molecular basis of health Flashcards
how do cells communicate?
via cell signalling pathways
what are the four categories of chemical signalling?
- paracrine
- autocrine
- endocrine
- juxtacrine
what is paracrine chemical signalling?
cell targets a nearby cell
what is autocrine chemical signalling?
cell targets itself
what is endocrine chemical signalling?
a cell targets a distant cell through the blood stream
what is juxtacrine chemical signalling?
a cell targets a cell connected by gap junctions
how do cells recognise signals?
- Cells have protein receptors that recognise and bind ligands
- Target cells must have the right receptor to bind the ligands
- Most signal molecules are large and hydrophilic and bind cell-surface receptors
- Some small hydrophobic molecules bind intracellular receptors (as they can diffuse through the plasma membrane)
what type of molecules can enter/exit cells?
hydrophobic molecules
describe the steps involved in a signalling pathways
- ligand binds to receptor
- receptor is activated
- the signal is tranduced to relay the signal
- cell response
what is key to remember about ligand-receptor interactions?
they are highly specific
what type of molecule are receptors normally?
trans-membrane proteins
what are the three classes of membrane receptors?
- G-protein coupled
- Enzyme-linked
- Ion channel
what are receptors within the cell called?
intracellular receptors
describe G protein coupled receptors
- Largest and most diverse group of membrane receptors
- Interact with G-proteins (GTP)
- Active G-proteins activate cell membrane proteins
- Up to 1000 different GPCRs- each highly specific for a particular signal
- ~34% (475) FDA approved drugs target GPCRs (Nat Rev Drug Dis, 2017)
describe enzyme-coupled receptors
- Receptor with intrinsic enzyme activity
- Receptor Tyrosine Kinases (RTKs) largest family
- Tyrosine kinases add PO4 to tyrosine
- RTKs typically bind proteins at low concentrations
- Important role in regulating cell growth, differentiation and survival
describe Ion-channel receptors
- Convert chemical messages into electrical messages
- Ligand-gated/voltage-gated
- Important in neuronal and muscular action potentials
- Lidocaine blocks voltage-gated Na2+
describe Ion-channel receptors
- Convert chemical messages into electrical messages
- Ligand-gated/voltage-gated
- Important in neuronal and muscular action potentials
- Lidocaine blocks voltage-gated Na2+
what is signal tranduction?
- Receptor ligation causes intracellular domain to change shape
- The message is delivered to inside the cell through a series of biochemical reactions
- Sets off a chain of biochemical reactions (signal transduction cascades) within the cell- Second messengers (small-non protein molecules)
- Phosphorylation (modifies protein activity)
- Action potentials (mediated by ion influx)
what are second messengers?
- cAMP is a common second messenger
- Converted from ATP by active adenylyl cyclase
- cAMP activates protein kinase A
- Effect changes in gene expression via the activation of transcription factors
what are possible cell responses?
- Ultimately cell communication leads to regulation of cellular responses
- Regulate protein translation by turning genes on or off
- Final target molecule may be a transcription factor – a protein that binds DNA to regulate gene transcription
what are examples of breakdowns in cellular communication which cause molecular disease?
Loss of the signal eg type 1 diabetes
Failure to respond to a signal eg type 2 diabetes
Failure of signal to reach target cell eg multiple sclerosis
Over/under expression of signal eg (over) periodontitis
Multiple breakdowns may occur- cancer
what is the treatment for type I diabetes?
- Replenish insulin
- Not a cure- only targets the symptoms of the disease
- Patients may also take immune-modifying drugs to limit further β-cell destruction
what is the treatment for type II diabetes?
- Diet and exercise to regulate blood glucose
- Insulin receptor is RTK
- Metformin inhibits tyrosine phosphatase
- Increases insulin receptor expression
what is the treatment for multiple sclerosis?
use of steroids and immune-modifying drugs to prevent/limit cell destruction
what happens in periodontitis to bone formation?
bone resorption exceeds bone formation
describe how cancer arises
- Despite tight controls breakdown in cell communication can lead to uncontrolled cell growth
- Often occurs in absence of signal
- Usually leads to apoptosis
- BUT if cell loses ability to respond to death signals it divides out of control
- Cancer always involves multiple breakdowns in communication
what are possible cancer treatments?
Surgery - mainstay of cancer treatment
Chemotherapy – Systemic administration of one or more anti-cancer drugs
Radiotherapy – Radiation damages DNA in cancer cells
Immune therapy – Immune system capable of recognising and killing faulty cells
Monoclonal antibodies – targeted immune therapy
Vaccines - HPV viruses are DNA tumour viruses,
Responsible for nearly all cervical cancers
describe the molecular basis of theraputics
- Drugs must interact chemically with a target to induce a therapeutic effect
- Typically through binding proteins in cell membrane to induce a cellular response
- Drugs manipulate existing cell communication pathways for therapeutic benefit
