Proteins

What are amino acids?

Monomers, building blocks for proteins

What is physiological pH?

A pH level that matches the normal, healthy environment inside the human body

What is a zwitterion?

A neutral molecule that contains an equal amount of positive and negative charges on different functional groups, resulting in a net charge of zero

At physiological pH, which part of an amino acid is most directly responsible for distinguishing one standard amino acid from another?

The R group

Why are the R groups still important if they aren’t the groups that form the peptide bond?

They determine many of the proteins chemical properties and help influence its folding for example,

• Hydrophobic R groups tend to cluster inside soluble proteins, away from water

• Polar R groups can form hydrogen bonds with water and other molecules

• Charged R groups can form ionic interactions with oppositely charged groups

Link the property of an R group to clinical practice

• The change of an R group contributes to sickle cell disease because normal haemoglobin contains the amino acid glutamate at position 6 of its Beta globin chain

• In sickle cell disease, this glutamate is replaced by valine

• Glutamate has a negatively charged side chain, whereas valine has a hydrophobic, non - polar side chain

• This encourages deoxygenated haemoglobin molecules to stick together forming fibres that can distort red blood cells into a sickle shape

Why do hydrophobic R groups tend to be found in the interior of many soluble proteins?

They tend to avoid contact with water, so folding can bury them inside a protein

• important to note that this is a general pattern and not a rule as some of these hydrophobic R groups can be exposed, some are polar or charged residues are found inside proteins where they can form stabilising interactions

What is the name of the covalent bond that joins two amino acids together during protein synthesis?

Peptide bond

What are the distinctions of the bonds in terms of amino acids?

• Peptide bond covalently links amino acids in the protein backbone

• Hydrogen bond helps stabilise protein structure, including alpha helices and beta pleated sheets

• Ionic interaction is the attraction between oppositely charged groups, including some amino acid side chains

• Disulfide bonds form between the sulfur atoms of two cysteine side chains, helping to stabilise the protein’s three dimensional structure

What do the different lines mean on the amino acid?

• straight line is the bond in the plane, so drawn as lying in the plane of the page or screen - it represents the covalent bond between two atoms

• solid wedge is the bond coming towards you as broad end represents a bond projecting out of the page towards the viewer

• dashed wedge is the bond going away from you as the bond projects behind the plane of the page away from the viewer

What does superimposed mean and how does it link to chirality?

To superimpose something is to place an object, image, text or layer on top of another so that both elements remain visible at the same time

Chiral is an object strucutre or molecule that cannot be superimposed on its mirror image

What does it mean by proteinogenic amino acids

They are amino acids that are genetically coded and used by ribosomes to make proteins during translation (not all of them though, but the majority)

What are the four protein structures?

• Primary which is the sequence of amino acids

• Secondary which is the local spatial arrangement of polypeptide backbone

• Tertiary which is the 3D structure of the whole polypeptide including the side chains

• Quaternary which is the assembly of several polypeptide chains

What is a residue?

An amino acid unit within a protein chain after it has lost its orginal structure during bond formation

What is the Valence, Shell Electron Pair Repulsion theory?

Electron regions arrange themselves to minimise repulsion by staying as far apart as possible

What are enantiomers?

Enantiomers are pairs of molecules that are non - superimposable mirror images of eachother

What are the two forms of amino acids?

L and D forms

L form of amino acid is overwhelmingly abundant in nature

D forms can also exist in bacterial cell walls and certain peptides

• They have the same atoms and bonds yet they differ in their spatial arrangement

• They are non - superimposable so you cannot line them up directly no matter how much you turn, rotate or flip them in space

• Chiral

When is carbon classed as being a chiral centre?

All the groups attached to it must be different

What is stereospecificity?

Enzymes can distinguish between different stereoisomers because of their specific three - dimensional structures

Which amino acids are deeemed hydrophobic, nonpolar and non - aromatic? Provide any additional information if necessary

Alanine, Valine, Leucine, Isoleucine, Methionine, Glycine and Proline

• Glycine is a special one because it contains a hydrogen atom on its side chain (it is the simplest amino acid), so it provides flexibility to protein structures - despite being in the hydrophobic category, it is often deemed to be ambivalent or neutral because its tiny size allows it to fit easily into both hydrophobic and hydrophilic environments

• Proline is also unique because of its cyclic structure that incorporates the amino nitrogen and restricts flexibility

• Methionine contains a sulfur atom within a thioether group which is often involved in initiating protein synthesis

What is aromatic?

An organic compound that contains one or more benzene or equivalent heterocyclic rings

What is the difference between polar and non - polar?

• Polar: the atoms share the electrons unevenl/ unequally as one atom has a higher electronegativity and this creates a dipole so one side has a partial negative charge and the other side has a partial positive charge

• Non - polar: the atoms share electrons qually because they have a similar or identical pulling power

What are examples of aromatic amino acids? provide more information if necessary

• Phenylalanine is non polar, contains a benzyl ring which contributes to the hydrophobic core

• Tyrosine is polar because of the hydroxyl group attached to it and it has a structure that is vital to signalling pathways using tyrosine kinase receptors

• Tryptophan is the largest amino acid with a complex double ring that includes a nitrogen atom and plays an essential role in protein - protein interactions

What are examples of polar, uncharged amino acids? provide any additional information if necessary

Serine and threonine both contain hydroxyl groups which are often involved in phosphorylation (hydrophilic)

Cysteine has a thiol group, this makes it reactive, prone to forming disulfide bonds and this is crucial for protein stability

Asparagine and glutamine contain amide groups that do not gain or lose protons, remaining neutral in charge and often involved in hydrogen bonding

Which amino acids are deemed to be charged?

Aspartic acid and glutamic acid both contain carbonyl groups in their side chains which lose protons and become negatively charged and are often involved in active sites of enzymes

Lysine contains a terminal primary amino group (the end of a molecule features a free, unbonded NH2 where the nitrogen is attached to one carbon and two hydrogen atoms)

Arginine contains a guandinium group (planar y shaped, positively charged functional group found in organic molecules) making it highly basic and often involved in protein binding. It is highly basic and often involved in protein binding

Histidine contains an imidazole ring (a planar, five - membered heterocyclic aromatic compound with the chemical formula C3H4H2), which can shuffle protons, playing a crucial role in enzyme active sites and buffering

What are the nine standard amino acids that the body cannot synthesise on its own, thus has to get through dieting?

• Hisitidine

• Isoleucine

• Leucine

• Lysine

• Methionine

• Phenylalanine

• Threonine

• Tryptophan

• Valine

What are conditionally essential amino acids?

These amino acids can normally be synthesised in the body, but certain conditions such as rapid growth in children, severe illness, injury or metabollic stress means that the body cannot make enough of them

• Arginine

• Cysteine

• Glutamine

• Glycine

• Proline

• Tyrosine

What are the different post translational modifications that proteins can undergo?

Phosphorylation which is the addition of phosphate groups, usually serine, threonine or tyrosine (play critical role in signalling pathways)

Glycosylation which is the attachment of carbohydrate groups, affecting protein stability, folding and cell recognition

Acetylation and Methylation which are modifications that typically occur on lysine residues, influencing gene expression and protein function.

Ubiquitination which is the attachment of ubiquitin to lysine residues, tagging proteins for degradation.

What is the order of protein strucutre?

Primary structure is the sequence of amino acids within the polypeptide chain

What can result when there is a change in the gene’s DNA sequence?

A change in the amino acid sequence of the protein