01 Chemistry of Life Flashcards
List the four requirements of life on Earth and how these ideas were backed up experimentally.
- Simple gaseous molecules eg. NH3, CH4, H2
- Liquid water - from condensation as the earth cooled, new molecules formed in water
- A reducing environment - low oxygen environment is supportive of bond formation of C, N, O and H
- Electrical discharges - from lightning, volcanic activity provides kinetic energy for molecules to collide and form bonds.
Miller-Urey experiment - replicated primordial earth and showed that amino acids could from from this envrionment
What is the bond between amino acids called? What do they form?
peptide bond or amide bond. Polypeptide or proteins
What is the bond between nucleotides called? What do they form?
phosphodiester bond. Polynucleotides or nucleic acids (DNA or RNA)
What is the bond between saccharides called? What do they form?
glycosidic linkages. polysaccharide/carbohydrates
Name the 7 different types of interactions
charge-charge, charge-dipole, charge-inducted dipole, dipole-dipole, dipole induced dipole, Dispersion (van der waals) and Hydrogen bonds
Why do molecules use weak interactions internally (intramolecular)? Give an example
- For molecules to be only just stable enough so that they can function properly but also be recycled (degradation, proteolysis) easily.
eg. proteins are only just stable (Gibbs is -50 kJ/mol - equivalent to two H bonds)
(if proteins were held together by covalent bonds rather than weak vdW and H-bonds, it would take a lot of energy within the cell to degrade and recycle them - wasting cellular energy)
Why do molecules use weak interaction to interact with other molecules (intermolecular)? Give an example
- receptor binding. The binding needs to be strong enough to cause some effect but not too strong such that the molecule cannot come off the receptor when signalling needs to stop. (same goes for enzymes)
eg. glucagon on glucagon receptor
How much distance are DNA base pairs from each other when stacked?
0.34 nm or 3.4 Å
What is the closest distance atoms can approach each other without repulsing each other?
The closest approach attracting atoms can make is the sum of their vdW radii.
How do hydrogen bonds differ from vdW interactions in terms of radii? What does this tell us about the nature of a H-bond?
a hydrogen bond is shorter than the sum of the vdW radii. Because the two atoms approach more closely than the vdW radii should allow without repulsing each other, we conclude that a hydrogen bond is partially covalent in character.
How does water interact with Ionic Compounds?
Ionic compounds dissolve in water and the ions separate by coordinated water molecules. The positive charged ion is surrounded by hydration shells where the oxygen is pointing towards them. The negatively charged ion has the positively charged H pointing towards it in a hydration shell.
How does water interact with Polar Molecules?
Water molecules can form hydrogen bonds and other interactions with polar molecules as polar molecules have permanent dipoles. A molecule can make as many H-bonds as there are lone pairs on the atom.
NOF - H can form hydrogen bonds
How does water interact with Hydrophobic molecules?
rigid cage like structure similar to that of ice around the molecule,
water molecules cannot freely rotate and form hydrogen bonds as readily as bulk fluid water.
Non polar molecules are only sparingly soluble in water.
They also disrupt the high entropy state of bulk, liquid water
How do amphipathic molecules behave in aqueous solution?
Their non polar parts will cluster together away from water, leaving the polar parts to form hydrogen bonds or other favourable weak interactions with the water molecules. (micelle)
Why is the lipid bilayer essential for life on earth?
- it is relatively impermeable - barrier controlling which molecules can cross form one side to the other
- Compartmentalisation - this may be cells in an organism or organelles within cells. Keeping molecules separated in the right place (unique feature of life, v. important)
What properties of water make it such an important molecule in biology?
- small, polar and hydrogen (4) bonding potential
- liquid most of the time on Earth because of the size and extensive hydrogen bonding
- dissolves ionic and polar molecules
- drives amphipathic molecules like lipids to assemble into higher order structures like bilayers and vesicles. this is the hydrophobic effect in action
- driving force for protein folding. hydrophobic side chains dont interact favourably with water in unfolded protein, but in the folded protein these side chains are buried inside the protein and away from water. The water around folded proteins covered with hydrophilic side chains, is liquid and flowing and able to make lots of hydrogen bonds to the proteins and to other water molecules - high entropy and a favourable state. this is another example of the hydrophobic effect.
at pH < pKa side chain is found in the …
acid from, protonated
at pH = pKa side chain is found in the
equal amounts, 50:50 mixture, de-protonated and protonated
at pH > pKa base side chain is found in the …
base form, de-protonated
Multiple protein conformational states of an unfolded protein FAVOUR/DISFAVOUR folding? Explain.
Disfavour (entropy is high, favourable)
The formation of new weak interaction FAVOURS/DISFAVOURS folding? Explain.
Favours, hydrogen bonds, vdW are stable and favoured
The hydrophobic effect FAVOURS/DISFAVOURS folding? Explain.
Favours. water is restricted in its movement, and thus in a lower entropy state when it cannot rotate freely, folding of proteins buries hydrophobic chains inside - water can move and rotate freely around hydrophilic side chains - favourable.
Define the term “metamorphic” in terms of protein folding
metamorphic proteins are those with a single amino acid sequence that adopts multiple folded conformations under native conditions and interconverts reversibly between states. (alpha to beta vv)
Explain why the hydrophobic effect is so critical for protein folding
the main driving force for protein folding is minimisation of the solvent-exposed non-polar, hydrophobic surface area. the non-polar regions cluster as to shield themselves from contact with the polar/aqueous environment. –> causes proteins to fold
Does protein folding require energy? Explain
Yes. Going from an unfolded high entropy state to a folded low entropy state requires the input of energy as it is not favourable to be in the folded state.
Where does the energy for protein folding come from?
- formation of new weak interactions in protein folding releases energy - new hydrogen bonds and vdW interactions are favourable - lowers the energy of the system
- the hydrophobic effect - non polar hydrophobic molecules (side chains) in solution will come together
What is amyloid disease?
the build up of abnormal protein called amyloid
Describe how amyloid disease occurs in terms of protein folding and aggregation?
- a healthy protein unfolds and then forms a misfolded version of the protein now containing beta sheet structures.
- These proteins aggregate forming oligomers, amorphous aggregates and fibrils which now form intermolecular hydrogen bonds across the beta-sheet structures. The H-bonding is extensive and form massive sheet structures of millions of molecules
- The amorphous aggregates and fibrils are really low in energy so will not reform to the original healthy protein again and are very hard for cells to degrade.
What bond types dominate in diseased proteins? Explain the significance.
In the disease forms, intermolecular weak interactions start to dominate and make these structures stable.
(in normal proteins intramolecular interactions dominate)
What is molecular recognition?
refers to the specific interaction between two or more molecules through weak interactions and includes shape, size (length, radius, diameter) and feeling/WEAK INTERACTIONS.
What is an oxyanion hole? What is its significance?
A pocket in the active site of an enzyme that stabilises a reactive, unstable oxygen species (i.e. negative charge on a deprotonated oxygen or alkoxide)
It is crucial for the stabilisation of high-energy oxyanion intermediates or transition states through hydrogen bonding.
Which area of proteins forms interactions with other proteins?
Side chains NOT the amino or carboxyl terminals!!!
What are the three rules of folding that apply to proteins?
- Number of conformations/states unfolded vs. folded
- Formation of new weak interactions
- Hydrophobic effect
Describe how DNA follows the three rules of protein folding
- Number of conformations/states unfolded (many) vs folded (only one). - DNA folds up into a double helix with a change from high entropy (favoured)
to low entropy (not favoured). - Formation of new weak interactions-
DNA base-pairing (hydrogen bonding) and the DNA base stacking (vdW)
interactions found in the folded DNA. - Hydrophobic effect – non-polar DNA bases are hidden inside the helical
structure away from water. Hydrophilic and charged phosphates are on the outside of the DNA and will interact with water molecules or histone proteins in chromosomal packaging.
Define ionisable groups
Functional groups that act as proton-donor or proton acceptor influence the capacity for a molecule to act as an acid or base.
Define pka
describes the propensity of a weak acid to lose a proton at a given pH
what is the formula for pka and ka
pka is the negative log of ka
ka is base x h30+ / acid
What happens to an acid base equilibrium when strong acid is added?
protons combined with conjugate base to produce more weak acid
What happens to an acid base equilibrium if strong base is added?
strong base (OH-) takes proton from the weak acid to produce weak base and water
What are the three blood buffers that maintain blood pH?
bicarbonate buffer
phosphate buffer
protein buffer
Describe the pathway of carbon dioxide and bicarbonate in the blood during exercise
- Carbon dioxide leaves the body tissue and travels into the blood capillary where CO2 reacts with H2O (and carbonic anhydride enzyme) to from carbonic acid. (lowers blood pH)
- Carbonic acid then dissociates to bicarbonate and hydrogen
How is blood pH maintained during exercise i.e. explain the interplay between buffer, respiratory and renal systems
- during exercise, cell metabolism increases, more CO2 produced
- More CO2 dissolves in blood forming carbonic acid (lowering blood pH)
- Receptors in the brain sense this change and send nerve impulses to increase breathing rate
- Increased breathing rate removes CO2 from the blood and blood pH returns back to normal
Explain how fast the buffer systems in the body work to regulate blood pH
the blood buffering equilibrium responds the quickest.
Order is chemical buffering (seconds), breathing (minutes), and renal system (hours and days).
Define a prion
- infectious proteins and virtually indestructible, no genetic material in it
- mis-shapen version of normal brain proteins they interact with normal version and covert them to the diseased state in a chain reaction
What is the normal structure of a Prp-sen
alpha helix
What is the structure of a PrP-res (disease causing)
beta sheets
Describe how the diseased prions fold and become so strong
beta sheets aggregate and form long fibril structures that form fibres “amyloid fibrils”
- very low energy state thus driving the formation of disease - no coming back from these
- very stable due to extensive hydrogen bonding (INTERMOLECULAR)
How we can design inhibitors to bind more
strongly than a substrate molecule?
- look like substrate (right size and shape and forming strong interactions)
- best inhibitors/drugs are
designed as transition state analogues (looking like or mimicking the TS - lower the activation energy of
a reaction, specifically lowering the TS energy. - Inhibitors or drugs might bind into pockets the substrate does not - new
interactions (inhibitor or drug binds with 10,000 times more affinity than the substrate and outcompetes the substrate for binding.
