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
Q

Where does phospholipase D cleave?

A

Cuts after phosphate -> phosphatidic acid (PA)

26
Q

What is sphingomyelinase?

A

Lysosomal enzyme that degrades sphingomyelin -> leaves a ceramide -> cleaved by ceramidase -> FA

27
Q

What is Niemann-Pick disease?

A

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
Q

What do glycolipids contain?

A

Carbohydrates + lipids

29
Q

What is the major backbone for glycosphingolipids?

A

Ceramide (LC FA + sphingosine)

30
Q

What is the major difference between glycosphingolipids and sphingomyelin?

A

Does NOT have a phosphate, polar head is a sugar instead (a mono- or oligosaccharide in O- glycosidic bond)

31
Q

Where are glycolipids found?

A

In all membranes (in outer leaflet)

  • Greatest amount in nerve tissue
  • Will be neutral in brain
32
Q

What are 5 roles of glycolipids?

A

1) Regulation of cellular interactions
2) Growth
3) Development
4) Blood group antigens
5) Receptors for cholera, tetanus toxins and some viruses

33
Q

What are 3 of the most known eicosanoids?

A

1) Prostaglandins
2) Thromboxanes
3) Leukotrienes

34
Q

What are eicosanoids known for?

A

Extremely potent compounds, elicit wide range of responses, both physiologic (inflammatory response) and pathologic (hypersensitivity)

35
Q

What functions are mediated by eicosanoids?

A
  • Ensure gastric integrity
  • Renal function
  • Regulate smooth muscle contraction
  • Blood vessel diameter
  • Maintain platelet homeostasis
36
Q

What cells are able to produce eicosanoids?

A

All tissues produce them in very small amounts

37
Q

Do eicosanoids act locally or are they transported in blood to distant sites?

A

Act locally

38
Q

What is the half-life of eicosanoids?

A

Extremely short half-life -> rapidly metabolized to inactive products
-Are not stored

39
Q

How do eicosanoids work?

A

Through G protein-coupled receptors

40
Q

What is the most common precursor for eicosanoids?

A

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
Q

What is arachidonic acid released by?

A

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
Q

What 2 enzymes are required for synthesis of prostaglandins and thromboxanes?

A

1) COX (makes ring and requires O2)

2) Peroxidase (dependent on reduced glutathione)

43
Q

What are 2 isozymes of PGH synthase?

A

1) COX-1 (normal)

2) COX-2 (inducible -> inflammation and immune response)

44
Q

What does COX-1 do?

A

Maintain healthy gastric tissue, renal homeostasis and platelet aggregation

45
Q

What does COX-2 do?

A

Respond to products of activated immune and inflammatory cells
-Mediates pain, heat, redness and swelling of inflammation and fever of infection

46
Q

What does cortisol (steroidal anti-inflammatory) inhibit?

A

Phospholipase A2

-Shuts it down earlier, you don’t even get arachidonic acid

47
Q

What does aspirin and NSAIDs inhibit?

A

COX-1 and COX-2

48
Q

What is aspirin toxicity?

A

Systemic COX-1 inhibition -> damage to stomach, kidneys and impaired clotting of blood

49
Q

What does celebrex inhibit?

A

Only COX-2