Membrane lipids II

phospholipases cleave specific bonds in … creating a variety of free products including … (name 4)

phospholipids, free fatty acids, lysophospholipids, DAG and phosphatidic acid

many products of phospholipases act as … … and participate in signalling pathways influencing processes like … (name 3)

second messengers, cell growth, stress response and inflammation

PLA1 cleaves the … … bond at the … position

PLA2 cleaves the … … bond at the … position

PLC cleaves the … bond … the phosphate, releasing … and …

PLD cleaves the … bond … the phosphate, releasing … and …

acyl ester, sn1

acyl ester, sn2

phosphodiester, before, base P and DAG

phosphodiester, after, base and phosphatidic acid

the outer monolayer is rich in lipids such as … and …

the inner monolayer is rich in lipids such as … and …

phosphatidylcholine and sphingomyelin

phosphatidylethanolamine and phosphatidylserine

sphingomyelin components

ceramide, phosphate and choline

ganglioside components

ceramide, oligosaccharide and sialic acid

cis and trans FAs are …

enantiomers

PKC is a … and … kinase

serine and threonine

molecular PKC roles

1. receptor …

2. regulation of …

1. desensitization

2. transcription

physiological roles of PKC

1. modulation of … …

2. regulation of … …

3. … and …

1. immune responses

2. cell growth

3. learning and memory

3 PKC isozymes

conventional, novel and atypical

what do the following require for activation

1. conventional PKC isozymes

2. novel PKC isozymes

3. atypical PKC isozymes

1. DAG and calcium

2. only DAG

3. neither

PLA2 releases … acid from membranes and is categorised in terms of … and association with …

arachidonic, localisation, calcium

FAs at sn1 are usually …

FAs at sn2 are usually …

saturated

unsaturated

3 isozymes of PLA2

1. secretory

2. calcium independent

3. cytosolic

secretory PLA2

1. originally studied from … and … venom

2. requires … for activity

3. … groups at least

4. … is primarily implicated in … …

5. found … especially in … tissue

6. … PLA2 important in … function

7. released by … and causes lysis of gram … bacteria

1. bee and snake

2. calcium

3. 10

4. PLA2 IIA, rheumatoid arthritis

5. extracellularly, damaged

6. pancreatic, digestive

7. macrophages, positive

Ca²⁺ independent PLA2

1. found in the …

2. maintenance of … through … of membrane …

3. involvement in … and … …

1. cytoplasm

2. homeostasis, remodelling, phospholipids

3. apoptosis and muscle contraction

cytosolic PLA2

1. … bound … PLA2

2. translocates to the … membranes, cleaves … and releases … acid

1. calcium, phosphorylated

2. intracellular, phospholipids, arachidonic

PLA2 mediated intracellular signalling and inflammation

1. intracellular … levels rise

2. 2 … binds to the … domain of PLA2, exposing … residues

3. … domain interacts with and sticks to … rich perinuclear membrane

4. … domain also adopts a conformation where it can be … as its … residues form a pocket to bind … chains

5. … adds a phosphate at … for deeper penetration and binding to … by the … domain

6. … domain also interacts with …

7. … adds a second phosphate at … for maximal activation

8. PLA2 hydrolyses the … bond at … and releases … acid

9. … acid is then metabolised by … and … enyzmes into …

1. calcium

2. calciums, C2, hydrophobic

3. C2, PC

4. catalytic, activated, hydrophobic, acyl

5. MAPK, Ser505, PIP2, catalytic

6. C2, ceramide 1 phosphate

7. MAPKAPK, Ser727

8. ester, sn2, arachidonic

9. arachidonic, COX and LOX, eicosanoids

AA functions

1. activates … …

2. activates …

3. precursor of many … molecules like …

1. ion channels

2. PKC

3. signalling, eicosanoids

what are eicosanoids cruicial in?

fever, inflammation, pain and immunity

3 examples of eicosanoids made from AA

3 examples of eicosanoids made from DHA

prostaglandins, thromboxanes and leukotrienes

resolvins, protectins and maresins

DHA information

1. omega … FA

2. highly abundant in the … and …

3. changes … … and affects … and … … function

4. enchances … and … formation

5. serves as an … and … precursor

1. 3

2. brain and retina

3. membrane fluidity, receptor and ion channel

4. neurotransmission and synapse

5. antioxidant and anti inflammatory

AA can be converted to … which is an endogenous ligand for … receptors

anandamide, cannabinoid

AA is highly … and … meaning it can cross the … and act on … cells (it is also a … messenger in …)

reactive, liposoluble, membrane, neighbouring, retrograde, neurons

AA’s double bonds mean it is a target for … enzymes

oxygenase

drug which acts as a leukotriene receptor antagonist

montelukast

what does NSAIDs stand for?

nonsteroidal anti inflammatory drugs

does aspirin only inhibit COX1 or COX2?

both

does ibuprofen only inhibit COX1 or COX2?

both

example of steroidal drugs which inhibits PLA2

corticosteroids

phospholipases and membrane curvature

phospholipases can induce or modulate membrane curvature and tension by breaking down phospholipids asymmetrically which is important for membrane fusion, vesicle formation and protein insertion

COX1 info

1. … expressed

2. induces both … and …

3. is synthesised in … states

4. maintenance of …

5. involved in proper … and … functions

1. constitutively

2. prostaglandins and thromboxanes

3. basal

4. homeostasis

5. kidney and gastric

COX2 functions

1. it is … and stimulated by … mediators such as …

2. induces production of …

3. is associated with …, … and …

4. highly expressed in … and …

1. inducible, inflammatory, cytokines

2. prostaglandins

3. inflammation, pain and fever

4. macrophages and leukocytes

prostaglandins immediate and long term effects

1. vasodilation

2. decreased plateled aggregation

3. renal homeostasis (COX1)

4. decreased nociceptor treshlod (COX2)

thromboxanes immediate and long term effects

1. vasoconstriction

2. increased platelet aggregation

DHA is synthesized in the … but essential sources during development are … …

liver, maternal reservoirs

DHA is absorbed in the …

it travels in the blood either as a … … or in conjugates with … bound to … and …

it is liberated in the … and incorporated into the … system

intestine

free FA, TAGs, LDL and albumin

BBB, nervous

in plasma membranes, DHA cycles in an out of … and … … depending on … … needs

phospholipids and internal reservoirs, dynamic cellular

by affecting membrane fluidity DHA affects functions implicated with the plasma membrane such as … (list 5)

1. drug permeability

2. transport

3. activity of membrane bound proteins

4. neurotransmission

5. cardiovascular function

AA is a marker of … …

DHA is a marker of … … and acts as an … as it increases the synthesis of …

oxidative stress

oxidative protection, antioxidant, reductases

a … is any projection or extension than emerges from the cell body of a …

neurite, neuron

DHA can be converted into resolvins, protectins and maresins which inhibit … … of … and … …

transendothelial migration of neutrophils and cytokine production

repeat DHA and NF-kB signalling

ok

molecular effects of DHA in cognition

1. increases expression of … receptors in …

2. promotes … expression of …

1. glutamate, hippocampus

2. synaptic, synapsin

biological effects of DHA in cognition

1. increases … …

2. promotes …

3. in vitro promotes the differentiation of … … cells into …

1. neurite outgrowth

2. synaptogenesis

3. neural stem, neurons

the decrease in cognition with age correlates with the decrease in … levels

DHA

DHA improves … …, … and … … in hippocampus of aged rats

spatial learning, LTP and NT release

fatty acid … influences membrane … and …

saturation, rigidity and fluidity

if the R group is an H what molecule is formed?

and if the R group is phosphocholine or phosphoethanolamine?

ceramide

sphingomyelin

cholesterol … influences membrane … and …

density, rigidity and fluidity

what does cholesterol do to fluid regions of the membrane?

stiffens them

what does cholesterol do in ordered regions of the membrane?

prevents crystallization

cholesterol presents at near 1:1 ratio with … in … plasma membranes

phospholipids, mammalian

raising the cholesterol content in lipid bilayers consistently stiffens membranes by increasing their … … and decreasing their … to …

bending rigidity, capacity to deform