Building Blocks I: Amino Acids

Question 1

What conditions are to be met for a natural amino acid?

Answer 1

• Carboxylic group
• Hydrogen
• Amino group
• R group
  All on a chiral carbon in L-conformation
• Amphoteric (Able to interact with both acids and bases)
• R group ionisable, can affect physiochemical properties of AA

Question 2

What is the term isoelectric point mean?

Answer 2

• When molecules are ionised to the point where there are no net charges. (zwitterion)
• Amino acids become least soluble

Question 3

What are proteinogenic amino acids?

Answer 3

• Precursors to protein
• Have 4 main subgroups
  • Non-polar aliphatic
  • Aromatic
  • Uncharged polar
  • Charge polar

Question 4

Non-polar aliphatic amino acids interactions?

Answer 4

• London dispersion forces
• Steming from random dipole moments
• Stabilises folded protein conformation

Question 5

Amino acids with charged R groups interactions?

Answer 5

• Charged at physiological pH
• Contributing to electrostatic interactions
• Highly soluble in aqueous environment

Question 6

What is an amide bond and what does it do?

Answer 6

• Amide bond = peptide bond (Covalent)
• Between COOH and NH2
• Partial double bond due to delocalisation.
• No rotation on axis
• Not much ionisation with pH changes
• Charges usually arise from R groups or termini (N-terminus or C-terminus)
• N-terminus refers to a start of the amino chain with a NH2 group
• C-terminus refers to the end of a amino chain with a COOH group

Question 7

What are the different intermolecular forces in an amino acid?

Answer 7

• Hydrogen bonds
  
  • Bet peptide bonds, R groups
• Van der Waals interactions
  
  • aliphatic side chains
• Hydrophobic interacaction
  
  • Bet aliphatic and phenyl side chains
• Electrostatic interactions
  
  • Between charged side chains
• Covalent bonds
  
  • Disulfide bonds between cysteines

Question 8

What are the different levels of organisation for protein structures?

Answer 8

1. Primary
2. Secondary
   - Alpha helices
   - Beta sheets
3. Tertiary
   - Fibrous proteins
   - Globular proteins
4. Quaternary

Question 9

Describe the primary structure of a protein

Answer 9

• Covalent peptide linkages

Question 10

Describe the secondary structure of a protein

Answer 10

• Hydrogen bonding between amino and carbonyl groups
• Alpha helices
  
  • H-bonding between amino group (n) and carbonyl group (n+4)
  • Proline (non essential aa) usually ends the helix
• Beta sheets
  
  • H-bonding between adjacent peptide groups
  • Parallel (N terminus together, C terminus together)
  • Anti-parallel (C+N terminus together)
  • Single chain folded together

Question 11

Describe the tertiary structure of a protein

Answer 11

• H-bonding of side chains, Van der Waals, disulfide linkages (covalent), hydrophobic interactions
• Fibrous proteins
  
  • Usually chains of alpha helices (collagen) or stacking of beta sheets (b-keratin)
  • Helices folding into globular structure
  • myoglobin or haemoglobin
  • Usually have the polar side chains facing outwards, non-polar areas facing inwards.
  • Increased solubility

Question 12

Describe the quaternary structure of a protein

Answer 12

• Multiple protein subunits to support a specific function
• Polar and non-polar interactions (Hydrophillic and hydrophobic)
• Misfolding causes diseases

Question 13

What are the different functions of amino acids?

Answer 13

1. Conjugation
   - Phosphorylation
   - Carboxylation
   - Glycosylation (sugar attachment)
   - Lipid attachment
2. Oxidation
   - Proline oxidation
   - Disulfide bond attachment
3. Hydrolysis

Question 14

What is phosphorylation?

Answer 14

• Hydroxyl group containing amino acids
• “anchors” formation triggering protein binding
• Phosphorylation prevention used as drug therapy

Question 15

What is carboxylation?

Answer 15

• With glutamate

- Mediated by vitamin K to form gamma-carboxy glutamic acid.

Question 16

What is glycosylation?

Answer 16

• Addition of sugar to protein structures
• Surface properties are altered.
• N-linked and O-linked glycosylation

Question 17

What is lipid attachment?

Answer 17

• Tethers soluble proteins to membranes for sub cellular localisation for biological function
• Attached covalently via
  
  • N-terminus
  • C-terminus
  • Thioester linkage with Cysteine

Question 18

What is proline hydroxylation?

Answer 18

• Adds addition hydrogen bonds for folding and assembly of mature proteins
• Triggered by enzymes called hydroxylases

Question 19

What is disulfide linkages?

E.g. Cysteine oxidation

Answer 19

• Inter and intramolecular

- Maintains protein structure and oxidation state

Question 20

What activities does hydrolysis of proteins do?

Answer 20

• Regulate protein function (E.g. Pro-insulin to insulin)
• Degradation (e.g. Actions of caspases) Cysteine dependent, Aspartame directed proteases
• Sequencing and identification

Question 21

What are essential and non-essential amino acids?

Answer 21

• Essential AA: Supplied through diet

- Non-Essential: Synthesized from other AA or precursors

Question 22

What are the different applications of cysteine?

Answer 22

1. Folding and maturation of 3rd structure
2. Reducing agent for cellular oxidisation
3. Stops reactions of reactive species
   - Thiol group helps to stop the rxn
   - Derivatives are normally used

Question 23

What does N-acetylcysteine do? Part 1

Answer 23

• Acts as a mucolytic agent
  
  • Breaks down disulfide linkages between mucus proteins, reduces cross-linking bewtween peptides, making it less sticky and viscous

Question 24

What does N-acetylcysteine do? Part 2

Answer 24

• Paracetamol poisoning treatment
• Binds to electrophillic site of toxic intermediate
• Less reactive to other proteins
• Easily soluble in proteins and easily excreted