Metabolism of Complex Lipids Flashcards

1
Q

Lipids

A

-diverse and ubiquitous group of organic compounds that are insoluble in water, but soluble in organic solvents

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2
Q

General lipid classification

A
  • glycerol based and none glycerol based

- glycerol backbone and non glycerol backbone

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3
Q

Glycerol based lipid classificaion

A

-simple and complex

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4
Q

None glycerol based lipids

A
  • waxes
  • steroids
  • sphingolipids(amino and alcohol backbone)
  • glycosphingolipids(major of this group in humans)
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5
Q

Simple glycerol based

A
  • 3 fatty acids

- glycerol backbone

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6
Q

Compouns glycerol based

A
  • phospholipids and glycolipids
  • glycerol backbone
  • 2 fatty acids
  • 1 additional product(phospho group and polar group OR glucose)
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7
Q

Types of phospholipids

A

-glycerophospholipids and sphingophospholipids

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8
Q

Glycerophospholipids

A
  • complex
  • phospholipid
  • 2 fatty acids at position 1 and 2
  • glycerol backbone
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9
Q

Sphingophospholipds

A
  • complex
  • phospholipids
  • Backbone: amino alcohol
  • FA attached to backbone is bromitic acid
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10
Q

Sphingomeylin

A
  • only sphingolipid that also has polar head group

- structural component of plasma membrane

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11
Q

Phospholipid structure

A
  • amphipathic
  • hydrophilic head: phosphate group and backbone
  • Hydrophobic tail: fatty acids and hydrocarbons
  • in water, they arrange so hydrophilic heads are out and hydrophobic tails are in to form a bilayer(formed spontaneously)
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12
Q

Three arrangements of lipid bilayers

A
  • able to separate from other molecules so basically starting point for cells
  • lipid bi-layer sheet
  • lipid bi-layer sphere
  • single layer lipid sphere
  • depends on…
  • type of phospholipids that are prensent
  • the polar head groups
  • the types of FA attacheded(length and saturation)
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13
Q

Phospholipid functions

A
  • structural components
  • reservoir for intracellular second messengers
    - degradation of phospholipids release them
  • anchor for membrane proteins
  • component for lipoprotein particles(chylomimcrons, VLDL)
  • component for pulmonary surfactants(secrete epithelial cells)
  • component for bile
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14
Q

Phospholipids and tears

A
  • layer tear structure
  • PC, PE and SM are major ones used
  • thinning of this layer leads to evaporation of tears and dry eye
  • decreased PL found in cataracts
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15
Q

Phosphatidic acid (PA)

A
  • glycerophospholipid
  • precursor for synthesis of other glycerophospholipids and TAG
  • signaling molecule
  • influence membrane curvature
  • transfer vesicles from molecules
  • simple!!!!
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16
Q

Phosphatidycholine (PC)

A
  • lecithin
  • PC=PA+Choline
  • most abundant phospholipid
  • storage for choline
  • component of lung surfactant(DPPC)
  • eggs
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17
Q

Lung Surfactant

A
  • 90% lipids, 10% proteins
  • decreases surface tension of extracellular fluid covering the alveoli
  • reduces pressure needed to re-inflate alveoli
  • prevents atelectasis(alveolar collapse)
  • DPPC is most abundant phospholipid
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18
Q

Respiratory Distress Syndrome

A
  • RSD
  • infants
  • insufficient lung surfactant
  • lung surfactant is formed at 32 weeks, so premies dont have it.
  • mom is given cholic acid before to help
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19
Q

Phosphatidylethanolamine(PE)

A
  • PE=PA+ethanolamine
  • second most abundant
  • synthesis of phosphatidylserine in reaction with free serine
  • nervous tissue
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20
Q

Phosphatidylserine(PS)

A
  • PS=PA+Serine
  • only found in inner leaflet of the plasma membrane
  • required for membrane synthesis
  • recognizes apoptotic cells
    • when exposed in outermembrane, it shows that cell is dying an signals macrophages to clean it up
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21
Q

Phosphatidylinositols (Pls)

A

Pl=PA+inositol

  • contains stearic acid at C1 and arachidonic acid at C2
  • reservoir for arachidonic acid
  • precursor for prostaglandins
  • OH group can be phosphorylated to produce secondary messengers
  • in retina cells for photoreception
22
Q

Phosphatidylglycerol (PG)

A
  • PG=PA+ glycerol
  • recursor for surfactant
  • presence in amniotic fluid indicated fetal lung maturity
  • precursor for cardiolipin
23
Q

Cardiolipin

A
  • 2 PA molecules esterified through phosphate groups
  • ONLY IN INNER MITOCHONDRIAL MEMBRANE
  • MAINTAINS STRUCTURE AND FUNCTION OF ETC COMPLEXES
24
Q

Ether glycerophospholipids

A
  • FA at position 1 via ETHER linkage

- 2 types based on the saturation of FA at position 1

25
Q

Plasmalogens

A
  • ether glycerophospholipid

- unsaturated FA at position 1

26
Q

Phosphatidalcholine

A

-plasmalogen in heart muscle

27
Q

Phosphatidalethanolamine

A

-plasmalogen in nerve tissue

28
Q

Platelet-aggregating factor (PAF)

A
  • ether glycerophospholipid
  • saturated FA at position 1
  • short acetyl group at position 2 (NOT ACYL GROUP)
  • synthesized and released by variety of cell types
  • most potent bioactive molecule: triggers thrombotic and inflammatory events
  • mediates anaphylaxis and hypersensitivity
29
Q

Locations of glycerophospholipids

A

-always associated with the membrane and need a transporter to move
Most lipids: Smooth ER–>golgi(packaged/modified)–>transport vesicles–>other membranes
Ether lipids: peroxisomes

30
Q

Synthesis of phosphatidic acid (PA)

A
  • all cells EXCEPT mature erythrocytes can synthesize PA from…
  • glycerol 3 phosphate
  • 2 fatty acyl CoA

-any cells with ER can synthesize phospholipids

31
Q

CDP-DAG pathway

A

-used for synthesis of PI,PG and cardiolipin

32
Q

Transfer of activated CDP-choline or CDP-ethanolamine to DAG

A
  • kennedy pathway
  • synthesis of PC and PE
  • choline and ethanolamine originate from diet and are primarily for liver
33
Q

Synthesis of PS

A
  • PE is used as a substrate
  • base exchange reaction
  • reversible step, but primarily only moves to produce PS
34
Q

Synthesis of PC from PS and PE in the liver

A
  • PS decarboxylated to form PE
  • PE methylated in 3 steps using methyl donors
  • liver requires secondary mechanism to produce PC even when free choline levels are low because…
    • PC is secreted out of liver in bile
    • PC are incorporated into lipoproteins and secreted
35
Q

Phospholipase (PLP)

A
  • hydrolyze phosphodiester bond of glycerophospholipids
  • site specific cleavage(can only cleave at position 2)
  • release bioactive molecules that act as secondary messengers(DAG,IP3)
  • participate in remodeling pf phospholipids together with fatty acyl CoA transferases
36
Q

Sphingolipids structure

A
  • major component of brain and nervous tissues
  • structural component of membranes and some bioactive lipids (DAG and secondary messengers)
  • amino alcohol backbone
37
Q

Sphingomyelin

A

Ceramide + phosphocholine(polar head group)

  • most abundant sphingophospholipid in mammals
  • abundant in nerve tissues and myelin sheath
  • role in lipid raft formation
  • signaling as a precursor for bioactive ceramide
38
Q

Lipid raft

A

-clusters of lipids, cholesterol, and sphingomyelin used for cell signaling

39
Q

Ceramimdes

A
  • sphingosine+fatty acid
  • diverse group that differ in the type of FA attached to sphingosine
  • precursor for SM and all glycosphingolipids
  • bioactive second messener
  • maintain skin’s water-permeability barrier
40
Q

Sphingosine

A

palmitic acid+ serine

  • bioactive second messenger
  • precursor for sphingosine 1P
  • no FA, just backbone
41
Q

Sphingosine 1P

A
  • bioactive second messenger recognized by GPCR

- controls endocytosis of rhodopsin and eye proteins and TRP channel

42
Q

Glycosphingolipids in human cells

A
  • play role in cellular interactions and growth and development
  • transformed cells (cancer) change their plasma membrane glycosphingolipid composition
43
Q

Antigenic

A
  • carbohydrate portion of a glycolipid is the antigenic determinant
  • source of blood group antigens
  • function as antigens in embryonic development
  • tumor antigens
  • serve as cell surface receptors for toxins
44
Q

Neutral GSLs

A
  • cerebrosides
  • ceramide+sugar
  • galactosylceramide, glucosylceramide, lactosylceramide
  • essential component of membranes(mostly on outer leaflet)
  • lipid raft formation
  • mostly in brain and peripheral tissues
45
Q

Acidic GSL

A
  • gangliosides
  • CER+oligosaccharode+NANA
  • found in ganglion cells in CNS
  • negatively charged at pH 7
  • lipid storage diseases lead to accumulation of these lipids
46
Q

Sulfatides

A
  • Acidic
  • galactocerebroside+SO3 group
  • found in kidney and brain
47
Q

Sphingolipid synthesis step 1

A
  • begins in ER with condensation of palmitoyl CoA and L-serine
  • uses serine palmitoyl transferase
  • rate limiting step
  • needs PLP as coenzyme
48
Q

Sphingolipid synthesis middle

A
  • several steps to form sphingoid backbone and produce ceramide
  • ceramide is transferred to Golgi and used as synthesis of sphingomyelin and glycosphingolipids
  • from golgi to distributed to membranes by vesicular transport OR into lipoproteins in liver and gut
49
Q

Sphingolipid degradation

A

-local degradation of SM in PLASMA MEMBRANE by neutral sphingomyelinases to produce ceramide

50
Q

Complete degradation of SM and GSL

A
  • internalized via endocytotic pathways in the LYSOSOMES by acidic enzymes with optimal pH of 4.5
  • and deficiencies in ANY enzymes results in sphingolipidoses
51
Q

Healthy state

A

-sphingolipid synthesis and degradation are balanced tightly so that compounds are at constant levels

52
Q

Sphingolipidoses

A
  • if particular acid hydrolase is defective, SL substrate accumulates
  • disorders are progressive and mainly in nervous systems
  • autosomal recessive
  • genetic variability
  • incident of sphingoipidoses is low in most populations