Block A Lecture 3 - Lipid Signalling Flashcards
State 5 functions of the cell membrane?
Answers include:
A barrier between intra and extracellular environment
Functions in signal transduction and transport
Ion and chemical gradients
Rigidity and shape
Compartmentalisation and specialisation (resulting in greater efficiency)
Functions of specialised complex internal membrane structures
(Slide 3)
How many molecules thick is a membrane?
2 (~4 nm thick)
(Slide 4)
Lipids are amphipathic - what does this mean?
It contains both hydrophilic and hydrophobic parts
(Slide 4)
Despite lipids being amphipathic - is the majority of the membrane hydrophobic or hydrophillic?
Hydrophobic
(Slide 4)
What is a cell membrane held together by?
Weak non-covalent interactions - such as L.D.FS are hydrogen bonding
(Slide 4)
Are membranes fluid or rigid?
Fluid
(Slide 4)
Are membranes symmetrical?
No
(Slide 4)
What does isotropic and anisotropic mean?
Isotropic means forces between molecules extend in all directions.
Anisotropic is the opposite.
(Slides 5 and 6)
What is the hydrophobic effect?
The fact that water molecules exchange hydrogen bonds with neighbours at a rate of 10^11 s-1
(Slide 6)
How does the hydrophobic effect arise?
It arises from a peculiarity of water structure
(Slide 6)
Why does an interface between water and a non hydrogen bonding group (such as CH3) result in water molecules having fewer opportunities for hydrogen bond exchange?
As forces are anisotropic, so there are less areas for exchange to occur - (the water is rotationally and translationally constrained)
(Slide 6)
What 2 effects does having an interface between water molecules and a non hydrogen bonding group (such as CH3) have?
An ice-like state forms at the interface, and this creates a subsequent decrease in entropy
(Slide 6)
Regarding the hydrophobic effect, how do you arrange water in order to get an increase in entropy?
Any situation which minimises the area of contact between water and non polar (hydrocarbon) regions of proteins - such as by clustering non polar groups together
(Slide 6)
What are 5 examples of lipid classes (as outlined by the international lipid classification and nomenclature committee)?
Fatty acids
Glycerophospholipids
Sphingolipids
Glycerolipids
Sterols
(Slide 8)
What are the 3 types of membrane lipids?
Phospholipids
Glycolipids
Cholesterol
(Slide 9)
Where are the majority of membrane lipids synthesised?
In the endoplasmic reticulum (ER)
(Slide 9)
What do phospholipids form as a consequence of the hydrophobic effect?
Vesicles
(Slide 11)
What are 4 reasons that the phospholipid bilayer’s asymmetry is important?
- Phosphatidylinositol - key signalling molecule on the inside of the plasma membrane
- During apoptosis a phosphatidylserine specific flippase is activated, revealing this lipid on the surface of the dying cell which is then recognised by macrophages which then consume the corpse
- Blood platelets sequester (hide) phosphatidylserine (PS) in the cytoplasmic leaflet of their plasma membrane, but when activated in response to blood vessel injury, they scramble the lipids in the 2 leaflets of the membrane to expose PS at the cell surface where it functions as an essential cofactor in the conversion of coagulation proteins into a blood clot
- It can influence protein targeting, sorting and function
(Slide 13)
What is the study of lipids called?
Lipidomics
(Slide 16)
What are 4 functions of lipids?
- They function as an essential structural component of membranes
- They function as signalling molecules
- They function as “chemical identifiers” of specific intracellular components
- They function as intracellular energy stores
(Slide 17)
What is a phospholipase?
An enzyme which converts phospholipids into fatty acids and other lipophillic substances via hydrolysis
(Slide 19)
What may occur as a result of a lipid being hydrolysed by a phospholipase enzyme?
They are moved from the membrane which may result in the structure, integrity and fluidity of the membrane being altered
(Slide 19)
What happens in some cases when a lipid is hydrolysed?
A chemical moiety derived from the lipid is released from the membrane and acts as a signalling molecule
(Slide 19)
Are phospholipases diverse or conserved in their site of hydrolysis?
Diverse
(Slide 20)
What is the function of phospholipase A2?
It has a major role in signal transduction and it releases arachidonic acid
(Slide 22)
What is the formula for arachidonic acid?
C20H32O2 (4 double carbon bonds)
(Slide 22)
What 3 molecules does phospholipase A2 serve as a precursor in the biosynthesis of?
Prostaglandins
Thromboxane
Leukotrienes
(Slide 22)
Are prostaglandins locally, or systemically active?
They are locally active - either paracrine or autocrine (acting on the same cell which it is synthesised from)
(Slide 23)
Are prostaglandins potent?
Yes
(Slide 23)
Do prostaglandins have a short or long half life before being inactivated / excreted?
Short
(Slide 23)
How many known prostaglandins receptors exist?
9 receptors
(Slide 23)
What receptors do prostaglandins act on?
A subfamily of cell surface receptors called seven-transmembrane receptors
(Slide 23)
What kind of receptors are seven-transmembrane receptors?
GPCRs
(Slide 23)
What are 5 functions / actions which prostaglandins have?
Answers Include:
Dilate vascular smooth muscle cells (lowering blood pressure)
Facilitate platelet aggregation
Sensitise spinal neurons to pain
Constrict smooth muscle
Regulate inflammatory processes
Regulate Calcium Movement
(Slide 25)
What is thromboxane?
A vasoconstrictor and potent hypertensive agent which facilitates platelet aggregation.
(Slide 26)
What is a homeostatic balance?
The body’s ability to maintain a stable internal environment despite changes in external conditions
(Slide 26)
Where and what is thromboxane in a homeostatic balance in?
It is in a homeostatic balance with prostacyclin, in the circulatory system
(Slide 26)
What do leukotrienes do?
They stimulate proinflammatory actives such as endothelial cell adherence and chemokine production by mast cell. They also can induce asthma and other inflammatory disorders resulting in a reduced airflow to the alveoli
(Slide 26)
What is the endocannabinoid system (ECS)?
An important neuromodulatory system
(Slide 30)
What 3 things is he endocannabinoid system (ECS) composed of?
Cannabinoid receptors, endogenous cannabinoids (known as endocannabinoids), and the enzymes responsible for the synthesis and degradation of the endocannabinoids
(Slide 30)
What are disruptions in the endocannabinoid system (ECS) linked to?
Schizophrenia and many other conditions
(Slide 30)
What are 4 examples of cannabinoid receptors?
CB1 and CB2 receptors - these are both GPCRs
Transient receptor potential channels
Peroxisome proliferator-activated receptors
(Slide 32)
What kind of receptors are CB1 and CB2 receptors?
GPCRs
(Slide 32)
What class of G proteins do CB1 and CB2 receptors couple to?
Gi and Go
(Slide 32)
What are the functions of the endocannabinoid system?
It’s linked to appetite metabolism, pain, inflammation, sleep motor control
(Slide 33)
What receptor is rimonabant an inverse agonist of?
CB1
(Slide 33)
What purpose was rimonabant developed for?
To be an anti-obesity drug
(Slide 33)
Why are phosphoinositides important?
Are they are all inter-related (can be easily converted into each other) and they are an important part of many biological processes
Note: There’s a cycle for converting these things, we don’t need to know details only that it exists.
(Slides 34 and 35)
What is the most important family of phosphoinositides?
Phosphoinositide 3-kinases (PI3Kinases)
(Slide 37)
Phosphoinositide 3-kinases can often produce different effects even when acting in the same cell, how can this be the case?
As it is spatially and temporally regulated
(Slide 39)
How can phosphoinositide 3-kinase lead to different effects in different cells?
Through different effector complements
(Slide 39)
What domains do some cytosolic proteins have?
Domains which bind to the polar head groups of lipids which transiently (lasting for a short amount of time) exist in the cell membrane
(Slide 41)
What are the 2 mains things in which phosphoinositides are involved in?
Intracellular trafficking
Compartment / organelle identity
(Slide 44)
What are non-polar lipids (such as cholesterol) important for?
Membrane stability
(Slide 45)
Where are non-polar lipids highly concentrated in?
“Lipid rafts”
(Slide 45)
What can non-polar lipids interact with proteins to do?
To support signalling
(Slide 45)
What is a “lipid raft”?
A microdomain within the cell membrane that is enriched in certain types of lipids (like cholesterol and sphingolipids and has more elongated lipids)
(Slide 46)
What may be recruited into lipid rafts?
Different types of proteins
(Slide 46)
