Basic cell signaling 2, Protein and Drug target-17 Flashcards
(38 cards)
What is a drug?
Agent that interacts with specific target molecules in the body, thereby producing a biological effect
drug molecule interacts with a specific molecule in the biologic system that plays a regulatory role
How do drugs interact with receptors?
Drug and receptor relationship
Drugs interact with receptors by means of chemical forces or bonds
ligands (signal molecules) (durgs mimicking the ligands) bind to receptors to trigger a series of proteins, pathway, which lead to a biological response for example releasing a certain hormone
What is the drug action: receptor theory?
Many drugs act by binding to receptors where they either provoke/ stimulate or inhibit a biological response
- the endogenous ligand binds to receptor and produces an effect
- An agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same effect
- An antagonist drug is close enough in shape to bind to the receptor but not close enough to produce an effect.
It also takes up receptor space and so prevents the endogenous ligand from binding
What are the 4 kinds of protein involved as drug targets?
- Enzymes
- Carrier molecules/ Transporters
- Ion channels
- Receptors
What are Irreversible inhibitors?
Are those that bind very tightly to an enzyme and decrease its activity
examples:
Antibiotic-penicillin
Nerve agents- the deadliest of the classical chemical warfare agents
Organophosphate pesticides
Penicillin is an example of an irreversible inhibitor. Explain:
Irreversible inhibitor: bind very tightly to an enzyme to decrease its activity
Penicillin kills susceptible bacteria by specifically inhibiting the transpeptidase that catalyzes the final step in cell wall biosynthesis, the cross linking of peptidoglycan
What are reversible inhibitors?
What are the 2 types of reversible inhibitors?
Reversible inhibitors- bind temporarily to an enzyme and prevent its function
Competitive
mimics substrate and competes for active site, prevent the substrates from being transferred into products
Non competitive
alters the conformation of enzyme so active site is no longer fully functional
One example of competitive enzyme inhibitors is ACE inhibitors:
What is its function and how does it act as an competitive inhibitor?
The angiotensin converting enzyme (ACE) can convert angiotensin 1 to angiotensin 2
Angiotensin 2 is a peptide hormone that causes vasoconstriction and an increase in blood pressure
ACE inhibitors prevent ACE producing angiotensin 2 and help relax blood vessels and are used for treatment of hypertension
Captopril was the first anti hypertensive drug that acted as ACE inhibitor
Tipranavir is an example of an Non-competitive inhibitor
Explain what an non-competitive inhibitor is and how Tipranavir acts as one:
The inhibitor and substrate do not compete for the same binding site
The inhibitor acts at an allosteric site instead of the enzyme’s active site
Tipranavir is a potent non-competitive inhibitor of a protease in HIV
Tipranavir has the ability to inhibit the replication of HIV viruses that are resistant to other protease inhibitors
What are enzyme activators?
Give an example:
These molecules are often involved in the allosteric regulation of enzymes in the control of metabolic pathway
These molecules must bind to a site other than the substrate binding site for enzyme reaction to occur
Fructose 2,6-bisphosphate activates phosphofructokinase 1 and increases the rate of glycolysis in response to the hormone glucagon
What is the function of carrier molecules/ transporters?
Help transport of molecules across the membranes
Molecules translocated across membranes by binding to specific transporters
Either via facilitated diffusion (passive transport) or pumps (active transport)
What is the function of ion channels- voltage gated/ligand gated?
Control movement of ions by the opening and closing of the ion channel
For example:
Cell membrane, the phospholipid bilayers, is a hydrophobic barrier to hydrophilic and charged molecules Ca2+, K+, Na+ or Cl- ions
Ion channels provide a high conducting, hydrophilic pathway across the hydrophobic interior of the membrane for movement of ions across the membrane
Examples:
- Voltage dependent ion channels that respond to mechanical or electrical
- Ligand gated ion channels that respond to chemical stimuli
Example of a drug that you can develop to target channel ions, Calcium Antagonists, What is the function of this?
Calcium channel blockers also called calcium antagonists
Prevent calcium from entering cells of the heart and blood vessel walls
Relax and widen blood vessels by affecting the muscle cells in the arterial walls
-resulting in lower blood pressure
e.g Amlodipine
Cells contain receptors, What is function of these receptors?
What molecule binds to an receptor?
Proteins called receptors in the cells bind to signaling molecules and initiate a physiological response
- Each target cell responds to limited set of signals
- Different cells have different receptors for the sane signal
A ligand is a signal molecule that binds to a receptor
What are agonists? and what effect does it have when it binds to a receptor?
An agonist is a mimetic of the natural ligand and produces a similar biological effect as the natural ligand when it binds to the receptor
What are antagonists? and what effect does it have when it binds to a receptor?
Mimic ligands that bind to a receptor and prevent receptor activation by a natural ligand
The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy
Where are intracellular receptors and cell surface receptors found?
Intracellular receptors- found inside the cell, cytoplasm or nucleus
Cell surface receptors-found on cell membrane
What characteristic of a ligand supports its function?
The ligands of intracellular receptors are small, hydrophobic molecules since they must be able to cross the cell membrane in order to reach their receptors
for example:
the primary receptors for hydrophobic steroid hormones, such as the sex hormones, vitamin D are intracellular
What is the function of cell surface receptors?
Membrane-anchored proteins that bind to ligands on the outside surface of the cell
In this type of signaling, the ligand does not need to cross the cell membrane. So, the chemical structures of ligands are more diverse
What are the differences between a ligand in the intracellular receptor and a cell surface receptor?
Ligand in intracellular receptor is small and hydrophobic to be able to go across the membrane to reach the receptor
whereas, cell surface receptor ligands are more diverse because it does not need to go across a membrane
How do receptors form channels?
By multi-pass transmembrane proteins
opening or closing of channel triggered by binding of ligand
-Ions move through channel
What are the 3 main types of cell surface receptors?
- Ion-channel-linked receptors
- receptor forms a channel by multi-pass transmembrane proteins
- opening or closing of channel triggered by binding of ligand
- ions move through channel - G Protein-Linked Receptors
- seven pass transmembrane proteins
- ligand receptor interaction mediated by trimeric GTP binding protein (G Protein) - Enzyme-Linked Receptors
- Single-pass transmembrane proteins
- Are themselves enzymes or directly activate enzymes
- Mainly protein kinases
What are G protein couples receptors and its function? (GPCRs)
The largest and most diverse group of cell membrane receptors in eukaryotes
GPCRs play a diverse role in regulating a lot of functions and cellular response in the body
due to this they are highly sought after in drug target
fact: researchers estimate that between one-third to one-half of all marketed drugs act by binding to GPCRs
Describe the structure of GCPRs (G Protein Coupled Receptors):
7 membrane-spanning regions with their N-terminus on the exoplasmic face and C-terminus on the cytosolic face
-trimeric= 3 subunits
G proteins are heterotrimeric which is made up of 3 different subunits: an alpha, a beta and a gamma subunit
G proteins have the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP)
