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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
Q

How is platelet-activating factor deactivated?

A

By removing the acetyl ester at the C2 position

26
Q

Which one sphingolipid a phospholipid?

A

Sphingomyelin (with phosphocholine as a head group)

27
Q

Describe the 3 steps of sphingolipid synthesis.

A
  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
Q

Describe the 2 steps of sphingamine synthesis. Describe sphingamine.

A
  1. Palmitoyl-CoA + serine = β-ketosphingamine

2. β-ketosphingamine + NADPH = sphingamine (C=O reduced to C-OH): 18 C amino alcohol

29
Q

What is the precursor to all of the sphingolipids?

A

Ceramide

30
Q

Where does ceramide synthesis take place?

A

SER

31
Q

Where does the synthesis of all sphingolipids from ceramide take place?

A

Golgi

32
Q

Describe the 1 step of cerebroside synthesis.

A

Head group activated:

Ceramide + UDP-glucose = glucocerebroside

33
Q

What are cerebrosides?

A

Sphingolipid with sugar head group

34
Q

Describe the 1 step of sphingomyelin synthesis. What is important to note?

A

Head group exchange:

Ceramide + phosphatidylcholine = sphingomyelin (entire phosphatidylcholine is transferred)

35
Q

What is the precursor of globosides and gangliosides?

A

Glucocerebroside

36
Q

What is the precursor of sulfatides?

A

Galactocerebroside

37
Q

Describe the 1 step of sulfatide synthesis.

A

Galactocerebroside + PAPS (3’-phosphoadenosine-5’-phosphosulfate) = sulfatide (with sulfate group on 3-OH of galactose)

38
Q

Where are sulfatides found in the body?

A

Compose 15% of brain white matter

39
Q

Describe the 3 steps of globoside synthesis.

A
  1. Glucocerebroside + UPD-galactose = lactosyl ceramide
  2. lactosyl ceramide + UDP-sugar = trihexosyl ceramide
  3. tryhexosyl ceramine + UDP-sugar = globoside
40
Q

Describe the 3 steps of ganglioside synthesis.

A
  1. Glucocerebroside + UPD-galactose = lactosyl ceramide
  2. Lactosyl ceramide + sialic acid-CMP = ganglioside
  3. Add sugars in different branches
41
Q

What is the nomenclature for naming gangliosides?

A
  1. G
  2. # of sialic acids (M=1, D=2, T=3, Q=4)
  3. 5 - # of sugar moieties
42
Q

What are 2 major roles of glycosphingolipids?

A
  1. Blood groups

2. GM1: receptor for cholera toxin in human intestine

43
Q

What does the inability to synthesize glycosphingolipids lead to?

A

Nonviability so no patients are born with this problem

44
Q

Where does sphingolipid degradation occur? With what?

A

Lysosomes with hydrolases

45
Q

What is the cause of glycolipid storage diseases? Treatment?

A

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
Q

What is Tay-Sachs disease caused by? Accumulation of which sphingolipid? What does this form?

A

Deficient hexosaminidase A

GM2 accumulation in the lysosome forming an onion like structure that is multilaminar (composed of many bilayers)

47
Q

What is Gaucher’s disease caused by? Accumulation of which sphingolipid?

A

Deficient glucocerebrosidase

Glucocerebroside accumulation

48
Q

Which glycolipid storage has 2 treatments? What are they?

A

Gaucher’s disease:

  1. Enzyme replacement therapy but very expensive
  2. Substrate management
49
Q

What are the 5 symptoms of glycolipid storage diseases?

A
  1. Hepatosplenomegaly
  2. Scoliosis
  3. Corneal opacity
  4. Macular spots on the retina
  5. Neuromuscular issues: ataxia, dystonia, hypotonia, macroglossia
50
Q

What 2 methods are used to screen for glycolipid storage diseases?

A
  1. Genetic screening

2. Enzymatic screening

51
Q

What does the ether linkage of plasmalogen and platelet-activating factor protect them against?

A
  1. ROS

2. Enzyme degradation

52
Q

Where are glycerophospholipids synthesized?

A

SER

53
Q

What are the 7 steps of plasmalogen synthesis?

A
  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
Q

How many Cs in the FAs of sphingomyelin?

A

16 and 18

55
Q

What is the most common cerebroside?

A

Galactocerebroside

56
Q

What is the usual charge of cerebrosides and globosides?

A

Neutral

57
Q

What is the usual charge of sulfatides?

A

Negative

58
Q

How are glycosphingolipids synthesized and degraded?

A

1 sugar at a time!

59
Q

What population is at risk for Tay-Sachs disease?

A

Ashkenzi Jewish population (1:25 carrier frequency)

SMP - MNE Exam 1 (25 decks)

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