonded C=C
“Unsaturated ” have at least one C=C bond → causes kink

Animal lipids vs Plant lipids:

Animals
- Usually saturated
- Fatty acid tails are packed tightly
- Solid at room temperature
- Fats
Plants
- Usually unsaturated fatty acids
- Pack more loosely
- Liquid at room temperature
- oils

Phospholipids:

Component of biomembranes
Spontaneously self assemble into lipid bilayer
Bilayer segregates inside from outside
Amphipathic

Head and tail of Phospholipid

Head-hydrophilic
Tail- hydrophobic

Steroids:

4-carbon rings
Derived from cholesterol, a membrane lipid
Differ in placement and structure of functional groups

Glucocorticoids

Cortisol

Sex steroids

Estrogen and testosterone

Lecture 4- Nucleic acids

Nucleic acids?

Unbranched chains of covalently bonded nucleotide monomers
Can be a very long
Two types:
- Ribonucleic Acid
- Deoxyribonucleic Acid

Structure of Nucleic Acids

Monomor is a nucleotide with three parts
- 5C sugar
- Nitrogenous base
- 1-3 phosphate groups

Nucleoside

Base and sugar

Nucleotide

Base, sugar, and phosphate

Two types of pentose sugar:

Presence of Oxygen on 2’ Carbon → ribose
Absence of Oxygen on 2’ Carbon → deoxyribose

Nitrogenous Bases

Pyrimidines (6 sided rings)
- thymine, cytosine, uracil
Purines: (fused 6 sided and 5 sided rings)
- Adenine and guanine

Building nucleoside

Bases are attached at to the 1’C of sugar
-Suffixes
- - sine for purines
- - dine for pyrimidines

Building nucleotides

Phosphates attached to 5’C
Name species of phosphate count

Phosphodiester Bonds

Esters have the form R-C(O)OR
Replacing with P gives you a phosphodiester R-P(O)OR
Nucleotides of both RNA and DNA are joined through Phosphodiester bonds

Nucleic acid polymer

Have polarity
3’ end -OH
5’ end phosphate group

Model of DNA

Two antiparallel strands of opposite polarity
Sugar-phosphate backbone
Point towards center

Watson-Crick-Wilkins-Franklin* Model

DNA base pairing
- A-T
- A-G
Base pairs held by hydrogen bonds
Stacked of bases along a helix stabilized by van der Waals interactions

RNA

Carries genetic information
Catalyzes reactions
Selection favors variants with effective replication

Lecture 5- Proteins

What purpose do proteins serve?

Proteins form an infinite variety of shapes and higher order structure
Proteins shapes and assemblies can respond rapidly to subtle modifications
Protein structure and activity control almost everything that cells do

What are protein functions?

Catalysts
Structure
Communication
Transport
Motility
Defense
Recognition
Regulation
Storage

Protein Structure

Protein are unbranched polymers
Monomer is the Amino Acids
20 different AA

How Many peptide sequences can exist

20^n
General solution for peptide of length is N

Individual Amino acid Structure

Amino group
Carboxyl group
H
R-group
All are bound by a Central carbon
Non R is the backbone that is identical for 19-20 of the amino acid
R-group determines the chemical and physical properties of AA

Charged AA

Positive: Basic → R groups pick up H+ and increase pH
Negative : Acidic → R groups loose an H+ and decrease pH

Polar Uncharged AA

All have a terminal O

Non-polar (Hydroponic)

Hydrocarbons

Special cases

Cysteine:can form S-S bridges with other cysteines
Glycine: Only H atom for R-groups
Proline: forms second bond with backbone

Polymer Formation

Polymer = Polypeptide
Dehydration synthesis
Carboxyl to Amino group

Polypeptide vs Protein

Protein: 1 or more complete polypeptide folded into a specific 3D conformation
Polypeptide : Linear sequence of covalently bonded amino acids

Protein Conformation and Function:

Function requires specific shape
Proteins fold spontaneously into specific confirmation
- Globular or Fibrous

Four levels of Protein Structure

Primary
Secondary
Tertiary
Quaternary

Primary structure of Proteins

AA joined forming polypeptide chains
Stabilized by peptide bonds
Sequence is genetically determined

Secondary structure of Proteins:

Polypeptide chains may form Alpha helices or beta-pleated sheets
Stabilized by hydrogen bonds within backbone

Tertiary Structure of Proteins

Molecular interactions between R- groups within the same polypeptide
Bonds include
- H-bonds
- Van der waals
- Disulfide bridge
- Ionic Bonds

Quaternary Structure of Proteins

Only found in multi subunit proteins

Disulfide Bonds in Proteins

When two cysteine amino acid residues come close together → sulfur atoms form covalent bond known as a disulfide bonds
Extremely stable and lock proteins into shape
From within or between polypeptide

Protein Folding:

Occurs simultaneously with synthesis
Energetic and entropic consideration determine the final form
Structure that minimize internal energy are favored
temperature , Ionic strength, pH affect the final structure

Denatured protein

Protein that lost its original structure due to changes in conditions
Sometimes it can't be reversed

Protein folding and disease

Misfolded proteins cause common disorders
Due to mutations or disruption of normal folding processes
- Ex. Parkinsones, Alzheimers, Cystic fibrosis, Mad Cow Disease, Progressive supranuclear palsy (PSP), Emphysema

Sickle Cell Disease

Caused by a change of just one amino acid change in the hemoglobin polypeptide
polar and charged GLU changes to a nonpolar side chain in Val

Protein Modifications that alter structure and function

Ligand binding
Covalent R-group modification
Addition of cofactors
Proteolytic cleavage

What is ligand binding?

Unbound ligand binds to a protein causing protein to change its shape

What is R-group Modification?

The addition of a chemical group to an amino acid changes its interaction with other AA and proteins will change shape
- Phosphorylations
- Protein kinase
- Protein phosphatase

What is the addition of a cofactor?

A cofactor is generally a constant feature of a protein → sort of activates protein
Examples
- Iron and heme allow hemoglobin to carry Oxygen in the blood
- Kinases have different shapes when bound to ATP versus ADP

Proteolysis:

Part of the initially synthesized enzyme blocks the active site and proteolytic cleavage of part of the enzyme exposes the active site which will activate the enzyme
Can create a signal in a cell

Phosphorylations

Addition of phosphate group (PO4)

Protein kinase

The enzyme that adds phosphate to R groups of serine, threonine, or tyrosine

Protein phosphatase:

Removes phosphates

Lecture 7- Energy Transform and Biochemistry

Metabolism

Collection of all biochemical reaction occurring in a cell
Often grouped in pathways
- Product of one rxn is often the substrate of another

Catabolism

Catholic pathways BREAK DOWN larger complex molecules into smaller less complex molecules
- Reduces unused molecules and generates monomers
Releases chemical energy and provides building-block molecules for other cellular process

Describe a simple model of catabolism

Breaks down large molecules → releases a useful forms of energy and Heat → leaves building blocks

Anabolism

SYNTHESIS larger molecules from smaller molecules
Requires energy input

Describe a simple model of Anabolism

Many molecular subunits → take useful forms of energy and lost heat —> larger molecules

Energy

Capacity to cause a change against a force

Kinetic Energy

Energy associated with the motion of matter

Thermal Energy”

Heat
Amount of kinetic energy in matter: vibration, rotations, diffusion of atoms and molecules

Potential Energy:

Energy stored in matter because of its location

Chemical energy:

Potential stored in chemical structure

Thermodynamics

Study if energy transformation in a collection of matter

System and Surroundings

System: whatever is being studied
Surroundings: Anything not in the system

Laws of thermodynamics:

1st law of thermodynamics: Energy is Conserved
- The total energy in the universe is neither created nor destroyed
2nd law of thermodynamics: Entropy (S) of the universe can only increase
- Entropy is disorder
- Efficiency is lower than 100%
- Any decrease in entropy of the system must be paid for by increase in entropy in the universe

Energy Accounting

Total energy in a system is H
Toral free energy in a system is G
Total entropy in a system is S
Absolute temperature is T

Equation that puts the two laws together in one equation

∆H = ∆G + T∆S
Negative ∆G means reactants have more free energy

Types of Cellar Work

Chemical work: Anabolic reactions
Mechanical Work: Directed movement
Transport Work: Building gradients
Bioluminescence: Generate light

What does Cellular work dp?

Causes use chemical energy, usually ATP, to drive nonspontaneous processes forward

Why do lipid Bilayers form spontaneously? And is Entropy favored?

Individual lipid molecules in aqueous solution are surrounded by ordered arrays of water molecules
When lipids assemble the water is releases increasing entropy → assembly is favored
Spontaneous local order maximizes universal disorder

Hydrophobic interaction?

Non-polar molecules don’t repel or attract each other
In comparison polar molecules and ions do
The polar and charged molecules squeeze hydrophonic regions together → know as the hydrophobic effect

Energetic of Protein folding Unfolded vs. Folded state? Entropy within the system?

Unfolded state
- Polypeptide: Various configurations with exposed amino acids (intermediate S)
- Adjacent water Molecules: Ice like shells exposed to the AA (Low S)
Folded state:
- polypeptide : Active protein with hydrophobic AA inside (Low S)
- Adjacent water molecules: Moving freely (very high s)

Thermodynamic Definition of a Cell?

Cells are open systems that
- 1) use thermodynamically favored processes to transform available energy and matter into life forms
- 2) use high free energy (delta G) for carrying out life's processes
- 2) Release low quality energy (heat)
- 3)maintain order structures at the cost of increased universal disorder

Lecure 8- Energy, ATP, nad Enzymes:

How is life about “work”?

The ability to acquire and use energy is a fundamental property of all living organisms
In cells, energy is the ability to do works
Ex: Biosynthesis, mechanical activity, active transport, bioluminescence

Are all Reaction pathways for biological work endergonic or Exergonic?

Endergonic (+delta G)!
This condensation rxn moves to the left
Many endergonic rxn use free energy
- Form the hydrolysis of ATP bonds
To move to the right requires input of energy

Adenosine Triphosphate (ATP) as a carrier for Energy

ATP phosphate groups are closely set and all negatively charged
Repel each other and joined by Phosphodiester bonds
Hydrolysis of terminal takes some energy however it creatures stable product releases free energy

ATP Hydrolysis

1+ terminal phosphate groups are removed from ATP by hydrolysis
Highly exergonic

Endo-(Endergonic)

Input of energy
Inside or within
+ΔG
Non-spontaneous
“Building of molecules”

Ex- (Exergonic)

Releases energy
Out
- ΔG
Spontaneous
“‘Breaking of molecules”

What determines whether a chemical reaction moves forward?

All rxn are theoretically reversible A <->B
Facotable rxn move forward
Rxns at equilibrium or endergonic cannot move forward

What is a favorable cellular rxn?

Hydrolysis of sucrose into Glucose and fructose

What is a cellular rxn that does not occur?

Sucrose + water

What is a catalyst?

They accelerate a rxn without being permanently changes
An enzyme
- Proteins
- Or Ribozyme for RNA

Anatomy of Chemical Rxn

Involve breaking or rearranging bonds
High energy, unstable intermediate called transition state
Need sufficient energy to reach transition state
REMEMBER INTRO TO MECHANISMS (CONDENSED GRAPH)

Why is Activation energy needed for a rxn to be complete? (

Energy must be available to raise reactants to Transitions tate
Energy release when old bonds are broken and new bonds are formed
Products assume lower energy more stable

What is Activation Energy (E_A)> What is a low and high barrier?

Serves a barrier to rxn progression and completion
- Low Barrier: many reactant molecules have sufficient energy
- High barrier: few reactants have sufficient energy

Enzymes lower activation energy, but how?

Enzymes for a enzyme-subtrate complex
Enzymes couple ATP hydrolyis to mayke the unfavorabel favorable

Active Site:

Substrates bind at the Active Site
- Groove or pocket exposed on the surface of enzyme
- Not rigid structure
- A small portion of the Enzyme protein structure
- Formed by a noncontigoius amino Acid

Specificity of Substrate Binding

Presence of substrate changes shape of enzyme to form tight complex
Induced Fit

Steps for Enzyme-substrate complexes breaking molecules

1) Substrates enter
2) Substrates held in the active site by weak interactions
3) Substrates converted to products
4) Products are released
5)Active site it now available

Concept Checks & GAE Questions!!

Which of these statements is TRUE about the relationship between structure and function in biology?

Structure and function are related at all scales of biology

Which of these microscopes has the highest resolution (can see the smallest object)?

Electron microscope

Which of the following is a true statement regarding prokaryotes and eukaryotes?

Eukaryotes formed by a symbiotic merger of archaea and bacteria

Which of the following structures in a eukaryotic cell are formed from the protein actin?

microfilaments

True/False: Spontaneous (= exergonic) processes always happen quickly with no energy input

False

True/False: Cells have no way of achieving condensation reactions, because they are endergonic (have a positive delta G).

False

Which of these statements is the best description of how ATP carries chemical potential energy?

Negatively charged phosphates repel each other, but are held together, like the ends of a compressed spring.

Which of these is NOT a function of ATP?

Catalyzing reactions

Which of the following is the best statement for what enzymes do?

Enzymes lower the activation energy for an otherwise favorable process.

Lysosome

Storing digestive enzymes

Rough ER

Protein synthesis

Smooth ER

Cholesterol synthesis

Golgi Apparatus

Processing proteins for secretion

Mitochondria

ATP synthesis

Chloroplast

Starch production

The pancreas is an organ that secretes proteins into the gut to help digest food. Which of the following organelles would you expect to be present in unusually large amounts in the cells doing this secretion?

Rough endoplasmic reticulum

Ribosomes are NOT found in, or associated with, which of the following?

Gologi Apparatus

TRUE/FALSE: Defects in one of the cytoskeleton systems would be expected to alter the shape of a cell, or its ability to respond to stimuli.

True

TRUE/FALSE: Trace elements are not important to biology because they occur in such small amounts in life.

False

If there is a concentration of [H+] in water of 10-4 , which of the following statements is most accurate?

It has a pH of 4, which is acidic

Which of the following is the best description of a hydrogen bond?

It is the attraction between a partially positive H atom and another nearby atom with a partial negative charge (e.g N or O).

What is the name of the bond between individual monosaccharides in a polysaccharide?

Glycosidic linkage

The R groups of amino acids have certain properties that allow for amino acids to be organized into five groups with similar properties. Which of the following group descriptions is NOT one of thes?

Positively charged and hydrophillic

Which interactions are not involved in the formation of a protein's tertiary structure?

Peptide bonds

Tertiary and quaternary structures share all the following properties except

Subunit-subunit interactions

A peptide linkage forms between . . .

An amino group nad a carboxyl groups

Which statement about the structure of a protein is true?

A gene mutation that causes a single amino acid substitution in the primary sequence of a protein can cause a significant change in the protein's tertiary structure.

What three components form the structure of a nucleotide?

Pentose sugar, nitrogen-containing base, and a phosphate group

Which single-stranded DNA molecule will bind in a complementary fashion to this single- stranded DNA molecule? [HINT: Pay attention to both the polarity of the strands AND the order of the bases] 3' A-T-G-A-A-C-T-G 5'

5ʹ T-A-C-T-T-G-A-C 3ʹ

Which of the following would be true of any given double-stranded DNA molecule?

It would contain an equal number of purines and pyrimidines.

True or false? "Unlike DNA, the bases of RNA never form complementary pairs with other

RNA bases."

False

Each of the amino acids has a fundamental structure composed of a central carbon (the alpha carbon) bonded to…

one hydrogen atom, one carboxyl group, an amino group, and one R group.

Two of the twenty amino acids are acidic and three others are basic at cellular pH values. Which properties do these five amino acids share?

Hydrophilic

The average length of a polypeptide is about 350 amino acid monomers. How many possible primary structures could theoretically exist for a polypeptide just 36 monomers in length?

6.9 x 1046

Which one statement provides the best [= most complete and accurate] explanation for why primary structure is largely responsible for determining the tertiary structure of a polypeptide?

The primary structure specifies the types, number, and order of all the amino acids in a protein.

An inhibitor that binds to the active site of an enzyme is termed a(n)

Competitive inhibitor

Whereas an inhibitor that binds to a site distinct from the active site is termed a(n)

Allosteric

These are both examples of ____ inhibition if the inhibitors bind using noncovalent forces of attraction.

Reversible

The activity of an enzyme was examined in the laboratory as it catalyzed the formation of a product molecule, B, from a substrate, A. This reaction was carried out in an aqueous solution consisting of water and copper sulfate at a pH of 7. While attempting to repeat the experiment, a biochemist uses a solution of pure distilled water (pH = 7) and observes that the rate of formation of B has decreased dramatically. Which is the best possible explanation for this result?

The enzyme needs copper ions to act as cofactors for optimal enzyme activity.

Which statement accurately describes features of the active site of an enzyme?

Its shape is specific for the substrates.

If you wanted to permanently block the function of an enzyme, you could

add a molecule that can covalently bind to the active site.

Alcohol dehydrogenase (ADH) catalyzes the oxidation of ethanol (CH3CH2OH) to acetaldehyde, which is then fed into pathways to make fatty acids or to be used as a fuel source. The human body can therefore tolerate a certain amount of ethanol. However, the body cannot tolerate methanol (CH3OH). When methanol is ingested, ADH acts on it, breaking it down to formaldehyde, which is toxic to the human body. Emergency medical treatment for methanol poisoning includes intravenous injection of ethanol. Which statement provides the simplest, most likely explanation for how ethanol acts to prevent harm from methanol ingestion?

Ethanol acts as a competitive inhibitor of methanol to decrease the rate of methanol oxidation by ADH.

Which of these describes a catabolic pathway?

Breaks down complex molecules and releases energy

True/False: The cell never uses the product of a reaction for more than one pathway, every biochemical pathway has unique products.

False

True/False: If the reactants of a chemical reaction have 4.5 x 105 J of free energy and the products have 9.6 x 105 J of free energy, the reaction will be spontaneous.

False

Many of the compounds in cells have more free energy than the free energy of the reactants from which they are made. For example, glucose has more energy than the C02 and water from which it is made. Which of the following best explains how this can be?

Cells use energy inputs to widen the scale of the system.

Which of the following best summarizes how membrane lipids and many proteins spontaneously form ordered, predictable structures in aqueous solutions?