Membrane Lipids Flashcards

1
Q

Amphipathic

A
  • Hydrophilic head group
  • hydrophobic FA tails
  • Bilayer forms with tails pointing in and heads out interacting w/ H2O
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2
Q

Major Phospholipids w/ Function

A
  1. Phosphatydic Acid: major constituents of cell membranes
  2. Phosphatidylethanolamine : nervous tissue such as the white matter of brain, nerves, neural tissue, and in spinal cord,
  3. Phosphatidylcholine: found in the exoplasmic or outer leaflet of a cell membrane.
  4. Phosphatidylserine: inner-leaflet of cell membranes
  5. Phosphatidylinositol: Roles in lipid signaling, cell signaling and membrane trafficking
  6. Cardiolipin: Regulates aggregate structures
  7. Phosphatidylglycerol: found in pulmonary surfactant
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3
Q

Phosphatidic Acid Synthesis

A
  • Glycerol–>glycerol-3-phosphate
    * Mediated by glycerol kinase
    * uses ATP
    • G3P–>phosphatidic acid
      • acyl transferase
      • Req FA binding protein
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4
Q

Phosphatidylcholine Synthesis

A
  • CTP activates choline head group:
    • CTP+choline–>CDP-choline
    • cytidyl transferase
  • Phosphatidic acid–>diacylglycerol (DAG)
    • Phosphatidic acid phosphatase (P cleaved)
  • DAG+CDP-choline–>phosphatidylcholine
  • Also formed from PE:
    • phosphatidylethanolamine methyltransferase (PEMT)
    • Converts PE to PC by sequential methylation in liver
    • Req S adenocyl methionine
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5
Q

Phosphatidylethanolamine Synthesis

A
  • CTP activates ethanolamine head group:
    • CTP+ethanolamine–>CDP-ethanolamine
    • cytidyl transferase
  • Phosphatidic acid–>diacylglycerol (DAG)
    • Phosphatidic acid phosphatase (P cleaved)
  • DAG+CDP-ethanolamine–> phosphatidylethanolamine
  • Also produced by conversion from Phosphatidylserine
    • PS decarboylase
    • Releases CO2
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6
Q

Phosphatidylserine Synthesis

A
  • CTP activates serine head group:
    • CTP+serine–>CDP-serine
    • cytidyl transferase
  • Phosphatidic acid–>diacylglycerol (DAG)
    • Phosphatidic acid phosphatase (P cleaved)
  • DAG+CDP-serine–> phosphatidylserine
  • Also produced by conversion from PE:
    • PS synthase converts the 2 head groups
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7
Q

Phosphatidylinositol Synthesis

A
  • Phosphatidic acid activated by CTP
    • PA+CTP–>CDP-DAG
    • transferase
    • Releases PPi
  • Inositol head group added
    • CMP released
    • PI synthase
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8
Q

Cardiolipin Synthesis

A
  • Phosphatidic acid activated by CTP
    • PA+CTP–>CDP-DAG
    • transferase
    • Releases PPi
  • PG head group added
    • nucleophilic attack by PG on PA
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9
Q

Phophatidylglycerol Synthesis

A
  • Phosphatidic acid activated by CTP
    • PA+CTP–>CDP-DAG
    • transferase
    • Releases PPi
  • glycerol head group added
    • CMP released
    • PG synthase
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10
Q

Location of Membrane lipid synthesis

A

-Cytosolic face of ER
_Except for plasmalogens (ether glycerlipids) they are synthesized in peroxisome
-

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11
Q

6 fumctions of Phospholipids

A
  1. Converted to arachidonic acid
  2. Lung surfactant
  3. Blood lipoproteins
  4. Membranes
  5. Bile
  6. Platelet activation
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12
Q

Major components of Membranes

A
  • Fxn to sperate cytosol from extacellular space
    • Outer leaflet: PC, sphingomyelin
    • Inner leaflet: PE, PS, PI
  • intracellular compartmentalization
  • Affects fluidity
    • Saturated FA are very tight and rigid
    • Unsaturated FA increase fluidity
    • Cholesterol increases fluidity by interfering w. lipid packing
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13
Q

Precursors to signaling Molecules

A
  • Arachidonic Acid: Eicosanoids
  • PA: activate kinases
  • Sphingosine: angiogenesis
  • Isoprostanes: From free radical peroxidation of AA
    • inflammatory mediators
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14
Q

Emulsifiers

A

-Phospholipids promote bile function
-dispersion of tiacylglycerols and cholesterol esters
Solubilize cholesterol in bile
-Critical components of lipoproteins
*Transport cholesterol in circulation

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15
Q

Lung Surfactant

A
  • Type II alveolar cells produce surfactant

- Reduces surface tension and lowers pressure required to inflate alveoli

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16
Q

Ether glycerolipids (2)

A
  1. Plamologens

2. Platelet activating factor

17
Q

Sphingophospholipids (1)

A
  1. Sphingomyelin
18
Q

Glycolipids (4)

A
  1. Cerebrosides
  2. Sulfatides
  3. Globosides
  4. Gangliosides
19
Q

Plasmalogen Syntheseis

A
  1. DHAP+FA-CoA–>1-acyl-DHAP
    -DHAP acyltransferase
    2.Replace FA w/ROH forming ether linkage
    _Alkyl DHAP synthase
  2. Reduces C2 ketone to alcohol
  3. Add fatty acid to the alcohol
  4. Dephosphorylation
  5. Reacts w/ activated head groups
    -CDP-ethalamine or CDP-choline
    7.Desaturation of FA using NADPH and O2
    -forms final plasmalogen
20
Q

Functions of Plasmalogens (3)

A
  1. Ethanolamine plasmalogen found in myelin
  2. Choline plasmalogen in heart muscle
  3. Platelet activating factor fxn in platelet aggregation and inflammation
    • formed from remodeling
21
Q

Platelet Activating Factor

A
  • Synthesized in response to stimulation
    • Glycerphosphocholin releases FA
    • Forms Lyso-PAF:
    • Acetyltransferase forms final PAF
  • Function: kinase activation
    • inflammation modulation
22
Q

Shingolipids

A
  • backbone from serine
  • FA and head group
  • Ceramide: Backbone+FA amide
23
Q

Ceramide Synthesis

A
  1. Serine+palmitoyl CoA
    • Serine decarboylated & displaces CoA
  2. Reduction of ketone to alcohol
    • Uses NADPH
    • forms dihydroshingosine
  3. Addition of FA group
    • forms N-FA derivative
  4. Oxidation of FA using FAD
    - Forms ceramide
24
Q

Sphingomyelin Synthesis

A
  • Ceramide+PC–>Sphengomyelin
    • DAG released
  • Insulates and protects nerve axons
  • Ensures rapid signal transmission
25
Q

Sulfatide Synthesis

A
  1. Ceramide+UDP-galactose–> galactocerbroside
  2. Sulfate transferase adds sulfate group to glactose
    - Major brain sulfolipid
26
Q

Globoside Synthesis

A
  1. Ceramide+UDP-Glucose–> glucocerebroside

2. Galactose added by UDP-Gal

27
Q

Ganglioside Synthesis

A
  1. Ceramide+UDP-Glucose–> glucocerebroside
  2. Addition of UDP-sugars
  3. CMP-NANA added to Gal
    - Negatively charged ceramide oligosaccharides
28
Q

Phospholipases

A

PLA1: hydrolyzes ester at position 1
PLA2: releases FA w/ ester hydrolysis @ FA2
PLC: Hydrolyzes phosphate forming DAG
PLC: hydrolyzes phosphate forming PA

29
Q

Sphingolipids in V. Cholerae

A
  • toxin effects mediated by interaction w/ GM1 gangliosides on intestinal mucosa cells
  • toxin ribosylate G-alpha and increases cAMP causing water loss and diarrhea
30
Q

Flu Transmission

A
  • Viral nuraminidase cleaves NANA from cell receptor
  • allows release of virus particles
  • Nuraminidase inhibitors halt spread of infection
31
Q

Niemann Pick

A
  • accumulation of sphingomyelin in brain & blood cells
  • sphingomyelinase deficiency
  • MR, spasticity, seizures, ataxia, death by age 2-3
  • Autosomal Recessive
32
Q

Fabry Disease

A
  • accumulation of glycolipids in brain, heart, kidney
  • alpha galactosidase A deficiency
  • pain in extremities, skin lesions, ischemic infarction of kidney, brain, heart
33
Q

Krabbe disease

A

-accumulation of glycolipids destroying oligodendrocytes
-beta galactosidase deficiency
-demyelination: spasiticty & neurodegeneration leading to death
Hypotonia, hyperreflexia, blind, deaf

34
Q

Gaucher disease

A
  • accumulation of glucocerebrosides in blood, liver, spleen
  • glucocerebrosidase deficiency
  • hepatosplenomegaly, anemia, thrombocytopenia, bone pain, femur deformity
35
Q

Tay-Sachs disease

A
  • accumulation of GM2 gangliosides in neurons
  • Hexosaminidase A deficiency
  • Progressive neurodegeneration, developmental delay, death