Phospholipid, Glycosphingolipid, Eicosanoid Metabolism Flashcards

1
Q

Why are phospholipids predominant lipids of membranes?

A

Amphipathic nature

  • Hydrophilic head extending outwards
  • Hydrophobic tails containing FAs point inside
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2
Q

What is a function of phospholipid?

A

Reservoir for intracellular messengers and protein anchors

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3
Q

What are the 2 classes of backbones for phospholipids?

A

1) Glycerol (from glucose)

2) Sphingosine (from serine + palmitate)

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4
Q

What are glycerophospholipids?

A

Glycerol + Phosphatidic acid (DAG + P)

  • Phosphate head at position #3 -> type of phospholipid
  • Predominant in membranes
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5
Q

What is the structure of cardiolipin?

A

2 molecules of PA esterified through their phosphate groups to an additional molecule of glycerol

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6
Q

What are characteristics of cardiolipin?

A

1) Virtually exclusive to inner mito. membrane

2) Maintains structure and function of certain respiratory complexes of ETC

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7
Q

What is the structure of plasmalogen?

A

Unsaturated alkyl group attached by an ETHER (rather than an ester) linkage
-“Al” vs “yl” in name

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8
Q

What function do plasmalogens have?

A

Important in nerve and heart

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9
Q

What is the structure of platelet-activating factor (PAF)?

A

Ether glycerophospholipid bond

-Funkiness: Acetyl residue at C2 (instead of FA)

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10
Q

What functions do PAF have?

A
  • Mediates hypersensitivity
  • Acute inflammatory
  • Anaphylactic rxns
  • Platelets to aggregate
  • Activate neutrophils and macrophages
  • Lower BP
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11
Q

What is the structure of sphingophospholipid?

A

Backbone = amino alcohol Sphingosine (made from palmitate + serine)

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12
Q

What is a LC FA attached to amino group sphingosine?

A

Ceramide

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13
Q

What is sphingomyelin?

A

C1 esterified to phosphorylcholine

-Only significant sphingophospholipid in humans

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14
Q

What is the function of sphingophospholipid?

A

Myelin sheath of nerve fibers

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15
Q

What is the role of phosphatidylcholine in lung surfactant?

A

Dipalmitoylphosphatidylcholine (DPPC) is a major lipid component of lung surfactant (ECF layer lining alveoli)
-Decreases surface tension, reducing pressure needed to reinflate alveoli -> prevents alveolar collapse

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16
Q

What is the structure of phosphatidylcholine?

A

Glycerol backbone + FAs at positions 1 and 2 + Choline at position 3

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17
Q

What is respiratory distress syndrome (RDS) caused by?

A
Insufficient phosphatidylcholine (surfactant production)
-In preterm infants
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18
Q

How is the lung maturity of fetus measured?

A

Ratio of DPPC : Sphingomyelin

-Value of 2+ -> maturity

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19
Q

What is the structure of phosphatidylinositol?

A

A larger molecule with arachidonic acid on C2 (for prostaglandin synthesis)

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20
Q

Where is phosphatidylinositol found primarily?

A

Inner leaflet

21
Q

What major role does phosphatidylinositol have?

A

Signal transduction

-Phosphorylation -> PIP2 -> cleaved by Phospholipase C (before phosphate) -> IP3 + DAG (2nd messengers)

22
Q

Where does phospholipase A1 cleave?

A

Cuts 1st carbon

23
Q

Where does phospholipase A2 cleave?

A

Cuts 2nd carbon

24
Q

Where does phospholipase C cleave?

A

Cuts before phosphate -> IP3 + DAG

25
Where does phospholipase D cleave?
Cuts after phosphate -> phosphatidic acid (PA)
26
What is sphingomyelinase?
Lysosomal enzyme that degrades sphingomyelin -> leaves a ceramide -> cleaved by ceramidase -> FA
27
What is Niemann-Pick disease?
Sphingomyelinase deficiency -> enlarged liver and spleen filled with lipid - Severe intellectual disability and neurodegeneration (type A) -> death in early childhood - 1/40,000 Ashkenazi jews - 1/250,000 normal pop
28
What do glycolipids contain?
Carbohydrates + lipids
29
What is the major backbone for glycosphingolipids?
Ceramide (LC FA + sphingosine)
30
What is the major difference between glycosphingolipids and sphingomyelin?
Does NOT have a phosphate, polar head is a sugar instead (a mono- or oligosaccharide in O- glycosidic bond)
31
Where are glycolipids found?
In all membranes (in outer leaflet) - Greatest amount in nerve tissue - Will be neutral in brain
32
What are 5 roles of glycolipids?
1) Regulation of cellular interactions 2) Growth 3) Development 4) Blood group antigens 5) Receptors for cholera, tetanus toxins and some viruses
33
What are 3 of the most known eicosanoids?
1) Prostaglandins 2) Thromboxanes 3) Leukotrienes
34
What are eicosanoids known for?
Extremely potent compounds, elicit wide range of responses, both physiologic (inflammatory response) and pathologic (hypersensitivity)
35
What functions are mediated by eicosanoids?
- Ensure gastric integrity - Renal function - Regulate smooth muscle contraction - Blood vessel diameter - Maintain platelet homeostasis
36
What cells are able to produce eicosanoids?
All tissues produce them in very small amounts
37
Do eicosanoids act locally or are they transported in blood to distant sites?
Act locally
38
What is the half-life of eicosanoids?
Extremely short half-life -> rapidly metabolized to inactive products -Are not stored
39
How do eicosanoids work?
Through G protein-coupled receptors
40
What is the most common precursor for eicosanoids?
Arachidonic acid (omega-6, 20-C, 4 double bonds) - We cannot make omega-6 so we need a dietary essential FA (linoleic acid; 18 C) to make arachidonic acid - Eicosatetraenoic FA (eicosa = 20, tetra = 4 double bonds)
41
What is arachidonic acid released by?
Arachidonic acid is stored in our cells as part of the plasma membrane in the 2nd position of glycerol -> Phospholipase A2 (chops at 2nd C) when we need arachidonic acid
42
What 2 enzymes are required for synthesis of prostaglandins and thromboxanes?
1) COX (makes ring and requires O2) | 2) Peroxidase (dependent on reduced glutathione)
43
What are 2 isozymes of PGH synthase?
1) COX-1 (normal) | 2) COX-2 (inducible -> inflammation and immune response)
44
What does COX-1 do?
Maintain healthy gastric tissue, renal homeostasis and platelet aggregation
45
What does COX-2 do?
Respond to products of activated immune and inflammatory cells -Mediates pain, heat, redness and swelling of inflammation and fever of infection
46
What does cortisol (steroidal anti-inflammatory) inhibit?
Phospholipase A2 | -Shuts it down earlier, you don't even get arachidonic acid
47
What does aspirin and NSAIDs inhibit?
COX-1 and COX-2
48
What is aspirin toxicity?
Systemic COX-1 inhibition -> damage to stomach, kidneys and impaired clotting of blood
49
What does celebrex inhibit?
Only COX-2