Molecular basis of health, disease and therapeutics Flashcards
Alternative term for ‘cause’ of disease
aetiology
Alternative term for ‘progression’ of disease
pathogenesis
Example of oral health having consequences on other body systems
Full mouth debridement in CVD patients can increase the risk of a heart attack
Function of cell signalling pathways
enable cells to detect and respond to changes in the environment
Name of the chemical signals involved in cell signalling
ligands
What are the 4 categories of chemical signalling?
Paracrine, autocrine, endocrine, contact-dependent signalling (depends on distance ligand needs to travel)
What does paracrine chemical signalling involve?
A localised response in which a cell targets a different cell nearby.
What does endocrine chemical signalling involve?
A cell targeting a distance cell through the bloodstream.
What does autocrine chemical signalling involve?
A cell targets itself / same type of cell.
What does contact-dependent chemical signalling involve?
A cell targeting a cell connected by gap junctions.
How do cells recognise signals?
The target cells will have complementary receptors to the ligands.
2 possible locations for receptors on the target cell
cell-surface receptors or intracellular receptors
Which ligands will bind to cell-surface receptors?
Large and hydrophilic ligands (majority) as plasma membrane is impermeable
Which ligands will bind to intracellular receptors?
some small, hydrophobic ligands / molecules
What are the 3 distinct stages of cell communication?
- receptor ligation
- signal transduction
- cell response
What does receptor ligation involve?
ligand binds to the complementary receptor causing the intracellular domain to change shape. This sets off a chain of biochemical reactions.
What does signal transduction involve?
A chain of biochemical reactions / signal transduction cascades delivers the message to the effector proteins
What does the cell response involve?
Effector proteins carry out a response
What is meant by receptor ligation being highly specific?
one ligand binds to one (or a few) receptors. one receptor binds to one (or a few) ligands.
Example of high specificity of receptors
adrenergic receptors will only bind adrenaline or noradrenaline
What are the 3 classes of membrane receptors?
G-protein coupled receptors, enzyme-linked receptors, ion channel receptors
Which is the largest and most diverse group of membrane receptors?
GPCRs (G-protein coupled receptors) - up to 1000 different GPCRs
Mode of action of G-protein coupled receptors
Interact with G-proteins (GDP - guanosine diphosphate) and activate them (GTP). Active G-proteins (GTP) activate cell membrane proteins (e.g. adenyl cyclase -> cAMP)
Example of a drug that target GPCRs
Beta blockers switch off the GPCR pathway
Which class of receptors have intrinsic enzyme activity?
Enzyme-coupled receptors
Which class of receptors have an important role in regulating cell growth, differentiation and survival?
Enzyme-coupled receptors
What is the largest family of enzyme-coupled receptors?
Receptor Tyrosine Kinases (RTKs)
Mode of action of Receptor Tyrosine Kinases
When the ligand binds, the receptor binds other proteins at low concentrations and phosphorylates them (adds PO4). These proteins affect gene transcription.
Which class of receptor is important in neuronal and muscular action potentials?
Ion channels
2 types of ion channels
ligand-gates and voltage-gated ion channels
Function of ion channels
convert chemical messages into electrical signals (e.g. ACh binds to ligand-gated channels causing them to open which allows an influx of Na+)
Example of drug that blocks voltage-gated Na+ channels
lidocaine (local anaesthetic)
Function of signal transduction
amplifies the signal (e.g. Ca2+ released from SR) and delivers the signal to effector proteins
Features of the signal transduction cascade
second messengers, phosphorylation, action potentials
What are second messengers?
small-non protein molecules (e.g. cAMP and Ca2+)
How is cAMP produced?
ATP is converted to cAMP by activated adenyl cyclase (can be activated by GPCRs)
Function of cAMP
A second messenger than activates protein kinase A which can phosphorylate transcription factors resulting in changes in gene expression.
Role of phosphorylation in the signal transduction cascade
Protein kinase A (PKA) (activated by cAMP) phosphorylates transcription factors which can switch them on or off (modifies protein activity). This changes gene expression.
Example of the final target molecule
transcription factor (binds to DNA to regulate gene transcription)
What is a key cause of disease?
A breakdown in cellular communication
Examples of malfunctions that can cause a breakdown in cell communication and therefore disease
loss of signal, failure to respond to signal, failure of signal to reach target, over/under expression of signal, multiple breakdowns.
Example of a disease caused by the loss of the signal
type 1 diabetes
Example of a disease caused by cells failing to respond to a signal
type 2 diabetes
Example of a disease caused by the failure of a signal to reach the target cell
MS, neurodegenerative diseases, spinal cord injury
Example of disease caused by over/under expression of signal
hyper/hypothyroidism
Example of disease caused by multiple breakdowns in cell communication
cancer - DNA not repaired, cell divides without signal to, cells don’t stay within boundaries, doesn’t respond to apoptosis signals
Why is type 1 diabetes caused by a loss of the signal?
Beta cells are destroyed by autoimmune disease so no insulin is released. Therefore no ligand binds to receptors on the target cell so there is no glucose uptake into the muscle and liver cells leading to harmful glucose accumulation in the blood.
How does injecting insulin treat diabetes?
Insulin is available and binds to receptors on target cells. The signal is transduced and the cell responds by up taking glucose.
Is injecting insulin a cure for type 1 diabetes?
No because the insulin targets the consequence of the disease. Autoimmune T and B cells are still circulating.
How can further beta cell destruction be limited in type 1 diabetes?
Patients can take immune modifying drugs
Why is type 2 diabetes caused by the failure to respond to the signal?
Insulin binds to the receptor; however, it is desensitised. Signal transduction is not activated so no glucose is uptaken into the cell.
Treatment for type 2 diabetes
diet and exercise, metformin
How does metformin treat type 2 diabetes?
The insulin receptor is RTK. Metformin inhibits tyrosine phosphatase (removal of PO4) which prevents the switching off of receptors. Metformin also increases insulin receptor expression.
Treatment for multiple sclerosis symptoms
steroids and immune-modifying drugs prevent autoimmune destruction of myelin sheaths
Which molecular basis that breaks down in periodontitis?
overexpression of the signal - causes uncoupled bone formation and bone resorption (osteoclasts are more active than osteoblasts)
Treatments for cancer
surgery, chemotherapy, radiotherapy, immune therapy, vaccines
What is chemotherapy?
The systemic administration of one or more anti-cancer drugs that target rapidly proliferating cells (including hair)
What is radiotherapy?
Using radiation to damage DNA in cancer cells which is guided by imaging. (non-specific so also kills healthy cells)
What is immune therapy?
using monoclonal antibodies to aid the immune system in recognising and killing faulty cells
Example of vaccine used to prevent cancer?
HPV are DNA tumour viruses that cause cervical cancer. HPV vaccine has eliminated almost all cervical cancer.
