B.2 - SL Proteins and Enzymes

AMINO ACIDS AND PROTEINS

Proteins are polymers of 2-amino acids, joined by amide links (also known as peptide bonds).

WHAT ARE PROTEINS?

Proteins make up all human tissues like muscles, skin, hair, fingernails and more less obvious things like enzymes. Proteins are made from amino acids which react in a condensation reaction and bond together through peptide bonds to form protein chains.

WHAT’S THE CHEMISTRY?

All amino acids have a common structure, they have a carboxylic acid group, and an amine group. The ‘R’ group which you’re hopefully familiar with from organic chemistry, determines which amino acid it is. There are 20 different naturally occurring amino acids, the simplest of which is glycine where the R group is just H. This R group be anything though.

Amino acid structure (functional groups)

This diagram will be discussed more below (zwitterions), don’t worry if it’s confusing

Glycine
Phenylalanine

This R group vastly affects the properties of the amino acid.

ZWITTER IONS

Amino acids are amphoteric and can exist as zwitterions, cations and anions.
 Application of the relationships between charge, pH and isoelectric point for amino acids and proteins.

Amino acids are amphoteric because of the general structure discussed above. All amino acids have a carboxylic acid group (acidic) and an amine group (basic). This makes amino acids amphoteric because they can react with both acids and bases.

LOW PH

In a low pH situation, the amine group reacts with H+ to form a cation.

Low pH effect on amino acids

HIGH PH

At a high pH, the carboxylic acid group reacts with OH- to form an anion.

High pH effect amino acids

ZWITTER IONS

Zwitterions (Zwitter ions) are when a molecule is both an anion and a cation at the same time. This can occur with amino acids. At a certain pH, amino acids have both a H3N+ group, and a COO- group.

Amino acid zwitterion diagram

EFFECT OF THE R GROUP ON AMINO ACID PROPERTIES

Explanation of the solubilities and melting points of amino acids in terms of zwitterions.

pI - ISOELECTRIC POINT

The pH at which this zwitterion occurs is called the Isoelectric point (pI). Every amino acid has it’s own isoelectric point, which is dependant on the R group. An acidic R group leads to a lower pI and a basic R group leads to a higher pI.

Aspartic acid pI

An extra COOH group in the R group leads to a low pI

Glycine pI

Only a H for the R group leads to a pI of 6

Arginine pI

Several NH and NH2 groups in the R group leads to a high pI

At a pH higher than that of the isoelectric point, a cation will form and at a pH lower than the isoelectric point, an anion will form.

MELTING POINT

As you will have learnt in topic 4, melting points are dependant on Intermolecular Forces (IMFs). An R group with a large amount of intermolecular forces will cause the amino acid to have a high melting point. This syllabus statement is basically a repeat of what has already been learnt in topic 4.

SOLUBILITY

Same as above. A more polar R group will be more soluble, just like you learnt in topic 4.

PROTEIN STRUCTURES

Protein structures are diverse and are described at the primary, secondary, tertiary and quaternary levels.
Description of the four levels of protein structure, including the origin and types of bonds and interactions involved.

PRIMARY STRUCTURE

This is a protein’s one dimensional structure. This is just looking at the sequence of amino acids that are joined to each other.

SECONDARY STRUCTURE

This is looking at proteins on a broader level. Protein chains can fold or coil depending on intramolecular forces in the protein chain. There are two types of secondary structures that proteins can form (besides straight chain).

ALPHA HELIX

Alpha helix (secondary structure)

Basically a cool looking spiral shape. This is caused by intermolecular forces between different sections of 1 chain that forces the protein into a helix shape. It’s usually drawn as a ribbon so that it’s helix structure is more easily seen.

BETA PLEATED SHEET

Beta pleated sheet (secondary structure)

The beta pleated sheet occurs when 2 or more chains (or parts of chains) ‘line up’ due to intermolecular forces and form a sheet

Beta pleated sheet (secondary structure)

TERTIARY STRUCTURE

This is an even broader look at a protein. In 1 protein, there’s likely to be sections that have an alpha helix structure, and some sections with a beta sheet structure. Looking at the protein chain as a whole is looking at it’s tertiary structure.

Tertiary structure (proteins)

This diagram shows the tertiary structure of this protein, which has a mixture of alpha helices and beta sheets.

QUATERNARY STRUCTURE

Quaternary structure (proteins)

An again broader view of proteins. The tertiary structure looked at only one protein chain. The quaternary structure could have multiple chains bonded together. A common example of this is haemoglobin, which has 4 protein chains bonded together.

EFFECT OF SHAPE ON FUNCTION

A protein’s three-dimensional shape determines its role in structural components or in metabolic processes.

GLOBULAR PROTEINS

Haemoglobin is an example of a globular protein. Globular proteins usually have complex tertiary and quaternary structures, and are usually somewhat spherical. Because of their complex structure, they are more heat sensitive. The protein chain in a globular protein usually has it’s polar R groups exposed, and is therefore more soluble in water.

FIBROUS PROTEINS

Fibrous proteins have little or no tertiary or quaternary structures at all, and form long fibres. This structure makes them much ‘stronger’ than globular proteins. Their polar R groups are not exposed like in globular proteins, making them insoluble. Examples of fibrous proteins would be  in hair, skin and bones, where insolubility and structure are needed.

ENZYME BASICS

Most enzymes are proteins that act as catalysts by binding specifically to a substrate at the active site.

Enzyme structure

An example of an enzyme

Enzymes are biological catalysts that speed up reactions within the body. Enzymes are usually complex proteins.
Some examples of enzymes are:

Enzymes have an active site where the substrate binds to and where the reaction occurs.
Basic enzyme mechanism

A simple diagram of the mechanism of an enzyme catalysed reaction. More on this later…

ENZYME MODELS

LOCK AND KEY

The lock and key model is the most basic model of enzymes, that is shown above.

INDUCED FIT MODEL

The induced fit model suggests that the enzyme plays a role in forming the shape of the active site. The intermolecular forces from the substrate therefore help mould the shape of the active site so that the substrate fits.

Induced fit enzyme model

ENZYME ACTIVITY

As enzyme activity depends on the conformation, it is sensitive to changes in temperature and pH and the presence of heavy metal ions.

EFFECTS OF PH AND TEMPERATURE ON ENZYMES

pH and temperature both have the effect of denaturing the enzyme. Denaturing just means that the active site has been damaged and can no longer function.

Enzymes all have their own ranges of temperature and pH that they work at. For most enzymes, this is the temperature and pH of most organisms.

Each enzyme has a different optimum pH and temperature depending on where they operate in the body. Some examples are:

  • Amylase (in the mouth)
    • pH 6.7
    • 32-37 C
  • Catalase (in plants)
    • pH 7
    • 48C
  • Protease (in the stomach)
    • pH 1.6
    • 50C

HEAVY METAL IONS

Heavy metal ions act as non-competitive inhibitors. This is a HL concept from B.7 so I won’t include the details in this post but the long and the short of it is that it indirectly destroys the active site.

ENZYME ACTIVITY

Deduction and interpretation of graphs of enzyme activity involving changes in substrate concentration, pH and temperature.

This is basically the kinetics of enzymes. The graphs you will come across here are graphs of Rate of Reaction against Substrate concentration. Because an enzyme can only work at a certain maximum rate, the graph curves off and a maximum rate of reaction is seen.

Enzyme assay graph

From this maximum, a ‘half max’ can also be calculated a bit like they do for half life in physics (and medicinal chem <3). This ‘half max’ is used to calculate a constant called the Michaelis constant (Km). Every enzyme has a different Michaelis constant.

A small Km value suggests that an enzyme only needs a small concentration on substrate to become saturated, and a large Km value suggests that an enzyme needs a large concentration of substrate to become saturated.
 
Long story short: The smaller the Michaelis constant, the ‘worse’ an enzyme is at catalysing reactions in that you need a lot more of it to reach the same rate of reaction compared to an enzyme with a larger Michaelis constant.

EFFECT OF PH AND TEMPERATURE (GRAPHS)

The graph of Rate of Reaction against pH looks like a bell curve, with the largest value for the Rate of Reaction indicating the optimum pH
pH effect on enzymes

Enzyme activity plotted against pH for 2 different enzymes

The graph of Rate of Reaction against temperature looks different. This is because at low temperatures it does not denature unlike when the pH is low.
Temp. effect on enzymes

CHROMATOGRAPHY AND ELECTROPHORESIS

Chromatography separation is based on different physical and chemical principles. 
Explanation of the processes of paper chromatography and gel electrophoresis in amino acid and protein separation and identification.

CHROMATOGRAPHY

Hopefully you remember this from GCSE. Chromatography is the separation of different substances based on their solubility in a solvent.

Chromatography diagram

Chromatography also doesn’t necessarily need to be done using paper, it can also be done using a gel 🙂

ENZYME CHROMATOGRAPHY

An unknown mixture of enzymes can be analysed using chromatography and matching up the different ‘spots’ from that mixture with samples of known enzymes.
 
The enzymes will travel at different speeds with the solvent depending on how soluble their R group is in water. Sometimes however, some enzymes will travel exactly the same distance in a solvent. In this case, chromatography is done twice along the 2 planes of the paper.
  1. A spot of the sample is put in the bottom left corner of the paper and is then placed in the first solvent.
  2. Once the 1st chromatography is finished, the paper is turned 90 degrees clockwise, and placed in a second solvent.
  3. The different spots can then be analysed based on their Rf values in both of the solvents.
2D chromatography

RF VALUES

The Rf value is a ratio of the distance travelled by the solute and the distance moved by the solvent.

Rf (retention factor) formula

ELECTROPHORESIS

Electrophoresis is another technique that can be used to separate and identify proteins and/or amino acids based on their Isoelectric point (pI). Electrophoresis uses a gel or paper soaked in a buffer solution to separate the amino acids. At the buffer pH (usually 6), some amino acids will form positive or negative ions based on their isoelectric points. These ions are then attracted to the electrodes in the electrophoresis setup.

Electrophoresis can either be done using paper or a semi-firm gel. The samples to be tested are applied in the centre of a piece of paper or in a cavity in the gel. An electric field is applied over the gel or paper. Due to the electric field, the proteins and amino acids will seperate.

METHOD

Paper electrophoresis
Electrophoresis

FACTORS AFFECTING SEPARATION

The separation of the amino acids and proteins depends on how they interact with the gel or the paper and solvent. This can be affected by:

  • The molecular weight (size) of the protein or amino acids
    • A a small, light amino acid like Lysine will interact less than a large protein like an enzyme
  • The shape of the protein or amino acid (e.g. tertiary structure)
    • This is similar to molecular weight in that a bigger protein will interact more than a small, ‘streamlined’ amino acid.
  • The charge/s on a protein or amino acid
    • The separation in electrophoresis is based on electric charge and the molecules attraction to the + and – of the electrophoresis setup. If the charge is bigger, the attraction will be bigger and the amino acid or protein will travel further.

NATIVE AND DENATURING ELECTROPHORESIS

NATIVE ELECTROPHORESIS

  • Enzymes and proteins are in their natural form
  • Separation in electrophoresis is therefore based on their size AND shape

DENATURING ELECTROPHORESIS

  • Sample is chemically or thermally denatured
    • This is done to break the intramolecular forces ‘within’ the proteins so that they have not tertiary structure. The protein chains are linearized.
  • Separation in electrophoresis is therefore based on their size ONLY

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