phospholipids

Question 1

2 main classes of phospholipids

Answer 1

• glycerophospholipids (glycerol backbone)

- sphingolipids (sphingosine backbone)

Question 2

4 components of glycerophospholipid

Answer 2

backbone- glycerol
Head group- variable, esterified via OH to PO4
FA1- saturated (palpitate or stearate)
FA2- unsaturated (arachidonic acid)

Question 3

where is the site of glycerophospholipid synthesis? how distributed in cell?

Answer 3

cytosolic face of ER, following synthesis will travel to golgi for distribution

Question 4

what is the simplest glycerophospholipid?

Answer 4

phosphatidic acid (head group = H)

Question 5

what results when FA1 or FA2 are removed from a glycerophospholipid?

Answer 5

lysophosphoglyceride

Question 6

what are the functions of lysophosphoglyceride in the cell?

Answer 6

signaling or pro-inflammatory

Question 7

what are the sources of glycerol-3-p?

Answer 7

• from DHAP (liver and adipose)

- free glycerol phosphorylated by glycerol kinase (liver only)

Question 8

in the synthesis of phosphatidic acid, what is the required activator of the polar head group and hydrophobic tail?

Answer 8

CTP (cytidylyl triphosphate)

Question 9

phosphatidic acid is the precursor for the synthesis of what 2 things?

Answer 9

• glycerophospholipids

- triglycerides

Question 10

what is the only antigenic human phospholipid?

Answer 10

cardiolipin

Question 11

what is the structure of cardiolipin?

Answer 11

2 molecules of esterified phosphatidic acid

Question 12

where is cardiolipin found?

Answer 12

inner mito membrane

bacterial membranes

Question 13

what is the physiologic role of cardolipin in the mitochondria?

Answer 13

cardiolipin contains an ionized “bridge” that acts as a buffer to trap H+ in the inner mito membrane and maintain electron flux in the ETC

Question 14

what is the action of cardiolipin oxygenate? consequences?

Answer 14

cardiolipin oxygenase causes per oxidation of unsaturated acyl chains on cardiolipin, triggers apoptosis

Question 15

describe apoptosis caused by cardiolipin peroxidation

Answer 15

when cardiolipin in peroxidized, a large pore forms in the inner mito membrane that allows for the passage of cytochome C into the cytosol, while in the cytosol, cytochome C binds IP3 to trigger Ca release from SER that induces more cytochrome c movement into cytosol

Question 16

2 types of ether phospholipids

Answer 16

• alkyl (saturated)

- alkenyl (unsaturated)

Question 17

2 biologically important alkenyl ether phospholipids

Answer 17

• ethanolamine plasmogen (in myelin)

- choline plasmogen (in heart mm)

Question 18

main phospholipid component of PAF?

Answer 18

phosphatidylcholine

Question 19

2 reactions mediated by PAF

Answer 19

1- acute inflammation

2- anaphylactic shock

Question 20

what cells are acted on by PAF to produce inflammation/anaphylaxis?

Answer 20

• neutrophils/macrophages = superoxide anions

- platelets = aggregation and degranulation

Question 21

how does PAF affect the cell membrane?

Answer 21

will bind to external PAF receptor, activate transmembrane signaling domain that will trigger phospholipases = phospholipid degradation

Question 22

main phospholipid component of surfactant

Answer 22

dipalmitoylphosphatidylcholine

Question 23

cells that produce surfactant

Answer 23

type II granular pneumocytes

Question 24

purposes of surfactant (3)

Answer 24

• decrease alveolar surface tension
• prevent alveolar collapse
• reduce susceptibility for free radial oxidation

Question 25

RDS/hyaline membrane disease

Answer 25

in premature infants due to inadequate lung maturity at birth, assess risk with phos-choline:sphingomyelin ratio

Question 26

respiratory failure related to surfactant

Answer 26

in adults, caused by damage to type II pneumocytes, commonly asdic with immunosuppressive medication or chemotherapy

Question 27

how is phosphatidylserine synthesized?

Answer 27

from phosphatidylethanolamine: serine is exchanged for free serine

Question 28

how is phosphatidylcholine synthesized from phosphatidylserine in the membrane?

Answer 28

- Phos-serine is decarboxylated to phos-ethanolamine - PE undergoes 3 successive methylations (donor = SAM) - Phos-choline formed

Question 29

after SAM donates methyl group, what is formed?

Answer 29

SAH (s-adenosylhomocysteine)

Question 30

what is SAM?

Answer 30

s-adenosylmethionine

Question 31

what limits the ability to perform de novo synthesis of phos-choline?

Answer 31

availability of methionine | essential aa, often deficient in diet

Question 32

besides de novo synthesis, what is another way that cells can make phis-choline?

Answer 32

using the salvage pathway (CDP-choline pathway) that will activate free choline for reincorporation into lipid membranes

Question 33

choline sources (3)

Answer 33

- synthesis in the liver - dietary intake (meats, eggs, some veggies) - recycling (Phos-choline, sphingomyelin, ACH)- using salvage pathway

Question 34

what can result from deficiency of choline?

Answer 34

impairment of brain development and memory

Question 35

general type of enzyme that degrades glycerophospholipids

Answer 35

phospholipases

Question 36

phospholipase A1

Answer 36

removes FA from sn1 position

Question 37

phospholipase A2

Answer 37

removes FA from sn2 position to yield free FA + lysophospholipid; release arachidonic acid that is used for eicosanoid synthesis and removes damaged PUFA from membrane

Question 38

phospholipase C

Answer 38

cleaves phosphodiester bond between C3 and phosphate

Question 39

phospholipase D

Answer 39

cleaves phosphodiester bond between phosphate and polar head group

Question 40

4 types of phospholipase A2

Answer 40

1- cytosolic 2- Ca-independent intracellular 3- secretory 4- pancreatin

Question 41

cytosolic phospholipase A2

Answer 41

activated by increased Ca and by phosphorylation by MAP kinase, will release arachidonic acid for eicosanoid synthesis

Question 42

calcium independent intracellular A2

Answer 42

involved in turnover and remodeling of phospholipids

Question 43

secretory A2

Answer 43

active extracellularly, role in sepsis and inflammation

Question 44

pancreatic A2

Answer 44

digestive enzyme, released as zymogen

Question 45

3 components of sphingolipids

Answer 45

- backbone= sphingosine - one fatty acid- usually saturated - polar head group

Question 46

what is the polar head group in sphingomyelin?

Answer 46

choline

Question 47

ABO group determinants are:

Answer 47

sphingolipids (specifically glycolipids)

Question 48

what is ceramide?

Answer 48

a sphingolipids that is a 2nd messenger and is important for cell differentiation or apoptosis

Question 49

what is the result of interaction between cholesterol and sphingomyelin in the cell membrane?

Answer 49

assoc with cholesterol promotes the transition from gel phase to liquid state

Question 50

what are the membrane domains assoc with sphingolipids?

Answer 50

caveolae and lipid rafts

Question 51

what enzyme will degrade sphingolipids?

Answer 51

sphingomyelinase

Question 52

what disease has a deficiency of sphingomyelinase?

Answer 52

Niemann-Pick type 1

Question 53

what are the sx of niemann-pick type 1?

Answer 53

enlarged liver and spleen due to accumulation of lipids, mental retardation, death in childhood

Question 54

what are glycolipids?

Answer 54

sphingolipids with sugar as the polar head group

Question 55

2 types of glycolipids

Answer 55

- cerebroside- ceramide + one sugar | - ganglioside- ceramide + branched sugar