01 Chemistry of Life

Question 1

List the four requirements of life on Earth and how these ideas were backed up experimentally.

Answer 1

1. Simple gaseous molecules eg. NH3, CH4, H2
2. Liquid water - from condensation as the earth cooled, new molecules formed in water
3. A reducing environment - low oxygen environment is supportive of bond formation of C, N, O and H
4. 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

Question 2

What is the bond between amino acids called? What do they form?

Answer 2

peptide bond or amide bond. Polypeptide or proteins

Question 3

What is the bond between nucleotides called? What do they form?

Answer 3

phosphodiester bond. Polynucleotides or nucleic acids (DNA or RNA)

Question 4

What is the bond between saccharides called? What do they form?

Answer 4

glycosidic linkages. polysaccharide/carbohydrates

Question 5

Name the 7 different types of interactions

Answer 5

charge-charge, charge-dipole, charge-inducted dipole, dipole-dipole, dipole induced dipole, Dispersion (van der waals) and Hydrogen bonds

Question 6

Why do molecules use weak interactions internally (intramolecular)? Give an example

Answer 6

• 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)

Question 7

Why do molecules use weak interaction to interact with other molecules (intermolecular)? Give an example

Answer 7

• 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

Question 8

How much distance are DNA base pairs from each other when stacked?

Answer 8

0.34 nm or 3.4 Å

Question 9

What is the closest distance atoms can approach each other without repulsing each other?

Answer 9

The closest approach attracting atoms can make is the sum of their vdW radii.

Question 10

How do hydrogen bonds differ from vdW interactions in terms of radii? What does this tell us about the nature of a H-bond?

Answer 10

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.

Question 11

How does water interact with Ionic Compounds?

Answer 11

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.

Question 12

How does water interact with Polar Molecules?

Answer 12

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

Question 13

How does water interact with Hydrophobic molecules?

Answer 13

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

Question 14

How do amphipathic molecules behave in aqueous solution?

Answer 14

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)

Question 15

Why is the lipid bilayer essential for life on earth?

Answer 15

1. it is relatively impermeable - barrier controlling which molecules can cross form one side to the other
2. 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)

Question 16

What properties of water make it such an important molecule in biology?

Answer 16

1. small, polar and hydrogen (4) bonding potential
2. liquid most of the time on Earth because of the size and extensive hydrogen bonding
3. dissolves ionic and polar molecules
4. drives amphipathic molecules like lipids to assemble into higher order structures like bilayers and vesicles. this is the hydrophobic effect in action
5. 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.

Question 17

at pH < pKa side chain is found in the …

Answer 17

acid from, protonated

Question 18

at pH = pKa side chain is found in the

Answer 18

equal amounts, 50:50 mixture, de-protonated and protonated

Question 19

at pH > pKa base side chain is found in the …

Answer 19

base form, de-protonated

Question 20

Multiple protein conformational states of an unfolded protein FAVOUR/DISFAVOUR folding? Explain.

Answer 20

Disfavour (entropy is high, favourable)

Question 21

The formation of new weak interaction FAVOURS/DISFAVOURS folding? Explain.

Answer 21

Favours, hydrogen bonds, vdW are stable and favoured

Question 22

The hydrophobic effect FAVOURS/DISFAVOURS folding? Explain.

Answer 22

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.

Question 23

Define the term “metamorphic” in terms of protein folding

Answer 23

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)

Question 24

Explain why the hydrophobic effect is so critical for protein folding

Answer 24

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

Question 25

Does protein folding require energy? Explain

Answer 25

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.

Question 26

Where does the energy for protein folding come from?

Answer 26

1. formation of new weak interactions in protein folding releases energy - new hydrogen bonds and vdW interactions are favourable - lowers the energy of the system
2. the hydrophobic effect - non polar hydrophobic molecules (side chains) in solution will come together

Question 27

What is amyloid disease?

Answer 27

the build up of abnormal protein called amyloid

Question 28

Describe how amyloid disease occurs in terms of protein folding and aggregation?

Answer 28

1. a healthy protein unfolds and then forms a misfolded version of the protein now containing beta sheet structures.
2. 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
3. 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.

Question 29

What bond types dominate in diseased proteins? Explain the significance.

Answer 29

In the disease forms, intermolecular weak interactions start to dominate and make these structures stable.

(in normal proteins intramolecular interactions dominate)

Question 30

What is molecular recognition?

Answer 30

refers to the specific interaction between two or more molecules through weak interactions and includes shape, size (length, radius, diameter) and feeling/WEAK INTERACTIONS.

Question 31

What is an oxyanion hole? What is its significance?

Answer 31

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.

Question 32

Which area of proteins forms interactions with other proteins?

Answer 32

Side chains NOT the amino or carboxyl terminals!!!

Question 33

What are the three rules of folding that apply to proteins?

Answer 33

1. Number of conformations/states unfolded vs. folded
2. Formation of new weak interactions
3. Hydrophobic effect

Question 34

Describe how DNA follows the three rules of protein folding

Answer 34

1. 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).
2. Formation of new weak interactions-
   DNA base-pairing (hydrogen bonding) and the DNA base stacking (vdW)
   interactions found in the folded DNA.
3. 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.

Question 35

Define ionisable groups

Answer 35

Functional groups that act as proton-donor or proton acceptor influence the capacity for a molecule to act as an acid or base.

Question 36

Define pka

Answer 36

describes the propensity of a weak acid to lose a proton at a given pH

Question 37

what is the formula for pka and ka

Answer 37

pka is the negative log of ka

ka is base x h30+ / acid

Question 38

What happens to an acid base equilibrium when strong acid is added?

Answer 38

protons combined with conjugate base to produce more weak acid

Question 39

What happens to an acid base equilibrium if strong base is added?

Answer 39

strong base (OH-) takes proton from the weak acid to produce weak base and water

Question 40

What are the three blood buffers that maintain blood pH?

Answer 40

bicarbonate buffer
phosphate buffer
protein buffer

Question 41

Describe the pathway of carbon dioxide and bicarbonate in the blood during exercise

Answer 41

• 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

Question 42

How is blood pH maintained during exercise i.e. explain the interplay between buffer, respiratory and renal systems

Answer 42

• 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

Question 43

Explain how fast the buffer systems in the body work to regulate blood pH

Answer 43

the blood buffering equilibrium responds the quickest.

Order is chemical buffering (seconds), breathing (minutes), and renal system (hours and days).

Question 44

Define a prion

Answer 44

• 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

Question 45

What is the normal structure of a Prp-sen

Answer 45

alpha helix

Question 46

What is the structure of a PrP-res (disease causing)

Answer 46

beta sheets

Question 47

Describe how the diseased prions fold and become so strong

Answer 47

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)

Question 48

How we can design inhibitors to bind more

strongly than a substrate molecule?

Answer 48

• 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.