Chemical Bonding Lecture Flashcards
How much energy required to break covalent bonds?
50-100 kcal/mole
Describe the stability of covalent bonds
Quite stable under physiological conditions
How much energy required to break non-covalent bonds?
5 kcal/mole
Describe stability of non-covalent bonds
Break quite easily under physiological conditions but structures held by lots of cooperating non-covalent bonds could be very stable
Non-covalent bonds determine what 2 things?
- How molecules interact with each other
- Shape of large covalently bonded molecules (proteins, nucleic acids)
What does the strength of H bonds depend on?
Distance and orientation
e.g. maximum strength when three atoms in a straight line
What does the strength in electrostatic bonds depend on?
Distance, not orientation
Non-polar surfaces do not attract each other. They are…
Pushed together by the solvent
The strength of a hydrophobic “bond” between 2 non-polar surfaces equals…
The strength of additional water-water H bonds that form when nonpolar surfaces are removed from contact with water molecules
List the bonds in descending order of strength
Covalent > Hydrogen > Electrostatic > Hydrophobic > Van der Waals (0.5 kcal/mole)
An acid is…
A proton donor
A base is…
A proton acceptor
Dissociation of an acid always produces what?
A conjugate base
Protonation of a base always produces what?
A conjugate acid
Strong acids dissociate completely or incompletely?
Completely (equilibrium is very far right) e.g. inorganic acids like HCl, H2SO4
Weak acids and bases…
Exist in equilibrium with their conjugate species. Carboxylic acids are weak acids, amines are weak bases
[H+] changes __-fold when pH changes by 1 unit
10-fold
In the oral cavity, [H+] directly affects what?
The balance of mineralization vs. demineralization of the dental enamel
What is Ka a measure of?
The position of the equilibrium
What is the Ka eqn?
Ka = [H+][A]/[HA]
Ka is the H+ concentration at which exactly _____ of A is protonated
Ka is the H+ concentration at which exactly half of A is protonated, i.e. when [H+] = Ka, [A] = [HA]
Ka = [H+][A]/[HA]
What 2 things does the Henderson Hasselbalch Eqn tell you?
- The fraction of A that is protonated, if you know its pKa and the pH
- The pH, if you know pKa and [A]/[HA] ratio of a buffer
How does a buffer work?
It reacts with either added H+ or OH- to get rid of some of the added H+/OH- in order to decrease the pH change
What buffering reaction gets rid of added H+?
A + H+ –><– AH
What buffering reaction gets rid of added -OH?
AH + -OH –><– A + H2O
Because a buffer reaction is an equilibrium reaction, is all of the added H+ or -OH removed?
No
Buffers work well when the pH is near what?
Their pKa
What is the most important physiological buffer?
Bicarbonate (HCO3-)
Where is gaseous CO2 from lungs and tissues dissolved?
Blood plasma
CO2 (g) –><– CO2 (d)
CO2 (d) + H2O –><– H2CO3 (catalyzed by carbonic anhydrase)
H2CO3 –><– H+ + HCO3-
Give the eqn and equilibrium constant for the ionization of H2CO3 in equilibrium with dissolved CO2
Koverall = [H+][HCO3-]/[CO2(d)]
Koverall = 4.91 x 10^-7, pK = 6.31
IF the pH of blood (7.4) is more than 1 pH unit away from bicarbonate’s pK, why is the bicarbonate system an effective buffer?
Even though [CO2(d)] is about 10% of [HCO3-], the bicarbonate buffer system is an OPEN system.
So there is natural presence of CO2 gas at pp 40 mm Hg in lungs and the equilibrium
CO2 (g) –><– CO2 (d)
maintains the CO2 (d) at fairly constant level
Metabolism generates ____ in the body
acidity
The bicarbonate buffer system allows the body to convert __ from metabolic acids into a ______ that can be exhaled from the lungs
The bicarbonate buffer system allows the body to convert H+ from metabolic acids into a gaseous form (CO2) that can be exhaled from the lungs. Doing so, it evaporates the acidity
List the 6 non-polar aliphatic amino acids
Glycine
Alanine
Proline
Valine
Leucine
Isoleucine
List the properties of non-polar amino acids
Have methyl/ene side chains that cannot H bond
Avoid water and are found in center of protein structures
Abundant components of protein
Glycine has only H atom side chain
Alanine only has methyl group side chain
List the 4 polar uncharged amino acids
Asparagine
Glutamine
Serine
Threonine
List the properties of the polar uncharged amino acids
Interact well with water through H bonding
Often found at surface of proteins
List the 3 aromatic amino acids
Phenylalanine
Tyrosine
Tryptophan
Lis the properties of the aromatic amino acids
Usually hydrophobic
Often buried within protein structures
Their side chains sometimes stack with nucleobases in active sites
Tyr and Trp can H bond and aren’t always buried
Trp is least abundant AA in protein
List the 2 sulfur-containing amino acids
Methionine
Cysteine
List the properties of the sulfur-containing amino acids
Sulfur in Cys reactive to oxidation and can form disulfide bridges
Extracellular proteins like trypsin, insulin, & blood clotting factors held together in part by disulfides
List the 2 negative acidic charged amino acids
Aspartate
Glutamate
List the 3 positive basic charged amino acids
Arginine
Lysine
Histidine
The charged AAs have side chains that are _____ or _____
acidic; basic
What is Asp and Glu’s pKa roughly at?
4
Which positively charged basic AA has a high pKa?
Arginine
What is the pKa of Lys?
9-10
What is the pKa of His?
6
List the properties of the charged AAs
Often protrude at surface of proteins
Often found making electrostatic interactions with other residues
What is a Zwitterion?
A molecule with a positively charged amino group and a negatively charged carboxyl group
What is the isoelectric point (pI)?
pH at which a molecule has no net charge. It’s the average of the pK’s of the amino and carboxyl groups.
Which amino acids predominate in their protonated form at physiological pH of 7.4?
Cysteine
Tyrosine
Lysine
Arginine
Which amino acids predominate in their deprotonated form at physiological pH of 7.4?
Aspartate
Glutamate
Histidine
Due to electronic resonance, peptide bonds have partial double bond character, which makes them…
Planar and rigid
Insulin is made as a precursor of how many AAs?
80
Insulin’s precursor is cleaved how many times to make its 2-chain active form?
4
How many disulfides in insulin?
3 (6 original cysteines, now 3 cysteines)
What is the most stable protein structure if it needs to be in solution?
Secondary
What reaction happens in secondary structure?
Carboxyl oxygen accepts H from peptide hydrogen 4 residues later in the sequence. This stabilizes the alpha helix in which R groups protrude at regular intervals.
Helices can be…
amphipathic
Beta strands can form which bonds?
Regular H bonds with neighbouring beta strands to make beta sheets in which adjacent R groups can also interact. Beta turns can be formed with stabilizing H bonds
Which polypeptides can form triple helices?
Polypeptides with glycine residues at every 3rd position because H of alpha carbon sticks into middle of triple helix and no other AA R group can fit
Why does collagen form a cable-like structure of great strength?
Bc collagen chains associate into triple helixes
What kind of bonds hold primary structure together?
Covalent bonds
What kinds of bonds hold together the secondary, tertiary, and quaternary structures of folded proteins inside the cell?
Noncovalent bonds
Secondary structures are held together by what bonds between C=O and N-H atoms of peptide bonds?
H bonds
What determines which segments of a polypeptide chain can form stable alpha helix or beta sheet?
The side chains of the amino acids
Hemoglobin is composed of…
2 alpha and 2 beta subunits
LDH has…
4 copies of a single subunit type
Globins are largely what?
Alpha-helical
Why are globins a bit unusual?
They have all helix connected by turns
What don’t globins have?
beta structure
What structures does myoglobin not have?
Quaternary
What structure does hemoglobin not have?
It has all structures
We could say that the folded structure of protein is encoded in the ____ _____ ______
amino acid sequence
Why is the quaternary structure important?
It facilitates more complex protein behaviour
It is the basis of many important anatomical structures
The single subunit of myoglobin binds oxygen ____ _____, in a simple ______ ______ reaction that depends on the _____ _____ ______
The single subunit of myoglobin binds oxygen fairly strongly, in a simple reversible equilibrium reaction that depends on the free oxygen concentration
How does hemoglobin’s quaternary structure benefit it?
4 subunits bind and release O2 in a concerted fashion, giving a sigmoid binding curve with a threshhold of binding
When Keq is very large, a _____ amount of reactant is present at equilibrium
tiny
Sometimes say reaction is “irreversible”
What 2 things do Keq and G tell us?
- Relative proportion of reactants and products that will be present at equilibrium
- How much useful work can be obtained from a reaction, under standard conditions when [products] = [reactants] = 1 M
If Keq > 1 (G < 0), equilibrium favors ______, and the reaction will ______ energy
products; yield
G = 0 means that…
The reaction is at equilibrium
If Keq <1 (G > 0), equilibrium favors _______, and the reaction will _____ energy
reactants; absorb
Keq and G tell us nothing about what?
How fast a reaction will occur
Kinetically favoured means…
it forms the fastest in a reaction
Thermodynamically favoured means…
it is the most stable
ATP is thermodynamically ______
unstable
ATP is kinetically ______
Stable
Catalysts…
lower energy of activation and increase the rate at which reaction goes to equilibrium
Keq and G depend on what?
Initial and final states
Are Keq and G altered by presence of a catalyst?
No
An enzyme increases the rates of the forward and reverse reactions….
by exactly the same factor
Enzyme kinetics are…
a quantitative description of enzyme activity as a function of substrate conc
In uncatalyzed reactions, the reaction rate depends on what?
The conc of reactants in a simple linear fashion (law of mass action)
In catalyzed rxns, the reaction rate levels out when?
At high substrate conc
Vmax is a measure of what?
The max capacity of the enzyme
What does Vmax depend on?
How much of enzyme is present
Km is a measure of what?
The affinity of the enzyme for the substrate. It tells us how a given amount of that enzyme will respond to changes in substrate conc
What is Km independent of?
Amount of enzyme present
Km is the substrate conc at which the activity of the enzyme is ___ ___ ___
half of Vmax (half-maximal)
Removal of the inhibitor results in ____ ____ of enzyme activity
rapid recovery
Enzyme inhibition usually refers to what?
Reversible inhibition
Give 2 examples of reversible enzyme inhibitors
Physiological enzyme inhibitors; many drugs
Enzyme inactivation refers to what?
Irreversible effects
Give 2 examples of irreversible inactivators
Some drugs like aspirin and many toxic substances (esp toxic metals)
Name 2 reversible inhibitors
Competitive and non-competitive inhibitors
With competitive inhibitors, inhibition can be overcome with what?
High [S]
What are an important class of competitive inhibitors?
Enzymatic reaction products
Can non-competitive inhibitors be overcome with high [S]?
No
What happens to the Vmax and Km with competitive inhibition?
Vmax stays the same
Km increases
What happens to the Vmax and Km with non-competitive inhibition?
Vmax decreases
Km stays the same
Aspirin is a suicide substrate for…
Cyclooxygenase
Acetoaminophen and ibuprofen are _____ inhibitors of cyclooxygenase
Reversible
Bind but don’t react at active site
Lead and mercury react with which groups?
-SH groups
Lead and mercury act as _____ ____ of many enzymes
irreversible inactivators
Mercury is a controversial component of _____ ____
dental amalgam
Mercury is extremely ___ ___ in ____. The rate of release is _____ ____.
Mercury is extremely tightly bound in amalgam. The rate of release is extremely slow.
