Lipids and Cell Membranes 2 Flashcards

1
Q

How do lipids participate in cell-cell communication mechanisms?

A

by giving rise to intracellular second messengers.

They also serve as precursors for compounds that are released from cells and act on other cell types, called eicosanoids – inflammatory mediators.

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2
Q

What are the 6. steps of cell-cell communication?

A
  1. Synthesis of signal.
  2. Release of the signaling molecule by the signaling cell: exocytosis, diffusion, cell-cell contact.
  3. Transport of the signal to the target cell.
  4. Detection of the signal by a specific receptor protein
  5. A change in cellular metabolism, function or development triggered by the receptor-signal complex
  6. Removal of the signal or desensitisation
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3
Q

How can signalling by extracellular molecules be classified in animals?

A

Long range

Short range

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4
Q

What are long range extracellular signalling molecule types?

A

Endocrine: hormone released by endocrine cell and carried in bloodstream to distant target cells

Neurotransmission

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5
Q

What are short range extracellular signalling molecule types?

A

Paracrine: signaling molecules only affect target
cells in close proximity to secreting cells

Autocrine: cells respond to substances that they themselves release

Membrane-bound proteins can interact to signal

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6
Q

Provide an example of neurotransmission signalling

A

Example: Breathing – the phrenic and thoracic nerves send impulses from the brain to the diaphragm

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7
Q

Provide an example of paracrine signalling

A

Examples: somatostatin release by pancreas cells acts locally. Neurotransmission can also be considered to be a type of paracrine signaling.

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8
Q

Provide an example of autocrine signalling

A

Example: Some neurotransmitters and growth factors bind to the cells that release them.

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9
Q

Provide an example of membrane-bound proteins that can interact to signal

A

Example: signalling by T cells in the immune system

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10
Q

Provide an example of multiple types of signalling occurring simultaneously

A

Example: insulin released from pancreatic β-cells acts in an autocrine, a paracrine and an endocrine manner

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11
Q

Why is signal transduction important?

A

Many signalling molecules that affect cell activity or function do not enter cells

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12
Q

What is signal transduction?

A

Signal molecules that don’t pass through the cell membrane 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)

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13
Q

What are the two types of receptors that signalling molecules bind to?

A

Cell-surface receptors - (hydrophilic signalling molecule)

Intracellular receptors - (hydrophobic signalling molecule)

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14
Q

How long do ligand gated ion channels (inotropic receptors) take to cause cellular effects when activated?

A

Milliseconds

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15
Q

How long do G-protein-coupled receptors (metabotropic) take to cause cellular effects when activated?

A

Seconds

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16
Q

How long do kinase-linked receptors take to cause cellular effects when activated?

A

Hours

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17
Q

How long do nuclear receptors take to cause cellular effects when activated?

A

Hours

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18
Q

What is the general rule of thumb when determining the length of time it takes for a signalling molecule to cause action in relation to their intermediate functions intracellularly?

A

If the cell surface receptor protein causes an intracellular signalling pathway that directly causes altered protein function it gonna be fast (< sec to mins)

If the intracellular signalling pathway instead acts on the nucleus to cause altered protein synthesis then it gonna be slow (mins to hrs)

Either way its gonna cause altered cytoplasmic machinery and thus altered cell behaviour

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19
Q

How do lipid soluble molecules act on a cell?

A

They leave their binding protein in the plasma and enter the cell through the phospholipid bilayer

They then bind to a specific receptor in the nucleus/cytoplasm to form a messenger-receptor complex that binds to DNA

This causes a protein synthesis that leads to altered cell response

20
Q

Provide an example of the action of a lipid soluble molecule?

A

Cortisol enters the cell through the membrane and bonds with an intracellular receptor protein

This causes a conformational change that activates the receptor protein

The activated receptor-cortisol complex moves into the nucleus

The activated receptor-cortisol complex then binds to regulatory region of target gene and activates transcription

21
Q

Describe the inositol phospholipid signalling pathway

A

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a phospholipid found in the lipid bilayer.

It is the substrate of the enzyme phospholipase C (PLC).

PLC liberates two signalling molecules from PIP2; inositol 1,4,5 trisphosphate (IP3) and diacyglycerol (DAG).

22
Q

What role does calcium have in cellular pathways?

A

calcium activates cellular pathways

23
Q

How does calcium activate cellular pathways?

A

Calcium concentration transiently increases in the cell in response to IP3 release

Calcium binds to proteins to regulate their function

Example: Ca2+/Calmodulin - activates proteins/enzymes through direct interaction
(e.g. myosin light chain kinase, which regulates smooth muscle contraction)

24
Q

Whats a kinase do?

A

Adds phosphates as an enzyme

25
Q

What are some substrates of protein kinase C (PKC) ?

A

tumour suppressor p53 (transcription factor) → prevents tumour formation

CaV 1.2 (calcium channel) → heart muscle contraction

IKKα (cytokine) → B cell activation (immune function)

26
Q

What are eicosanoids (prostanoids)?

A

Inflammatory mediators

27
Q

Describe the area of action of eicosanoids (prostanoids)

A

The eicosanoids 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.
28
Q

What are some principal eicosanoids (prostanoids)?

A

PROSTAGLANDINS, THROMBOXANES & LEUKOTRIENES.

29
Q

What is the etymology of eicosanoids (prostanoids)?

A

Word eicosanoid derived from EICOSA indicating 20 carbon atom backbone and ENOIC meaning double bonds.

30
Q

What is the main source of eicosanoids (prostanoids)?

A

Main source of eicosanoids is arachidonic acid, a 20 carbon unsaturated fatty acid containing 4 double bonds (20:4).

31
Q

What is the initial and rate limiting step in eicosanoid (prostanoid) biosynthesis?

A

The initial and rate-limiting step in eicosanoid synthesis is the liberation of arachidonic acid by phospholipase A2 (PLA2)

32
Q

How is PLA2 activated?

A

by a variety of receptor-mediated signals

33
Q

What can arachidonic acid be metabolised by in eicosanoid biosynthesis?

A

(a) cyclo-oxygenase and peroxidase to give prostaglandins and thromboxanes
(b) lipoxygenases to give leukotrienes.

34
Q

What do prostaglandins do?

A

Vasoconstriction/dilation (redness, swelling and heat)

Inhibit/promote platelet aggregation

Effects depend upon receptor (e.g. EP1 receptor → vasoconstriction; EP2 receptor → vasodilation)

Inflammatory response, thermoregulation (fever) and pain

35
Q

Where can prostaglandins be found?

A

They are synthesised in all tissues and cell types

36
Q

What do thromboxanes do?

A

Short-lived (autocrine/paracrine action)

Thromboxane A2 (TXA2) has prothrombotic properties

Stimulate platelet aggregation

Vasoconstrictor

37
Q

Where can thromboxanes be found?

A

Synthesised in platelets (clotting)

38
Q

What do leukotrienes do?

A

Some contain the amino acid cysteine in their structure (anaphylactic shock)

Immune response

Heavily implicated in asthma and allergy

39
Q

Where can leukotrienes be found?

A

“Leuko” because they are synthesised in white blood cells and “trienes” because they contain a conjugated triene system of double bonds.

40
Q

What do platelet-activating factors do?

A

Platelet aggregation
Vasoconstriction
Inflammation
Immune response (also anaphylaxis)

41
Q

How are platelet-activating factors formed?

A

Not strictly an “eicosanoid”
By-product of arachidonic acid liberation
Synthesised in leukocytes (platelets, neutrophils, basophils)
Also synthesised by injured tissue (e.g. endothelial cells)

42
Q

What are NSAIDs?

A

Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and derivatives of ibuprofen, inhibit cyclooxygenases.

43
Q

What do NSAIDs do?

A

They inhibit formation of prostaglandins involved in fever, pain, & inflammation.

They inhibit blood clotting by blocking thromboxane formation in blood platelets.

44
Q

Give an example of a NSAID?

A

Ibuprofen and related compounds block the hydrophobic channel by which arachidonate enters the cyclooxygenase active site.

45
Q

What does aspirin do?

A

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.

46
Q

Describe the action of aspirin as an anticoagulant

A

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.

47
Q

How does cell calcium concentration increase?

A

Calcium concentration transiently increases in the cell in response to IP3 release