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Definition of Biochem
Study of life at a molecular level and the application of the principles of chemistry to explain biology
What are the 4 Major classes of biomolecules?
1. Proteins
2. Nucleic Acids
3. Lipids
4. Carbohydrates
Does the considerable difference in all living life mean they are different molecularly?
All organisms are remarkably uniform at a molecular level
What do all organisms use?
Common building blocks to create common biomolecules (nucleic acids, proteins, polysaccharides, and lipids)
4 Different Foundations of Life
1. Chemical
2. Energy
3. Genetic
4. Evolutionary
What are the four main elements that compose around 98% of most organisms?
Carbon
Oxygen
Hydrogen
Nitrogen
What are all known life forms based from?
Carbon
How many people could naturally occuring nitrogen in the world feed?
4 Billion
Who was able to get "bread from air" using nitrogen from the air as fertilizer
Fritz Haber
How much is a human worth?
-Chemically only less than a dollar
-Looking at the chemical components like tissues, organs, and biomolecules have an estimated value of $45 000 000
What is the next best candidate as the chemical foundation of life?
Silicon
Why does Carbon work better than Silicon?
-C-C bonds are stronger than S-S bonds
-C-C bonds release more energy on combustion than S-S bonds
-Combustion of C-C bonds are soluble and remain active in biosphere
What do functional groups determine?
The collective properties of functional groups determine the structure, function, and propeties of the biomolecule
What does understanding the structure-function relationship of biomolecules help predict?
Molecular function, complex biology, and rational development of treatments
Conformation
Flexible spatial arrangment of atoms within a molecule (changeable without breaking bonds)
Configuration
Fixed spatial arrangement of atoms with a molecule (Not changeable unless covalent bond is broken)
-Conferredby either double bonds or chiral centers
Geometric Isomers
(Cis-trans) Same chemical formula but different configuration of groups attached to a non-rotating double bond
Cis
Same side of double bond
Trans
Opposite side of double bond
Chiral Carbon
4 different substituents attach to a single carbon that can be arranged differently in space creating 2 stereoisomers
Construction
Biomolecules are often constructed from one stereoisomer
Interactions
Interactions between biomolecules, as well as between biomolecules and small molecules, are stereospecific
Simplicity
Simple, conserved reactions for synthesis and degradation
What do chemical synthesis of molecules with asymmettric carbons create?
A mixture of all chiral forms
-Each form can have different effects
4 Major Classes of Biomolecules
1. Protein
2. Carbohydrates
3. Nucleic Acids
4. Lipids
The Case of Thalidomide
Ex. chemical synthesis of molecules created a different mix of chiral forms
-One helped with nausea and the other caused birth defects
-Dr. Francis Kelsey a reviewer from the FDA denied the drug
3 Biological Polymers
1. Simplicity- Simple, conserved reactions for synthesis and degration
2. Recycling-Biomolecules can be digested back to component building blocks which are reusable
3. Diversity- Molecules of incredible complexity can be generated
Proteins
-Linear polymers of aminoacids
-20 different amino acids
-Amino acids link into chains that create complex patterns with distinctly different purposes (proteins)
Polysaccharides
-Carbohydrate
-Monosaccharides that are linked together to form a polymer
-Serve biological roles like structure, energy storage, and cellular recognition
Nucleic Acids
-Linear polymers of nucleotide building blocks
-5 "building blocks"
Lipids
Lipids are aggregates of "building blocks"
-Serve in energy storage, formation of membranes, and signalling
Prokaryotes
-Small single cell organism
-Growth is rapid allowing quick adaptation
-Single compartment , the nucleoid
Eukaryotes
Large complex cells
-Make up multi-cellular organisms
-Contain organelles
Around how many prokaryotic and eukaryotic cells are in your body?
30 trillion eukaryotic cells and 100 trillion prokaryotic cells
What does bacteria in the gut do?
Bacteria in the gut helps digest foo and maintain a functional immune system
What does Microflora in the gut do?
Impacts health
-Depression, anxiety, obesity, and intelligence
"some people are calling the gut the second brain" - Scott Napper
Are bacteria friends?
Yes, bacteria are my friends
Vitro
Studies the behaviour of molecules outside the context of the cell and or organism (in glass)
Vivo
Studies that occur within the cell or organism (in the living)
First Law of Thermodynamics
Energy can be transferred and transformed, but it cannot be created or destroyed.
Second Law of Thermodynamics
Nature has a tendency toward greater total entropy of the universe as it continually increases
Gibbs Free Energy Theory
Energy changes during chemical reactions
-Free energy can be defind in terms of:
Enthalpy- # and kinds of bonds Entropy- Degree of randomness Temperature-In Kelvin
G = H - TS
G > 0 = endergonic
G < 0 = exergonic (spontaneous)
G = 0 = equilibrium
Enthalpy (H)
Reflects the number and kinds of bonds
Entropy (S)
The degree of randomness
Temperature
Degrees Kelvin
Energy Coupling
Cells thermodynamically drive unfavourable ractions by couply endergonic(energy requiring) and exergonic reactions (energy releasing)
ATP in Metabolism
-Serves as an energy currency
-ATP serves as the link between catabolic reactions and anabolic reactions
Steps of Replication
1. DNA undergoes transcription
2. RNA undergoes translation
3. Results in a protein
Nucleotide Sequence
Dictates the sequence of amino acids added into a protein
What does amino acid sequence do?
Dictates proteins structure
Water
-Abundant molecule in living organisms
-Both passive and active roles
Passive Role of Water
Structure of biomolecules forms in response to interactions with water
Active Role of Water
Water is a participant in many biochemical reactions
What gives water a permanent dipole?
Oxygen is more electronegative than hydrogen
-Forms electrostatic interactions
-Forms hydrogen bonds
What can random changes in genotypes do?
Can change the phenotype that can lead to an advantage or disadvantage for the organism
(Evolution)
What is the basic unit of DNA?
Two complimentary strands
-Each strand is a linear polymer of 4 types of building blocks
What is the most abundant molecule in living organisms?
Water
Passive Water Molecule
Structure of biomolecules forms in response to interaction with water
Active Water Molecule
Water is a participant in biochemical reactions
Alternate liquids that could support life
Ammonia and Formamide
What does the dipole of a water molecule influence?
-Forms electrostatic interactions with charged molecules
-Forms hydrogen bonds
What can both Oxygens and nitrogens serve as?
Hydrogen bond donors and acceptors
How strong is a hydrogen bond relative to a covalent bond?
5% the strength of a covalent bond
What does the strength of a hydrogen bond depend on?
its geometry
-anti-parallel beta sheets more stable than parallel
How many hydrogen bonds can a water molecule form?
4- 2 as a donor and 2 as an acceptor
In water water is the average hydrogen bond per molecule?
3.4 "flickering cluster"
What can influence the properties of water?
Great internal cohesion between water molecules and hydrogen bonds
Heat Vaporization
The amount of heat required to vaporize a liquid at its boiling point
Specific Heat Capacity
The amount of heat required to raise the temp of a substance by one degree
Unusual Properties of Water
When in solid form the arrangement of ice has a lower density than liquid water making ice float
-Water has a higher melting, and boiling point
Polywater
Form of water with higher boiling point, lower freezing point, and higher viscosity
-Fear it could be weaponized
Electrostatic Interactions
Molecules interact with charged solutes through formation of payers of hydration
-Small size and permanent dipole makes water great in interacting both positively and negatively charged ions
-Water shields charged groups and diminishes strength
Molecule Solubility in water
Hydrophilic = molecules polar
Hydrophobic = molecules non-polar
Amphipathic = both hydrophobic and hydrophilic portions (most molecules)
What do non-covalent interactions enable?
-Transient, dynamic interactions
-Flexibility, formation of structure and function
-Binding of reactants to enzymes
-Recognition between molecules
Non-covalent Interactions Include
1. Hydrogen bonds
2. Ionic interactions
3. Hydrophobic interactions
4. Van Der Waals interactions
What are Hydrogen bonds critical for?
Specificity of biomolecular interactions not for the formation of biomulecular structures
Van Der Waals Forces
Interaction between permanent and induced dipoles (short range, low magnitude interactions
-When two surfaces come together a large # of atoms are brought into VDW contact
-Abundant in the core of folded proteins
Hydrophobic Effect
Drive to have polar groups interactin with water and non-polar regions shielded away from it
-Proteins fold to make this happen
What does the folding of a polypeptide do?
Decreases entropy of polypeptide but increases the entropy of the associated water
What is the ion product of water?
Kw
ph = ?
the difference of 1 pH unit equals a 10-fold difference in H+
Which acids and bases dissociate completely in water?
Strong acids and bases
Amphipathic Molecules
Hydrophilic regions interact with water but hydrophobic regions cluster together presenting the smallest surface to water
Which acids and bases do not dissociate completely in water?
Weak acids and bases
-Dissociation can be quantified
pKa =?
-log Ka
What happens when pH = pKa
Solution is best able to resist changes in pH
Stronge acid = ____pKa
Low
Peptide bonds
Covalent linkages between carboxyl group of one AA and amino group of another
How do peptide bonds form?
Condensationg reaction involving generation of a water molecule
Repeating pattern of Polypeptide main chain
NCCNCC
Primary Structure
Linear sequence of Amino Acids
-Info for specifying correct folding contained here
Secondary Structure
Localized interactions within a polypeptide
-Maintained by hydrogen bonds between main chain amide and carbonyl groups
-Peptide bond has both hydrogen bond acceptors and donors
-Is favoured
Tertiary Structure
Final folding pattern of a single polypeptide
-Amino Acid sequence determines tertiary structure
Quaternary Structure
Folding pattern when multiple polypeptides are involved
-Help facilitate unique dynamic combinations of structure/function
Amino Acids
The building blocks of proteins
Phi and Psi
Can range from -180 to 180
Simplicity of Chemistry
One reaction for polymerization the other for degradation
Recycling
Biomolecules can be digested into reusable building blocks
Henserson-Hasselbalch Equation
1. Relationship of the pH of the solution
2. The pKa of the weak acid
3. Relative concentrations of the weak acid and conjugate base
Diversity
Potential for vast # of molecules of different lengths and sequences