Lecture 1 & 2 Flashcards
Current biochemical generalization regarding living things:
1) Life requires ____, viruses are _____
2) Biochemical reactions require ____
3) The information of life is transmitted in the ____
4) The Central Dogma of life information flow is ___
1) Life requires LIFE, viruses are NOT LIVING
2) Biochemical reactions require CATALYSTS
3) The information of life is transmitted in the GENOME
4) The Central Dogma of life information flow is DNA -> RNA -> PROTEIN
Gibb’s Free Energy formula:
∆G = ∆H - T∆S
What is Gibb’s Free Energy defined in terms of?
defined in terms of Enthalpy (heat) and Entropy (disorder) at a given temperature (kelvin)
∆G<0 =
∆G<0 = spontaneous, reaction releases energy
∆G>0 =
∆G>0 = non spontaneous, reaction absorbs energy
∆G=0 =
∆G=0 = equilibrium, no energy change
What does spontaneous say about the rate?
NOTHING
If ∆H is - and ∆S is +, what will the reaction look like?
the reaction is both enthalpically favored (exothermic) and entropically favored
it is spontaneous (exergonic) at all temperatures
If ∆H is - and ∆S is -, what will the reaction look like?
the reaction is enthalpically favored BUT entropically opposed
it is spontaneous only at temperatures below T = ∆H/∆S
If ∆H is + and ∆S is +, what will the reaction look like?
the reaction is enthalpically opposed (endothermic) BUT entropically favored
it is spontaneous only at temperatures above T = ∆H/∆S
If ∆H is + and ∆S is -, what will the reaction look like?
the reaction is both enthalpically and entropically opposed
it is non spontaneous (endergonic) at all temperatures
Some of the most important reactions in biochemistry are:
non spontaneous, they require energy
How do you make non spontaneous reactions go?
- couple the non spontaneous reaction with a spontaneous reaction that produces more energy than needed to make the non spontaneous reaction go
- ATP the cell’s energy source reaction releases 30.5 kg/mol
- energy release from ATP
In the reaction of converting ADP back to ATP, the reaction is powered by what?
powered by a proton gradient where the body is never at equilibrium
(at equilibrium, there are no gradients)
What happens at equilibrium?
reactions near equilibrium can operate in either direction
What is Le Chatelier’s Principle?
a chemical system, once at equilibrium will respond to a stress or change in the environment to reduce the stress
Exothermic
products have lower energy
Endothermic
products have higher energy
At equilibrium-
-the concentrations of all species remain constant over time
-both forward and reverse reactions occur BUT at the SAME RATE
For something to be at equilibrium, what is the rule of products and reactants and their rate?
there is no rule that products = reactants BUT rather that the rate of the forward and reverse reactions are equal
We are carbon-based life forms, what are some things that contain a majority of carbon atoms?
proteins
nucleic acids
carbohydrates
lipids
PROTEINS
Atoms:
Building Blocks:
Forms polymers? type of blood:
Intra-molecular interactions:
Functional role in cells:
Atoms: C, H, N, O, S
Building Blocks: Amino Acids
Forms polymers? type of bond: Yes, Peptide bonds
Intra-molecular interactions: Covalent (S-S), H-bonds, charge based, van Der Waal’s
Functional role in cells: Enzymes, structural proteins, sensors, receptors, etc.
NUCLEIC ACID
Atoms:
Building Blocks:
Forms polymers? type of blood:
Intra-molecular interactions:
Functional role in cells:
Atoms: C, H, O, P, N
Building Blocks: Nucleotides
Forms polymers? type of blond: Yes, phosphodiester bonds
Intra-molecular interactions: H-bonds, stacking interactions
Functional role in cells: Storage of genetic information, enzymes, ribosomes
CARBOHYDRATES
Atoms:
Building Blocks:
Forms polymers? type of blood:
Intra-molecular interactions:
Functional role in cells:
Atoms: C, H, O, N
Building Blocks: Simple sugars
Forms polymers? type of blond: Yes, glycosidic linkages - of various types
Intra-molecular interactions: H-bonds
Functional role in cells: storage of energy, structural, recognition, interactions
Lipids
Atoms:
Building Blocks:
Forms polymers? type of blood:
Intra-molecular interactions:
Functional role in cells:
Atoms: C, H, O
Building Blocks: Fatty acids, glycerol
Forms polymers? type of blood: No, forms various di-, tri-, glycerides
Intra-molecular interactions: Van Der Waal’s
Functional role in cells: Membranes, signaling, energy storage, small molecule hormones
What are the four important classes of biomolecules?
1) proteins (amazing diverse polymers
- hemoglobin
2) carbohydrates
- glucose
3) lipids
4) nucleic acids
DNA provides what for proteins?
DNA provides the protein template
What are proteins a series of and what can they do?
Proteins are a series of LINKED AMINO ACIDS that can FOLD into functional structures
Lysozyme
-enzyme
-part of the innate immune system
-protects infection from Gram-positive bacteria (Salmonella, E. coli, and Pseudomonas)
-found in tears
What are the four important carbohydrates?
glucose
ribose
deoxyribose
cellulose
Which important carbohydrate is this?
Glucose
Which important carbohydrate is this?
Ribose
Which important carbohydrate is this?
Deoxyribose
Which important carbohydrate is this?
Cellulose
What is the blue, and what is the yellow part of this lipid?
Blue: polar head, hydrophilic
Yellow: non polar tail, hydrophobic
What do membrane proteins do?
interact with the environment
How do membrane proteins interact with the environment?
ion/water/small molecule transport
-cell signaling, cytokines, hormones, receptors
A DNA strand has direction, the 5’ and 3’ ends have what different groups?
5’ end: terminal phosphate group
3’ end: terminal hydroxyl group
What cells contain
- no nucleus
-intracellular membrane
-usually unicellular
prokaryotic cells
What kind of model organisms do biochemists focus on for their studies?
prokaryote cells (escherichia coli)
Examples of eukaryote cells
humans
mice
rats
yeast
arabidopsis
drosophila (fruit fly)
Which cell contains membrane-bound organelles?
eukaryotic cell
Examples of membrane-bound organelles in a eukaryotic cell:
nucleus
ER
Golgi
mitochondria
lysosomes
peroxisomes
chloroplasts
Cells are crowded. What do crowding effects do to diffusion rates?
crowding effects REDUCE diffusion rates in the cell
Proteins are gene products created by what?
Proteins are gene products created by the ribosome by translating mRNA
What are considered the “cell’s workhorses”?
Proteins
A large, linear molecule made up of repeating units.
Polymer
Proteins are amazing _____.
Proteins are amazing HETEROPOLYMERS (different amino acids)
Proteins are made of how many amino acids?
20 amino acids
Mulder derived the chemical formula of an animal substance (protein). He used ___ ____ to produce _____ the building blocks of proteins (we know them today as amino acids).
Mulder derived the chemical formula of an animal substance (protein). He used ACID HYDROLYSIS to produce “GRUNDSTOFF” the building blocks of proteins (we know them today as amino acids).
What are proteins made by and what does it contain?
made by the ribosome which contains amino acids and RNA
What are proteins a chain of?
amino acids corresponding the gene’s base-pair sequence
What does the sequence of amino acids in proteins determine?
determines how the proteins are folded and their function
The peptide bond is a ___ structure.
The peptide bond is a PLANAR STRUCTURE.
Why are these two structures planar structures?
-the N and carbonyl C are sp2 hybridized
-both can resonate yielding the planar structure
-peptide plan spans the chain between two alpha carbons
What are the six atoms in the peptide plane?
Cx3 - carbon
N - nitrogen
O -oxygen
H - hydrogen
What does the function of a protein depend on?
depends on its structure
Where is the peptide plane?
-look for sp2 atoms
-look for N and C double bonded to O
What does the sequence of amino acids direct?
directs the peptide chain to spontaneously ‘fold’ into the “native-lowest energy” structure of the protein
What are the mysterious forces that drive protein folding?
1) electrostatic (charge interactions)
2) hydrophobic effects
- oil and water don’t mix
What are the electrostatic (charge interactions)?
-salt bridges (pH dependent) & ionic bonds
-hydrogen bonds
-van der Walls interactions
How is a hydrogen bond formed?
by sharing a hydrogen between two dipoles
(due to an asymmetric distribution of electrons between atoms with different electronegativities (H<C<N<O)
Are hydrogen bonds pH dependent?
NO not pH dependent
Hydrogen donor
the atom with a higher affinity for, and is covalently attached to the H
-has a partial positive charge
What are common donor atoms?
O
N
S
ALMOST NEVER C
Hydrogen acceptor
an atom that contributes a lone pair of electrons to the H- bond
-has a partial negative charge
What is formed by sharing a hydrogen UNEQUALLY between two dipoles?
hydrogen bond
What are dipoles?
molecular dipoles are due to an asymmetric distribution of atoms with different electronegativities
(H<C<N<O)
Rules of hydrogen bond strength:
1) the H-A distance (closer =stronger)
2) the D-H—–A angle (180 degrees is the strongest)
van der Waals interaction
1-the electron shell represents the electron density function of the atom
-random fluctuations of the electrons can produce a dipole
Induced Dipole in a VDW Contact
the orbitals of two molecules will establish resonance at close distances and behave as weak dipoles
Non-covalent interactions contributions to folding and stability? (what are the 3 and their kJ/mol)
1) Salt Bridge -20 to -40 kJ/mol
2) H-Bond -2 to -20 kJ/mol
3) VDW -0.4 to -4 kJ/mol
How does water interact with proteins?
via Dipole-charge interactions
When water is interacting with proteins, what does it compete with?
water competes for intrapeptide H bonds and salt bridges
(desolvation of polar or charged groups costs energy)
The energetic cost of desolvation implies what?
implies that- intrapeptide H-bonds and Salt Bridges contribute LITTLE to the stability of a folded protein
Why is delta G of peptide H-bond/salt bridge formation close to zero?
1) competition with water
2) often the intrapeptide bond geometry is less than ideal
What must be done first to form an inter peptide H-bond?
you must first break water H-bonds
The hydrophobic effect
Liquid water averages: 3.4 H-bonds
Ice averages : 4 H-bonds
Ice H-bonds are stronger despite the loss in entropy. How does the “hydrophobic effect explain this?
Stronger H-bonds because water is a great DONOR when it is being ‘protonated’ (increases partial +)
Stronger H-bonds because water is a great acceptor when it is being ‘deprotonated’ (increases partial -)
What is surface tension due to?
an ice-like ordering of water at the surface
Solvation of hydrophobics
-unfavorable due to the increased order (lower entropy) of the water molecules
Solvation energy
-proportional to the volume of the clathrate (large clathrate = more order)
What is the hydrophobic effect (explained)?
-driven by the entropy of water
-is proportional to the decrease in surface area of the ordered water
How do non-covalent interactions contribute to folding and stability?
H-bonds and salt-bridges provide specificity, and are a necessary consequence of folding
they have a SMALL contribution to stability
What drives protein folding?
electrostatic (charge interactions)
-salt bridges & ionic bonds (20-40 kJ/mol
-H-bonds (2-20 kJ/mol)
-van der Walls interactions (0.4-4 kJ/mol)
-hydrophobic effects (3-10 kJ/mol)
Why is a micelle our first model for protein folding and structure?
1) hydrophobic interior and hydrophilic surface
2) it is self-forming
How do amino acids pack together?
pack together like puzzle pieces to fill the interior of a protein
What are the structures of micelles and soluble proteins due to?
due to the hydrophobic effects
What is the pH scale?
14 = pH + pOH
What is the Henderson-Hasselbalch Equation?
What is a buffer?
a weak acid or base, used to maintain a specific pH by absorbing or releasing protons according to the Le Chatelier’s principle
What determines the buffering range?
pKa
What does pKa tell us?
tells how strongly the acid/base wants the proton
at pH below the pKa what happens?
the group will be PROTONATED (HA)
-KEEPS THE PROTON
at pH above the pKa what happens?
the group will be DEPROTONATED (A-)
-LOSES PROTON
What is the pKa of water?
15.7
What does the pKa of water really mean?
water wants to REALLY REALLY keep its proton (pH is below pKa)
-water rarely dissociates to donate a proton (SUPER RARE)
What does pKa predict?
predicts the leaving group
How does pKa predict the leaving group?
leaving group will be the conjugate acid with the LOWEST pKa
What do you need to know about pKa?
-determines buffering range
-tells how strongly the acid/base wants the proton
-predicts what the leaving group will be
- AA ionizable groups will be positive if pH<pKa
-AA ionizable groups will be negative if pH>pKa
How do we maintain our physiological pH?
the pH of the blood is regulated primarily by the CO2 -carbonic acid - bicarbonate buffer system
What is the pH of Human blood plasma?
about 7.4
What is the CO2-carbonic acid-bicarbonate buffer system?
at low pH (tissue) excess acid (H30+) in the body is neutralized by HCO3-
-equilibrium shifts left
at high pH (lungs) the excess base (OH-) reacts with the carbonic acid (H2CO3)
-equilibrium shifts right
How effective is the CO2-bicarbonate buffering system?
highly effective
