Lipid signaling Flashcards
most basic phospholipid
phosphatidic acid - phosphate, glycerol, two nonpolar tails
why do lipid molecules aggregate in solution
hydrophobic effect, nonpolar tail of each lipid molecule surrounded by ordered molecules which are released upon aggregation. So driven by entropy.
three types of aggregating lipid structures formed in aqueous solution
micelle, bilayer, liposome (resembles cellular architecture)
another name for liposomes
nanoparticles
functions of membrane lipids
- principle barrier for cell
- Mediate cell-cell interactions
- Serve as second messengers
- Affect membrane protein activities
how is lipid signaling regulated?
- Substrate availability
- Lipid kinases (alteration of their intrinsic activity)
- Lipid phosphatases
- Membrane localization (ex “interfacial activation”)
T/F. Composition of cell membrane lipids is similar for both outer and inner monolayer
False, asymmetry both prevalent and important
Which lipid can famously move freely between leaflets?
Diacylglycerol (DAG)
what is the major diff between lipid-mediated signaling and other signaling systems?
Lipids are hydrophobic, therefore their generation, effect and metabolism must involve hydrophobic environment or at least be amphipathic
Name some examples of lipid signaling functions
DAG (activates protein signaling mediators), IP3 (elevates intracellular Ca2+), Ptdins(2,4,5)P3 (activates PDK/AKT), Sphingosine-P (stimulates growth - receptor mediated), ceramide (apoptosis)
three major types of lipid metabolizing signaling enzymes
phospholipases (PLA2), lipid kinases (DAG kinase), and lipid phosphatases (PTEN)
soluble kinetics vs interfacial kinetics
interfacial works through mediator, more difficult to study than soluble
two conceptual modes for interfacial enzyme catalysis
scooting mode, hopping mode
cleavage products of different phospholipases
- PLA2 : phospholipid —-> LysoPL and free fatty acid
- PLC : removes head group and PO43-, makes DAG
- PLD: just removes head group, makes phosphatidic acid
4 major types of PLA2
- Small secreted
- Cytosolic – regulated by Ca and phosphorylation (can be activated therefore by PLCs, see below).
Ca-independent - PAF acetylhydrolases (act on platelet activating factor (PAF)).
- This specific PLA2 helps degrade PAF; hydrolyzes acetyl group.
- PAF is very potent => this phospholipase is important in regulating levels
T/F. After PLA2 cleavage, both products are released from the membrane
False, they remain embedded in the membrane
eiconoids are derived from
arachidonic acids, proken down by PLA2
phosphatidylinositol cycle (PI cycle)
PI to PIP to PIP2, generates IP3 and DAG, IP3 increases calcium, PIP2 stimulates DAG which is endogenous activator of PKC and leads to growth and proliferation
What is the min number (and identity) of signaling molecules generated by the PI cycle after activation of the PI-PLC only?
Two - IP3 (water soluble) and DAG (hydrophobic)
What do PLCs do?
Hydrolyze PIP2 to generate IP3 and DAG, three major classes that are activated by different mechanisms
What is one way you could prove interfacial activation was occuring in your enzyme?
Add weak and strong detergent vs. no detergent. In presence of strong detergent (think about micelle structure), you have an increase in the lipid environment => more enzyme activity.
What kinase can phosphorylate PIP2, and what is the product of this phosphorylation?
PI3 kinase, makes PIP3
Why is PIP3 an important signaling molecule?
It activates PDK, which phosphorylates and activates AKB (also known as PKB). PDK and AKB are brought by PIP3 to the membrane surface, and then AKB goes forth and activates other junk like mTOR, this activity very important for growth
What is PTENs activity?
PTEN is a phosphatase, catalyzes PIP3 —-> PIP2, considered a tumor suppressor
