Activation and Inhibition of Proteins #1

Question 1

What are the four steps for activation and inhibition of proteins?

Answer 1

1. Chemical substance
   - travels from its source (many different ways)
2. Binds to protein
   - chemical substances interacts with its target protein, often called binding or reception
3. Causes activation or inhibition
   - binding event affects the protein to either activate or inhibit it
4. Changes cellular response
   - this leads to functional consequences that change the cellular response

Question 2

Define receptor

Answer 2

A cellular protein (or assembly of proteins) that control chemical signalling between and within cells
- these control many important physiological processes (including some of the senses)

Question 3

Compare enzymes and receptors

Answer 3

Enzymes:
- Generally one active site
- Binds SUBSTRATES
- Changes substrate into product
- Can be membrane bound or free in cytosol

Receptors:
- Can have several binding sites
- Bind LIGANDS
- Release ligand unchanged
- Can be membrane bound or free in cytosol

Both can be activated or inhibited, and used as drug targets

Question 4

What are the receptor classes?

Answer 4

1. Ligand-gated ion channel
2. G protein-coupled receptor (GPCR)
3. Receptor tyrosine kinase (RTK)

They have different structures
The same overall steps of activation and inhibition occur for all receptors, though the exact details differ

Question 5

Describe step 1, chemical substances

Answer 5

• Ligands are very diverse in chemical structure, ranging from small molecules to large peptides and even proteins
• There are endogenous ligands that are produced in the body
• Drugs and toxins are examples of exogenous ligands
• All ligands make chemical contact with their specific receptors

Question 6

Define ligand

Answer 6

The general term given to a chemical substance that specifically binds to a receptor. Includes both agonists and antagonists.

Question 7

Describe step 2, binding to receptor proteins

Answer 7

• Most receptors are found on the outer cell membrane, where they act as sensors of the extracellular environement
• Ligand does not usually have to pass through the membrane
• The binding of the ligand to the receptor is the FIRST step in the process of receptor activation
• The receptor is a ‘gate-keeper’ of cellular activity, controlling it from the cell surface
• Intracellular responses to extracellular signals can be produced by a membrane receptor being activated

Question 8

Describe the specificity of binding to receptor proteins and how this relates to drugs

Answer 8

• There is specificity between ligands and receptors
• Activation and inhibition will happen only when this pairing is correct
• Size and shape of the ligand must match the corresponding receptor of the ‘binding pocket’ allowing enough chemical interacting for binding to occur
  (similar to the ‘lock and key’ concept we learnt about for enzymes)
• This mechanism is used to make drugs that bind only to certain receptor targets.
  Chemists often start with the chemical structure of an endogenous ligand, making new molecules from this to produce Sade and effective medicines

Question 9

Describe step 3 and 4 for activation

Answer 9

Step 3.
- A chemical substance (ligand) that binds to a receptor and activates it is called an agonist
- Receptor undergoes a conformational change to become activated

Step 4.
- Active receptor starts a chain of events where messages are passion on through the cell bia a process called signal transduction
- Different receptors use different types of relay molecule to pass on messages

Question 10

Describe step 3 and 4 for inhibition

Answer 10

Step 3.
- A chemical substance (ligand) that binds to a receptor and prevents activation by an agonist is called an antagonist
- Agntagonits binds and blocks against agonist binding, receptor remains inactive

Step 4.
- signal transduction does not occur