Phospholipids and Glycolipids Flashcards

1
Q

Phospholipids

A
  • Amphipaths: polar head group and non-polar FA tails
  1. Phosphoglycerides
  2. Sphingomyelins
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2
Q

Phosphoglycerides

structure

examples

A
  • glycerol backbone, two FAs, a phosphorylated head group
  • Phosphatidic acid (PA) is the simplest
    • PS
    • PC
    • PE
    • PI
    • cardiolipin
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3
Q

Sphingomyelins

structure

examples

A
  • Sphingosine backbone
  • one C of sphingosine attached to a phosphocholine
  • one C of sphingosine attached to a FA via amide linkage
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4
Q

Functions of Phospholipids

A
  • structural components of cell membrane
  • sources of arachidonic acid
  • generate second messenger molecules
  • modification of several membrane-associated proteins in their transit from the ER to the membrane
    • isoprenoid
    • Glycosylphosphatidylinositol(GPI) can serve as a membrane anchors for different proteins
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5
Q

Biosynthesis of Phospholipids

A
  • in liver, adipose tissue, and the intestine
  • generated using components from TG synthesis
    • Glycerol-3-P–>
      • DHAP—> Plasmalogens OR PAF
      • PA–>cardiolipin OR PI–>PIP2
        • DAG–>TGsORPC,PE,PS
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6
Q

Two routes for phospholipid biosynthesis

A
  1. Activate DAG backbone with CDP–>add head group–>
    • PI
    • Phosphotidylglycerol
    • cardiolipin
  2. Activate head group with CDP–>add DAG backbone–>
    • PC
    • PE
    • PS
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7
Q

CDP synthesis

A
  1. Synthesis of P-Choline

ATP + choline –(Choline kinase)–>P-Choline + ADP

  1. Activation of P-Choline

CTP + P-Choline –> CDP-choline + PPi

* CDP-ethanolamine is generated similarily

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8
Q

Biosynthesis of PE, PC, and PS from PA

A

PA–>DAG—>

  1. DAG + CDP-ethanolamine–> PE + CMP
    1. PE + 3 SAM –> PC
    2. PE + Serine –> PS + Ethanolamine
      1. PS –> PE + CO2
  2. DAG + CDP-choline–> PC + CMP
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9
Q

Biosynthesis of PI, phosphatidylglycerol and cardiolipin

A
  1. PA + CTP –> CDP-diacylglycerol + PPi
    1. CDP-diacylglycerol + inositol –> PI + CMP
      1. PI –(kinase)–>PIP–(kinase)–>PIP2
    2. CDP-diacylglycerol + glycerol –> phoshphatidylglycerol + CMP
    3. CDP-diacylglycerol + phosphatidylglycerol –> cardiolipin
  • PIP2: precursor for 2ndary messenger molecule
  • PI anchors membrane proteins
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10
Q

Respiratory Distress Syndroms (RDS)

A
  • deficiency in lung surfactant
  • surfactant: dipalmitoylphosphatidyl-choline, phosphatidylglycerol, apoproteins, and cholesterol
  • Dipalmitoylphosphatidyl-choline is synthesized by type II granular pneumocytes of the lung
  • In adults, RDS can result from the destruction of surfactant producing cells by immunosuppressive chemotherapeutic drugs
  • PC=lecithin
  • Lecithin/sphingomeylin ratio in amniotic fluid as an indicator of fetal lung maturity. Ratio <2.0, risk of RDS
  • reduces surface tension
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11
Q

Plasmalogens

A

Same as PC, PS, or PE EXCEPT

  • acyl group in PC; alkenyl group in Plasmalogens
  • attached via an ester bond in PC; attached via an ether bond in Plasmalogens
  • Plasmalogens found in myelin and heart muscle
  • Platelet activating factor (PAF) is a plasmalogen in which an alkyl (not alkenyl) moietyis attached via an ether bond to carbon 1 of the glycerol
    • C2 of the glycerol is esterified to an acetyl group
    • PAF are released by phagocytes to
      • aggregation
      • edema, hypotension, and involvedin allergicrxn
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12
Q

Degradation of Phospholipids

A
  • Phospholipases A1, A2, C, and D hydrolyze phosphoglycerides
    *
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13
Q

Sphingomyelin synthesis

A
  • Palmityl CoA + Serine –> CO2 + CoA –(3 ketosphinganine) + NADPH + H+–> NADP+ –(sphinganine) + FAD–> FADH2 + Sphingosine
  • Sphingosine + Fatty acyl CoA —> Ceramide + CoA
  • Ceramide + CDP-choline —> Sphigomyelin + CMP
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14
Q

Sphingomyelin Degradation

A
  • Sphingomyelin –(Sphingomyelinase)–> Ceramide + phosphorylcholine
  • Ceramide –(Ceramidase)–>Sphingosine + free FA
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15
Q

Glycospingolipids aka glycolipids

A
  • derived from ceramides
  • head group = monosaccharide (s) or oligosaccharides (via glycosidic linkage)
    • no phosphate
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16
Q

Neutral glycosphingolipid (glycolipid)

A
  • head group is a monosaccharide or oligosaccharide–neutral
  • Cereboside monosaccharides:
    • galactocerebroside (ceramide + galactose)
    • glucocerebroside (ceramide + glucose
  • Cerebroside oligosaccharide (globosides)
    • found in brain and peripheral nervous tissue
    • highly concentrated in myelin sheath
17
Q

Acidic Glycospingolipids (glycolipids)

A
  • At physiologic pH, carry a negative charge provided either by N-acetylneuraminic acid (NANA) or by sulfate group
    • gangliosides: found primarily in ganglion cells of CNS
      • ceramide oliogosaccharides w/ one or more NANA
        • GM1, GM2, GM3
        • Accumulation can lead to lipid storage diseases
    • Sulfatides: galactocerebrosides in which galactose residue has been sulfated
      • found in nervous tissue
18
Q

Functions of glycospingolipids (glycolipids)

A
  • components of cell membrane (outer lipid bilayer)
  • most abundant in nervous tissues
  • cell surface receptors (cholera & diphtheria)
  • involved in cell growth and proliferation
  • genetic disorders for accumulation of these lipids result in impairment of nervous system
  • blood group antigens
19
Q

Features of glycospingolipid catabolism

A
  • all rxns in lysosome
  • enzymes are hydrolyzes
  • optimal pH acidic 3.4-5.5
20
Q

Synthesis of Glycospingolipids (glycolipids)

A
  • synthesized in the golgi and ER by the addition of glycosyl residues to the acceptor molecule by glycosyl transferases
21
Q

Degradation of Glycospingolipids

A
  • degraded by lysosomal enzymes
  • Ganglioside GM1 –(ß Galactosidase) –> Ganglioside GM2
  • Ganglioside GM2 –(Hexosaminidase A)–> Hematoside GM3
  • Hematoside GM3 –(Neuraminidase)–> Lactosyl ceramide
    • Globoside –(Hexosaminidase B/A)–> Ceramide trihexoside
    • Ceramide trihexoside –(alpha-galactosidase A)–> Lactosyl ceramide
  • Lactosyl ceramide –(ß Galactosidase)–>Glc-Cer
  • Glc-Cer –(ß Glucosidase)–> Cer
    • Choline-P-Cer sphingomyelin –(sphingomyelinase)–>Cer
    • Cer-Gal-SO3- –(Arylsulfatase A)–> galactocerebroside
    • galactocerebroside –(ß galactosidase I)–>Cer
  • Cer –(ceramidase)–>Sphingosine + FA
22
Q

Lipid Storage Diseases

A
23
Q

Tay Sach’s vs. Sandoff’s

A
24
Q

Tay Sachs Disease

A
  • Hexosaminidase A deficiency
  • Infantile form
    • macrocephaly
    • ataxia
    • hepatosaplenomegaly
    • macular pallor w/ cherry-red spot on retina
  • Juvenile-onset
    • dementia & ataxia
  • Adult-onset
    • childhood clumsiness
    • progressive motor weakness
    • dementia
25
Q

Gaucher’s diease

A
  • Glucosidase deficiency
  • Glucocerebroside accumulation
  • hepatosplenomegaly
  • seizures
  • Aseptic necrosis (bone death)
  • Slow, progressive mental retardation
  • Generalized dementia
26
Q

Nimann-Pick Disease

A
  • Spingomyelinase deficiency
  • accumulation of sphingomyelins
  • Hepatosplenomegaly
  • metanl retardation
  • Progressive pulmonary disease
  • macular degeneration
  • early death
27
Q

Metachromatic Leukodystrophy

A
  • Arylsulphatase A deficiency
  • Accumulation of sulfatides
  • demyelination neurons
  • mental retardation
  • Loss of cognitive functions
  • Ataxia
  • Optic atrophy
28
Q
A