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Tissues > T17 - Glycerophospholipids and Lipid Signaling > Flashcards

T17 - Glycerophospholipids and Lipid Signaling Flashcards

1
Q

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

A

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)

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2
Q

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

A

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

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3
Q

In embryological development, when is surfactant synthesis initiated?

A

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

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4
Q
A
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5
Q

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

A

3 weeks

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6
Q

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

A

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

start to actually secrete surfactant at 30 weeks

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7
Q

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

A

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

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8
Q

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

A

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)

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9
Q

Describe the composition of surfactant.

A

80% glycerophospholipid

10% cholesterol

10% protein

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10
Q

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

A

dipalmitoylphosphatidylcholine (DPPC)

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

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11
Q

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

A

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)

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12
Q

What is the most common glycerophospholipid?

A

phosphatidylcholine

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13
Q

Describe the structure of a glycerophospholipid.

A

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

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14
Q

Describe the polarity of glycerophospholipids.

A

Glycerophospholipids are highly amphipathic

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15
Q

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

A

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

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16
Q

Describe the function of glycerophospholipids as membrane anchors for proteins.

A

phosphatidylinositol used to tether proteins/enzymes to plasma membrane

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17
Q

Describe the function of glycerophospholipids as bioactive molecules.

A

used in platelet-activating factor (PAF)

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18
Q

Describe the function of glycerophospholipids as reservoirs for prostaglandin precursors.

A

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

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19
Q

Describe the function of glycerophospholipids as reservoirs for second messengers.

A

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

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20
Q

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

A

phospholipase A

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21
Q

Describe how plasmalogens differ structurally from glycerophospholipids.

A

have an alkenyl ehter moiety in sn-1 position

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22
Q

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).

A

PAF

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23
Q

What is the precursor molecule for all glycerophospholipids?

A

phosphatidic acid

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24
Q

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

A

phosphatidylcholine

phosphatidylethanolamine

triacylglycerol

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25
Q

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

A

phosphatidylinositol

cardiolipin

phosphatidylgclyerol-phosphate

26
Q

Describe how phosphatidylserine is formed.

A

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

27
Q

What enzyme converts phosphatidic acid to diacylglycerol?

A

PAPase

28
Q

What enzyme converts phosphatidic acid to CDP-diacylglycerol?

A

CTP:phosphatidate cytidyltransferase

29
Q

Draw out the pathway of phosphatidic acid/phosphatidate formation.

A
30
Q

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

A
31
Q

What enzyme is the key regulator in glycerophospholipid synthesis?

A

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

32
Q

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

A

acyltransferase

33
Q

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

A

PC

PE

34
Q

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

A

Kennedy/base activation pathway

35
Q

Write out the pathway for phosphatidylcholine synthesis.

A

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

36
Q

Write out the pathway for phosphatidylethanolamine synthesis.

A

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

37
Q

What is the regulated step in phosphatidylcholine/ethanolamine synthesis?

A

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

38
Q

What activates CTP:phosphocholine cytidylyltransferase? (2)

A

long chain fatty acids

fatty acyl-CoAs

39
Q

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

A

base exchange reaction

40
Q

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

A

Requires the presence of Ca2+

41
Q

What is the committed step in glycerophospholipid synthesis?

A

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

42
Q

How does CDP-diacylglycerol become phosphatidylglycerol-phosphate?

A

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

43
Q

How does CDP-diacylglycerol become phosphatidylinositol?

A

CDP-diacylglycerol + myo-inositol → phosphatidylinositol

44
Q

How does CDP-diacylglycerol become cardiolipin?

A

phosphatidylglycerol + CDP-diacylglycerol → cardiolipin

45
Q

Phospholipase A2 is produced by

A

the pancreas

46
Q

What is the function of phospholipase A2?

A

digestion of dietary phospholipids

47
Q

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

A

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

48
Q

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

A

phospholipase A2 and phospholipase C

49
Q

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

A
50
Q

Describe how phosphatidylcholine is remodeled to create DPPC.

A

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

51
Q

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.

A
52
Q

What are the normal calcium levels in the cytoplasm?

A

10-6 M

53
Q

What are the normal calcium levels in the extracellular fluid?

A

10-3 M

54
Q

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

A

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

55
Q

What is the effect of activating PKC?

A

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

56
Q

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

A

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

57
Q

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

A

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

58
Q

Phospholipase A2 is activated by

A

increased Ca2+ levels

59
Q

Phospholipase C mediates what cleavage reaction?

A

PIP2 → DAG + IP3

60
Q

PIP2 → DAG + IP3 is mediated by what enzyme?

A

phospholipase C

Tissues (23 decks)

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