Lecture 3: Amino Acid Structures and Properties

Side info: Case Study

• Strength training, influencers promote branched-chain amino acids supplements

• BCAA are also found in foods with high in proteins

• Are these scientifically accurate claims

How can be distinguish between different amino acids?

• which two interactions required for holding the protein together and interacting with other molecules

• why is hydrophilic AA important?

• distinct side chains that contributes to the protein’s structure and function

• Non-covalent and covalent interactions between function groups essential to hold the protein together and interact with other molecules

• interactions of water and hydrophilic AA help solubize proteins

What are proteins made up of?

• what is the chain called

• what are three components of a singular AA

• why are they important for diet

• proteins made up of polymers of AA residues linked together through peptide and amide bonds to form polypeptides

• AA made up of the amino group, carboxyl group and the side chain R

• some AA essential in diet (as we cannot make it ourselves) and

  • Non-essential can be made from metabolites that we already have in the body (synthesized)

  • *don’t need to memorize which are essential and which are non-essential

state the six letters that don’t associate with one letter amino acids

JUZBOX

Chiral Amino Acids

• when is the AA consider chiral?

• Two characteristics of chiral molecules - what is this molecule called

• What else (type of molecules) also exhibit optical activity

• Why are L amino acid important - why do they only use this, instead of their mirror image D isomer?

• the asymmetric alpha carbon (all groups attached but be different from each other) results in chirality

• Characteristics - for enantiomers

  • non-superimposable

  • Mirror images

• isomers also exhibit optical activity

• L amino acids are physiologically relevant structures found in plants and animal proteins

• Q to mentimeter: Ila, leu val

• Glycine is not chiral (the only one)

Why do human cells only use L-amino acids

• protein syntheses have evolved to recognize and incorporate L-amino acids, D are left to the side and not use

  • D can be used in inhibitors, still bind a form some reactions but runs cannot occur

• D-amino acid can still participate in non-covalent interactions, but doesn’t occur in human cells

• Both can form peptide bonds and are both similarly chemically stable

The 20 standard amino acids at pH 7.4

Non-covalent Interactions

• With groups can form an H bond with water? (4 groups)

• H bonding within the backbone or side chains

• Hydrophobc interactions between what two things in a protein

• Ionic interactions (why are they important, 3 things)

• Salt bridges

• H bonds can form between hydroxyl, carboxyl, thiol and amino groups to help with protein solubility

• H bonds can form between AA side chains or backbone within a protein’s structure

• Hydrophobic interactions can occur between aliphatic and hydrophobic side chains (with only H and C atoms in their side chain)

• Ionic interactions are important for ligand, cofactor and/or substrate binding in enzymes (charged molecule in the picture of the amino acids)

  • Salt bridges can form between positively and negatively charged amino acids as well

Disulfide bonds

• When does the bond occur

• What two locations can it occurs

• Why are the bonds important

• What enzymes help in the bonding process (in which specific part of the rnx)

• What does the bonding produce?

• covalently cross-link two cysteines together

• Bonds can occur in an intrachain or between two polypeptide chains

• Linkages stabilize structures - very strong disulfide bond

• Protein Disulfide Isomerase PDI enzymes can help catalyze the oxidization rxn

• Bonding process produces 2H+ and 2 e-

Secreted vs Cytosolic proteins

• When are disulfide bonds formed (in which part of the cell) in secreted cells

• How are disfulfide bonds formed for cytosolic proteins

• How are the disulfide bonds broken

• Secreted proteins: Post-translational modification occur in secreted proteins once passed through the ER

• Cytosolic proteins contain free cysteines due to the reducing nature of the cytosol (they do not form disulfide bonds (reduction occurs which breaks the disulfide bonds)

• for both, the bonds can be broken by the reducing agents in the cytosol or in the lab

Hydrophobic amino acids

• where are most regions found

  • (two locations and why)

• Within the proteins: the maximize the hydrophobic interactions (away from water)

• A little bit on the surface: to allow for non-covalent interactions

Post-translational modifications

• what can be modified of the side chains (two things and two affects)

  • Remind yourself about the disulfide bond

• Four important covalent modifications

• Removal or addition of functional groups, changes the structure and thus changes it’s function or begin the proteins degradation

• The disulfide bond is an example of a post-translational modification

• Important covalent modifications

  • Phsophorylation

  • Ubiquitination (degradation)

  • Glycosylation

  • Acetyl, methyl, hydroxyl, and carboxyl (adding functional groups)

• Cofactor/ligand binding is also important

Amino acid modifications

• hydroxyproline

• carboxyglutamate

• Carbohydrate-asparagine adduct

• Phosphoserine

• hydroxyproline

• carboxyglutamate

• Carbohydrate-asparagine adduct

• Phosphoserine

Histone Acetylation (PTM)

• In what location does this occur

• occurs on key lysine residues affecting gene regulation

• The molecule, lysine become more neutral, not binding to DNA as strongly

Amino acid metabolism

• what can it be metabolized to form (4 possible molecules)

• hormones

• neurotransmitters

• nitrogenous bases (DNA/RNA)

• energy-producing intermediates (proteins sometimes used for energy)

Amino Acid Derivative

Amino Acid Properties

• what does the sequence determine about the protein

  • Why is the primary sequence important (what info does it provide us with)

• What does mutation lead to?

• amino acid sequence determines the 3D structure of proteins, revealing their evolutionary history

  • Also making it easier to determine the protein’s functions with homology searches (similar functions of the ancestor)

• Mutations in primary sequence changes the function and/or lead to disease

Types of mutations

• silent: changes the codon but not the protein being made

  • E.g. UUU to UUC

• non-conservative: changes the proteins properties

  • E.g UUU to UCU (changed hydrophobic to polar)

• Conservative: conserves the properties - or doesn’t

  • E.g. UCU to