T17 - Glycerophospholipids and Lipid Signaling

Question 1

Describe the relationship between phospholipids, surfactant, and premature birth.

Answer 1

phospholipid-rich surfactant, which reduces surface tension, is necessary for infants to breathe

in premature infants, surfactant is not produced, meaning alveoli are collapsed and baby cannot breathe properly → neonatal respiratory distress syndrome (RDS)

Question 2

Describe what an X-ray of an infant with neonatal respiratory distress syndrome would look like.

Answer 2

would see white space that indicates alveolar collapse (normally, should be black to indicate presence of air)

Question 3

In embryological development, when is surfactant synthesis initiated?

Answer 3

initiated in fetal lungs after 75% of gestation is complete (~24 weeks)

Question 5

In embryological development, when do the lungs start to develop?

Answer 5

3 weeks

Question 6

Which cell in fetuses is responsible for storing lung surfactant? When does this cell start to actually secrete surfactant?

Answer 6

Type II cells, containing lamellar bodies, store surfactant (these cells appear at 24 weeks)

start to actually secrete surfactant at 30 weeks

Question 7

What clinical test is used to determine whether there is sufficient surfactant in a fetus?

Answer 7

lecithin:sphingomyelin (L/S) ratio — samples amniotic fluid, into which surfactant is secreted

Question 8

Describe how the lecithin:sphingomyelin (L/S) test is carried out.

Answer 8

lecithin = another name for phosphatidylcholine, the major phospholipid component of surfactant

sphingomyelin is used as a baseline (derived from fetal cells sloughed into amniotic fluid)

Question 9

Describe the composition of surfactant.

Answer 9

80% glycerophospholipid

10% cholesterol

10% protein

Question 10

What is the major/active component of surfactant? Describe its structure.

Answer 10

dipalmitoylphosphatidylcholine (DPPC)

contains two saturated fatty acids (C16:0) at sn-1 and sn-2 positions

Question 11

Why is dipalmitoylphosphatidylcholine (DPPC) in surfactant highly surface-active?

Answer 11

because DPPC molecules line up efficiently at alveolar air-liquid interface and block hydrogen bonding of H₂O with one another (i.e. reduces surface tension)

Question 12

What is the most common glycerophospholipid?

Answer 12

phosphatidylcholine

Question 13

Describe the structure of a glycerophospholipid.

Answer 13

glycerol backbone

sn-1 O esterified to saturated, long-chain FA (i.e. stearic or palmitic)

sn-2 O esterified to polyunsaturated FA (i.e. arachidonic or linoleic)

C-3 OH esterified to phosphate

Question 14

Describe the polarity of glycerophospholipids.

Answer 14

Glycerophospholipids are highly amphipathic

Question 15

Give an example of a glycerophospholipid serving as a component of plasma lipoproteins.

Answer 15

phosphatidylcholine (lecithin) — serves as the substrate for lecithin-cholesterol acyltransferase (LCAT), which forms HDL particles

Question 16

Describe the function of glycerophospholipids as membrane anchors for proteins.

Answer 16

phosphatidylinositol used to tether proteins/enzymes to plasma membrane

Question 17

Describe the function of glycerophospholipids as bioactive molecules.

Answer 17

used in platelet-activating factor (PAF)

Question 18

Describe the function of glycerophospholipids as reservoirs for prostaglandin precursors.

Answer 18

arachidonic and linoleic acids (prostaglandin precursors) are released from sn-2 position by phospholipases

Question 19

Describe the function of glycerophospholipids as reservoirs for second messengers.

Answer 19

phosphotidylinositol-containing compound (PIP₂) can be converted into the second messengers DAG and IP₃.

Question 20

What enzyme liberates arachidonic or linoleic acid from the sn-2 position of glycerophospholipids?

Answer 20

phospholipase A

Question 21

Describe how plasmalogens differ structurally from glycerophospholipids.

Answer 21

have an alkenyl ehter moiety in sn-1 position

Question 22

Give an example of a molecule that has an alkyl chain at the sn-1 position of the glycerol backbone (instead of a saturated fatty acid).

Answer 22

PAF

Question 23

What is the precursor molecule for all glycerophospholipids?

Answer 23

phosphatidic acid

Question 24

One of the two products of phosphatidic acid is diacylglycerol. Diacylglycerol can be further converted into which compounds?

Answer 24

phosphatidylcholine

phosphatidylethanolamine

triacylglycerol

Question 25

One of the two products of phosphatidic acid is CDP-diacylglycerol. CDP-diacylglycerol can be further converted into which compounds?

Answer 25

phosphatidylinositol cardiolipin phosphatidylgclyerol-phosphate

Question 26

Describe how phosphatidylserine is formed.

Answer 26

phosphatidic acid → diacylglycerol → phosphatidylcholine + phosphatidylethanolamine → [base exchange] → phosphatidylserine

Question 27

What enzyme converts phosphatidic acid to diacylglycerol?

Answer 27

PAPase

Question 28

What enzyme converts phosphatidic acid to CDP-diacylglycerol?

Answer 28

CTP:phosphatidate cytidyltransferase

Question 29

Draw out the pathway of phosphatidic acid/phosphatidate formation.

Answer 29

Question 30

Draw out a diagram that shows how phosphatidic acid is further converted to other glycerolipids.

Answer 30

Question 31

What enzyme is the key regulator in glycerophospholipid synthesis?

Answer 31

PAPase — exists in inactive cytosolic form and active membrane-associated form

Question 32

What enzyme esterifies fatty acids to the sn-1/sn-2 positions of the glycerol backbone?

Answer 32

acyltransferase

Question 33

Quantitatively speaking, which phospholipids are most important in mammalian cells? (2)

Answer 33

PC PE

Question 34

What is the major pathway to synthesize PE and PC, the two most important phospholipids?

Answer 34

Kennedy/base activation pathway

Question 35

Write out the pathway for phosphatidylcholine synthesis.

Answer 35

choline → [choline kinase, ATP] → phosphocholine → [CTP:phosphocholine cytidylyltransferase, CTP] → CDP-choline → [+ DAG, phosphotransferase] → phosphatidylcholine

Question 36

Write out the pathway for phosphatidylethanolamine synthesis.

Answer 36

ethanolamine → [ethanolamine kinase, ATP] → phosphoethanolamine → [CTP:phosphoethanolamine cytidylyltransferase, CTP] → CDP-ethanolamine → [+ DAG, phosphotransferase] → phosphatidylethanolamine

Question 37

What is the regulated step in phosphatidylcholine/ethanolamine synthesis?

Answer 37

CTP:phosphocholine cytidylyltransferase — exists in inactive monomeric cytosolic form and active tetrameric membrane-associated form [much like PAPase]

Question 38

What activates CTP:phosphocholine cytidylyltransferase? (2)

Answer 38

long chain fatty acids fatty acyl-CoAs

Question 39

Draw out a diagram illustrating phosphatidylserine synthesis. What is the name for this type of reaction?

Answer 39

base exchange reaction

Question 40

The synthesis of phosphatidylserine requires what cofactor/coenzyme/vitamin/molecule/ion?

Answer 40

Requires the presence of **Ca²⁺**

Question 41

What is the committed step in glycerophospholipid synthesis?

Answer 41

phosphatidic acid + CTP → CDP-diacylglycerol (mediated by CTP:phosphatidate cytidylyltransferase)

Question 42

How does CDP-diacylglycerol become phosphatidylglycerol-phosphate?

Answer 42

CDP-glycerol + glycerol-3-phosphate → **phosphatidylglycerol phosphate** → [can be further metabolized] → phosphatidylglycerol

Question 43

How does CDP-diacylglycerol become phosphatidylinositol?

Answer 43

CDP-diacylglycerol + myo-inositol → phosphatidylinositol

Question 44

How does CDP-diacylglycerol become cardiolipin?

Answer 44

phosphatidylglycerol + CDP-diacylglycerol → cardiolipin

Question 45

Phospholipase A2 is produced by

Answer 45

the pancreas

Question 46

What is the function of phospholipase A2?

Answer 46

digestion of dietary phospholipids

Question 47

Explain what gives rise to the deadly nature of snake venom. (4)

Answer 47

phospholipase A2 causes release of arachidonic acid from host cell membranes → metabolized to prostaglandins, causing pain + inflammation → released phospholipids are powerful detergents that digest host cell membranes → edema and hydrolysis

Question 48

What two enzymes are responsible for metabolic turnover of glycerophospholipids in mammalian cells?

Answer 48

phospholipase A2 and phospholipase C

Question 49

Draw out a diagram of a generic glycerophospholipid, and indicate where the 4 major phospholipases (A1, A2, C, D) cleave the molecule.

Answer 49

Question 50

Describe how phosphatidylcholine is remodeled to create DPPC.

Answer 50

phospholipase A2 cleaves off the unsaturated fatty acid of PC, forming lysophosphatidylcholine, which then reacts with palmitoyl-CoA to form DPPC

Question 51

Draw a diagram showing the signaling pathway that occurs when a hormone such as epinephrine binds to a GPCR. Identify molecules that inhibit parts of the pathway.

Answer 51

Question 52

What are the normal calcium levels in the cytoplasm?

Answer 52

10^-6 M

Question 53

What are the normal calcium levels in the extracellular fluid?

Answer 53

10^-3 M

Question 54

What effects can increased free calcium in the cytosol have on a cell? (4) How does calcium carry out these effects? (2)

Answer 54

changes in cell shape/motility contraction of muscle cells release of secretory proteins activation of regulatory enzymes binds to calcium-binding proteins such as _calmodulin_ in non-muscle cells and _troponin C_ in striated muscle cells

Question 55

What is the effect of activating PKC?

Answer 55

PKC activation → activation of transcription factor AP-1 → regulation of genes that promote cell proliferation

Question 56

What is the composition of the transcription factor AP-1?

Answer 56

heterodimer of c-Fos and c-Jun cellular protooncogene products

Question 57

List the steps of the pathway that begins with insulin and ends with activation of Akt. (9)

Answer 57

insulin → activate receptor tyrosine kinase → IRS proteins dock and are phosphorylated → PI3 kinases bind to phosphorylated IRS → PI3Ks then phosphorylate PIP2 → PIP3 → activation of PDK1 → phosphorylation/activation of Akt/PBK → activates GLUT4 uptake

Question 58

Phospholipase A2 is activated by

Answer 58

increased Ca²⁺ levels

Question 59

Phospholipase C mediates what cleavage reaction?

Answer 59

PIP2 → DAG + IP3

Question 60

PIP2 → DAG + IP3 is mediated by what enzyme?

Answer 60

phospholipase C