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SMP - MNE Exam 1 > Lecture 19/20: Classes of Cellular Lipids and Glycerophospholipid/Sphingolipid Synthesis > Flashcards

Lecture 19/20: Classes of Cellular Lipids and Glycerophospholipid/Sphingolipid Synthesis Flashcards

1
Q

What are the 2 mechanisms to synthesize glycerophospholipids from phosphatidic acid?

A
  1. Activated diacylglycerol

2. Activated head groups

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2
Q

What is CDP?

A

Cytidine diphosphate

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3
Q

Describe the synthesis of glycerophospholipids using an activated diacylglycerol.

A
  1. Activate the DAG with CDP

2. Head group then attacks the CDP-DAG

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4
Q

Describe the synthesis of glycerophospholipids using an activated head group.

A
  1. Activate the head group with CDP

2. DAG then attacks the CDP-head group

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5
Q

What mechanism do bacteria, fungi, and mammals use to synthesize cardiolipin? Describe the 4 steps.

A

CTP activated DAG:

  1. Phosphatidic acid + CTP = CDP-DAG + PPi
  2. Add glycerol-3-phosphate + dephosphate: phosphatidylglycerol = PG
  3. PG + PG = cardiolipin
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6
Q

What mechanism do bacteria and fungi use to synthesize phosphatidylserine? Describe the 2 steps.

A

CTP activated DAG:

  1. Phosphatidic acid + CTP = CDP-DAG + PPi
  2. CDP-DAG + serine = phosphatidylserine + CMP
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7
Q

What mechanism do bacteria and fungi use to synthesize phosphatidylethanolamine? Describe the 2 steps.

A

CTP activated DAG:

  1. Make phosphatidylserine
  2. PS decarboxylase = CO2 + phosphatidylethanolamine
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8
Q

What mechanism do bacteria, fungi, and mammals use to synthesize PG? Describe the 3 steps.

A

CTP activated DAG:

  1. Phosphatidic acid + CTP = CDP-DAG + PPi
  2. Add glycerol-3-phosphate + dephosphate: phosphatidylglycerol = PG
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9
Q

What mechanism do fungi and mammals use to synthesize phosphatidylinositol? Describe the 4 steps.

A

CTP activated DAG:

  1. Make PG
  2. PG + inositol-4,5-BP = phosphatidylinositol-4,5-BP
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10
Q

What mechanism do fungi use to synthesize phosphatidylcholine? Describe the 2 steps. What other mammal organ can do this?

A

CTP activated DAG:
1. Make phosphatidylethalonamine
2. Methylate it
LIVER!

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11
Q

What mechanism do mammals use to synthesize phosphatidylcholine? Describe the 1 step.

A

Head group activation:

CDP-choline + DAG = phosphatidylcholine

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12
Q

What mechanism do mammals use to synthesize phosphatidylethanolamine? Describe the 1 step.

A

Head group activation:

CDP-ethanolamine + DAG = phosphatidylethanolamine

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13
Q

What mechanism do mammals use to synthesize phosphatidylserine? Describe the 1 step

A

Head-group exchange mechanism:

CDP-serine + PE OR PC = phosphatidylserine

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14
Q

What is the role of surfactant?

A

Reduce surface tension in the alveoli during respiration to allow the alveoli to expand

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15
Q

What are the 2 major components of surfactant?

A

2 glycerophospholipids:

  1. Dipalmitoylphosphatidylcholine (DPPC)
  2. Unsaturated phosphatidylcholine
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16
Q

When does the fetus produce surfactant?

A

35 weeks

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17
Q

What is respiratory distress syndrome? Treatment?

A

Syndrome due to lack of surfactant in premature babies

Treatment: artificial lung surfactant and O2

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18
Q

What can be measured to understand the maturity of the surfactant being produced by a premature baby? Describe the interpretation of the results.

A

Measure L/S ratio = L-phosphatidylcholine/S-sphingomyelin ratio:

  • Normal term pregnancy: >=2
  • 1.5-2: 40% chance of developing respiratory distress syndrome
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19
Q

What are 2 ether-linked glycerophospholipids? What is the difference with normal glycerophospholipids?

A
  1. Plasmalogens
  2. Platelet-activating factor
    They have an ether-linked alkane/alkene chain instead of an FA at position 1
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20
Q

What are the 2 possible head groups for plasmalogens?

A
  1. Choline

2. Ethanolamine

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21
Q

What are plasmalogens important for? 3 things

A
  1. Cardiac muscle tissues
  2. Myelin sheath
  3. Biomarker for metastatic cancers
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22
Q

Where is the double in plasmalogens? What do we call these molecules?

A

Between C1 and C2 of the alkene chain

Vynil ethers

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23
Q

Describe the composition of the platelet-activating factor. What does the position 2 portion of it allows it do to?

A
  1. Ether linked alkane chain at position 1
  2. Acetyl ester at position 2: small group allowing the molecule to circulate and be soluble in blood
  3. Phosphocholine head group at position 3
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24
Q

What are the 2 roles of platelet activating factor?

A
  1. Promotes aggregation of platelets
  2. Promotes serotonin release from platelets for vasoconstriction
  3. Important for inflammation and allergic responses
25
How is platelet-activating factor deactivated?
By removing the acetyl ester at the C2 position
26
Which one sphingolipid a phospholipid?
Sphingomyelin (with phosphocholine as a head group)
27
Describe the 3 steps of sphingolipid synthesis.
1. Sphingamine synthesis 2. Sphingamine + FA-CoA = N-acyl sphinganine (FA added to the amine group of the serine on C2) 3. Mixed-function oxidase: double bond introduced between C4 and C5 = ceramide
28
Describe the 2 steps of sphingamine synthesis. Describe sphingamine.
1. Palmitoyl-CoA + serine = β-ketosphingamine | 2. β-ketosphingamine + NADPH = sphingamine (C=O reduced to C-OH): 18 C amino alcohol
29
What is the precursor to all of the sphingolipids?
Ceramide
30
Where does ceramide synthesis take place?
SER
31
Where does the synthesis of all sphingolipids from ceramide take place?
Golgi
32
Describe the 1 step of cerebroside synthesis.
Head group activated: | Ceramide + UDP-glucose = glucocerebroside
33
What are cerebrosides?
Sphingolipid with sugar head group
34
Describe the 1 step of sphingomyelin synthesis. What is important to note?
Head group exchange: | Ceramide + phosphatidylcholine = sphingomyelin (entire phosphatidylcholine is transferred)
35
What is the precursor of globosides and gangliosides?
Glucocerebroside
36
What is the precursor of sulfatides?
Galactocerebroside
37
Describe the 1 step of sulfatide synthesis.
Galactocerebroside + PAPS (3'-phosphoadenosine-5'-phosphosulfate) = sulfatide (with sulfate group on 3-OH of galactose)
38
Where are sulfatides found in the body?
Compose 15% of brain white matter
39
Describe the 3 steps of globoside synthesis.
1. Glucocerebroside + UPD-galactose = lactosyl ceramide 2. lactosyl ceramide + UDP-sugar = trihexosyl ceramide 3. tryhexosyl ceramine + UDP-sugar = globoside
40
Describe the 3 steps of ganglioside synthesis.
1. Glucocerebroside + UPD-galactose = lactosyl ceramide 2. Lactosyl ceramide + sialic acid-CMP = ganglioside 3. Add sugars in different branches
41
What is the nomenclature for naming gangliosides?
1. G 2. # of sialic acids (M=1, D=2, T=3, Q=4) 3. 5 - # of sugar moieties
42
What are 2 major roles of glycosphingolipids?
1. Blood groups | 2. GM1: receptor for cholera toxin in human intestine
43
What does the inability to synthesize glycosphingolipids lead to?
Nonviability so no patients are born with this problem
44
Where does sphingolipid degradation occur? With what?
Lysosomes with hydrolases
45
What is the cause of glycolipid storage diseases? Treatment?
Mutations causing the defect of one of the lysosomic hydrolases responsible for breaking down sphingolipids Not much can be done as sphingolipids are present in all tissues
46
What is Tay-Sachs disease caused by? Accumulation of which sphingolipid? What does this form?
Deficient hexosaminidase A | GM2 accumulation in the lysosome forming an onion like structure that is multilaminar (composed of many bilayers)
47
What is Gaucher's disease caused by? Accumulation of which sphingolipid?
Deficient glucocerebrosidase | Glucocerebroside accumulation
48
Which glycolipid storage has 2 treatments? What are they?
Gaucher's disease: 1. Enzyme replacement therapy but very expensive 2. Substrate management
49
What are the 5 symptoms of glycolipid storage diseases?
1. Hepatosplenomegaly 2. Scoliosis 3. Corneal opacity 4. Macular spots on the retina 5. Neuromuscular issues: ataxia, dystonia, hypotonia, macroglossia
50
What 2 methods are used to screen for glycolipid storage diseases?
1. Genetic screening | 2. Enzymatic screening
51
What does the ether linkage of plasmalogen and platelet-activating factor protect them against?
1. ROS | 2. Enzyme degradation
52
Where are glycerophospholipids synthesized?
SER
53
What are the 7 steps of plasmalogen synthesis?
1. Add 1 FA to DHAP 2. Displacement of C1 FA by a long chain alcohol 3. Reduction of C2 ketone 4. Acylation of C2-OH 5. Hydrolysis of 3'-phosphate 6. Condensation with activated CDP-ethanolamine or CDP-choline 7. Double-bond introduction with NADH
54
How many Cs in the FAs of sphingomyelin?
16 and 18
55
What is the most common cerebroside?
Galactocerebroside
56
What is the usual charge of cerebrosides and globosides?
Neutral
57
What is the usual charge of sulfatides?
Negative
58
How are glycosphingolipids synthesized and degraded?
1 sugar at a time!
59
What population is at risk for Tay-Sachs disease?
Ashkenzi Jewish population (1:25 carrier frequency)

SMP - MNE Exam 1 (25 decks)

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