Lipids in the cell membrane Flashcards
what are eicosaniods
- inflammatory mediators, they are released from cells and act on other cells
- they are considered local hormones
- They have specific effects on target cells close to
their site of formation (autocrine/paracrine). - They are rapidly degraded, so they are not transported to distal sites within the body.
what is step one of cell to cell communication
synthesis of signal
what is step two of cell to cell communication
release of the signalling molecules by the signalling cell: exocytosis, diffusion, cell-cell contact
what is step three of cell to cell communication
transport of the signal to the target cell
what is step four of cell to cell communication
detection of the signal by a specific receptor protein
what is step five of cell to cell communication
a change in cellular metabolism, function or development triggered by the receptor-signal complex
what is step six of cell to cell communication
removal of the signal or densensitisation
transport of signals
can act at short or long-range. in animals, signalling by extracellular molecules can be classified into different types
long range
endocrine: hormone released by endocrine ell and carried in the bloodstream to distal target cells
example of a long-range hormone
FSH from pituitary to ovary
short range
- neurotransmission (synapses)
- paracrine (signalling molecules only effect target cells in close proximity to secreting cells
- autocrine (cells respond to substances that they themselves release
- membrane bound proteins can interact to signal
examples fo short range
breathing - the phrenic and thoracic nerves send impulses from the brain to the diaphragm
somatostatin release by pancreas cells acts locally
neurotransmitters and growth factors bind to the cells that release them
signalling by T cells in the immune system
give me an example of multiple types of signalling occurring simultaneously
insulin being released from the pancreatic beta cells acts in an autocrine, a paracrine and an endocrine manner
what is signal transduction
Many signalling molecules that affect cell activity or function do not enter cells.
• They act on membrane-bound receptors that control the production of intracellular chemicals (second messengers).
• These mediate cell activity.
• Exception is lipid soluble signalling molecules (bind intracellular receptors)
inositol phospholipid signalling
The G protein activates the PLC to then liberate to PIP2 molecules known as DAG and IP3
by what action does calcium activates cellular pathways
Calcium concentration transiently increases in the cell in response to IP3 release Calcium binds to proteins to regulate their function
Give me an example of calcium activating cellular pathways
: Ca2+/Calmodulin - activates proteins/enzymes through direct interaction (e.g. myosin light chain kinase, which regulates smooth muscle contraction)
substrates for PKC’S and their actions
tumour suppressor p53 (transcription factor) → prevents tumour formation
CaV 1.2 (calcium channel) → heart muscle contraction
IKKα (cytokine) → B cell activation (immune function)
what is the initial rate-limiting step in eicosanoid synthesis
the liberation of arachidonic acid by phospholipase A2 (PLA2)
what is PLA2 activated by
a variety of receptor-mediated signals.
Arachidonic acid can be metabolised by
(a) cyclo-oxygenase and peroxidase to give prostaglandins and thromboxanes
(b) lipoxygenases to give leukotrienes.
what is the receptor for vasoconstriction
EP1 receptor
What is the receptor for vasodilation
EP2 receptor
prostaglandins =
eicosanoids
Thromboxanes
- Synthesised in platelets (clotting)
- Short-lived (autocrine/paracrine)
- Thromboxane A2 (TXA2) has prothrombotic properties
- Stimulate platelet aggregation
- Vasoconstrictor
Leukotrienes
- synthesised in white blood cells
- conjugated system of double bonds
- Some contain the amino acid cysteine in their structure (anaphylactic shock)
- used in immune response
heavily implicated in asthma and allergy
Platelet-activating factor
- By-product of arachidonic acid liberation
- Synthesised in leukocytes (platelets, neutrophils, basophils)
- Also synthesised by injured tissue (e.g. endothelial cells)
- Platelet aggregation
- Vasoconstriction
- Inflammation
- Immune response (also anaphylaxis)
NSAIDs
Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and derivatives of ibuprofen, inhibit cyclooxygenases.
They inhibit formation of prostaglandins involved in fever, pain, & inflammation.
They inhibit blood clotting by blocking thromboxane formation in blood platelets.
Ibuprofen and related compounds block the hydrophobic channel by which arachidonate enters the cyclooxygenase active site.
Actions of aspirin
acetylates a serine hydroxyl group near the active site, preventing arachidonate binding.
The inhibition by aspirin is irreversible.
However, in most body cells re-synthesis of Cox-1 would restore cyclooxygenase activity.
Aspirin as an anticoagulant
Thromboxane A2 stimulates blood platelet aggregation, essential to the role of platelets in blood clotting.
- Many people take a daily aspirin for its anti- clotting effect, attributed to inhibition of thromboxane formation (via COX-1 inhibition) in blood platelets.
- This effect of aspirin is long-lived because platelets lack a nucleus and do not make new enzyme.
