Building Blocks I: Amino Acids Flashcards
What conditions are to be met for a natural amino acid?
- 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
What is the term isoelectric point mean?
- When molecules are ionised to the point where there are no net charges. (zwitterion)
- Amino acids become least soluble
What are proteinogenic amino acids?
- Precursors to protein
- Have 4 main subgroups
- Non-polar aliphatic
- Aromatic
- Uncharged polar
- Charge polar
Non-polar aliphatic amino acids interactions?
- London dispersion forces
- Steming from random dipole moments
- Stabilises folded protein conformation
Amino acids with charged R groups interactions?
- Charged at physiological pH
- Contributing to electrostatic interactions
- Highly soluble in aqueous environment
What is an amide bond and what does it do?
- 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
What are the different intermolecular forces in an amino acid?
- 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
What are the different levels of organisation for protein structures?
- Primary
- Secondary
- Alpha helices
- Beta sheets - Tertiary
- Fibrous proteins
- Globular proteins - Quaternary
Describe the primary structure of a protein
- Covalent peptide linkages
Describe the secondary structure of a protein
- 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
Describe the tertiary structure of a protein
- 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
Describe the quaternary structure of a protein
- Multiple protein subunits to support a specific function
- Polar and non-polar interactions (Hydrophillic and hydrophobic)
- Misfolding causes diseases
What are the different functions of amino acids?
- Conjugation
- Phosphorylation
- Carboxylation
- Glycosylation (sugar attachment)
- Lipid attachment - Oxidation
- Proline oxidation
- Disulfide bond attachment - Hydrolysis
What is phosphorylation?
- Hydroxyl group containing amino acids
- “anchors” formation triggering protein binding
- Phosphorylation prevention used as drug therapy
What is carboxylation?
- With glutamate
- Mediated by vitamin K to form gamma-carboxy glutamic acid.
What is glycosylation?
- Addition of sugar to protein structures
- Surface properties are altered.
- N-linked and O-linked glycosylation
What is lipid attachment?
- Tethers soluble proteins to membranes for sub cellular localisation for biological function
- Attached covalently via
- N-terminus
- C-terminus
- Thioester linkage with Cysteine
What is proline hydroxylation?
- Adds addition hydrogen bonds for folding and assembly of mature proteins
- Triggered by enzymes called hydroxylases
What is disulfide linkages?
E.g. Cysteine oxidation
- Inter and intramolecular
- Maintains protein structure and oxidation state
What activities does hydrolysis of proteins do?
- Regulate protein function (E.g. Pro-insulin to insulin)
- Degradation (e.g. Actions of caspases) Cysteine dependent, Aspartame directed proteases
- Sequencing and identification
What are essential and non-essential amino acids?
- Essential AA: Supplied through diet
- Non-Essential: Synthesized from other AA or precursors
What are the different applications of cysteine?
- Folding and maturation of 3rd structure
- Reducing agent for cellular oxidisation
- Stops reactions of reactive species
- Thiol group helps to stop the rxn
- Derivatives are normally used
What does N-acetylcysteine do? Part 1
- Acts as a mucolytic agent
- Breaks down disulfide linkages between mucus proteins, reduces cross-linking bewtween peptides, making it less sticky and viscous
What does N-acetylcysteine do? Part 2
- Paracetamol poisoning treatment
- Binds to electrophillic site of toxic intermediate
- Less reactive to other proteins
- Easily soluble in proteins and easily excreted
