L20: Genomics & Pharmacology Flashcards
How to clone a receptor gene?
1) Extract mRNA from brain
2) Convert it into cDNA
3) Amplify cDNA with PCR to separate
4) Screen it with ligand
5) Activate it with a Hit!, then sequence it
How many genes are estimated to be present in the whole human genome?
2100
Which type of receptor is characterized by having seven transmembrane domains (TMDs)?
G-protein coupled receptors
What is a key feature of G-protein coupled receptors (GPCRs)?
They are a large and diverse family of receptors
Which class of receptors does the muscarinic ACh receptor belong to?
GPCR
Features of mucarinic ACh receptor
1) Single protein
2) 1 ACh binding site
3) 7 transmembrane domain
4) GPCR region site
Features of nicotinic ACh receptor
1) 5 protein subunnits
2) 2 ACh binding site
3) 4 transmembrane domains
4) Ion pore (cation)
How does the GPCR receptor work?
1) Activate another protein, G-protein
2) Activation changes ACh binding
3) Changes shape of receptor
4) Binds to G-protein & activates it
5) alpha & beta-subunit leaves
What does the 5 subunits in M1 muscarinic ACh receptor allow?
Allow different subtypes using the same neurotransmitter to activate differnt signalling pathways
What protein targets can be molecular targets for drugs
1) GPCR
2) Enzymes
3) Ion channels
4) Transporters
5)
Similarities of muscarinic ACh receptor & nicotinic ACh receptor
1) Both bind ACh
2) Involved in neurotransmission
3) Role in ANS
4) Target for important drugs
Class A receptors
1) Muscarinic receptor
What are orphan receptors?
Lost their ligand
Define pharmacogenomics
Genetic differences influence drug effectiveness & toxicity
What is halothane?
General anaesthetic
What does halothane releasing Ca2+ into skeletal muscle activate?
Mutations in the SR calcium release channel
What can gene screening predict?
Drug responses & reduce side effects
What genetic mutation can affect the effectiveness of succinylcholine?
A mutation in the gene coding for plasma cholinesterase
How do GPCRs contribute to cellular signaling and drug targeting?
1) Initiate cell signals upon ligand binding
2) Activate intracellular signalling pathways
What are the potential benefits and risks of using gene therapy in treating genetic disorders?
Benefits:
- Cure genetic disorders
- Replace faulty genes
Risks:
- Gene disruption
- Uncontrolled gene expression
- Incorrect cell targeting
What is an orphan receptor in pharmacology?
A receptor whose endogenous ligand is unknown
What is the relationship between amino acid sequence and protein function in drug targets?
The amino acid sequence determines the protein’s structure and function
What is the role of pharmacogenomics in personalized medicine?
To optimize drug selection and dosage based on genetic makeup
What challenges are associated with gene therapy?
Challenges in controlling the new gene’s expression
