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Biochem BLOCK 2 > complex lipids > Flashcards

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

lipid classification

A

lipids

  • glycerol based (glycerol backbone)
  • none glycerol based (waxes, steroids, sphingolipids, glycosphingolipids
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3
Q

glycerol based lipids classification

A
  • simple (fats and oils, glycerol + 3 FA)

- compound/complex (phospholipids, glycolipids)

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4
Q

glycerol with a simple sugar attached

A

glycoprotein

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5
Q

glycerophospholipids

A

hydrophobic tail, glycerol backbone, polar head

2 FA attached

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6
Q

sphingophospholipids

A
  • shingomyelin
  • polar head group
  • backbone is amino alcohol
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7
Q

What is the only lipid that is also sphingophospholipid

A

sphingomyelin

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8
Q

what is the back bone made of in sphingophospholipids?

A

amino acids

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9
Q

hydrophilic head of phospholipids

A

phosphate group and glycerol backbone

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10
Q

hydrophobic tails of phospholipids

A

fatty acid hydrocarbon tails

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11
Q

phospholipid structure

A

amphipathic

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12
Q

arrangement of phospholipids

A

different depending on

  • type of phospholipid
  • types of FA
  • level of saturation
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13
Q

phospholipid arrangement in water

A

hydrophilic heads out and hydrophilic tails in

  • arrange in this way to form the lipid bilayer
  • spontaneous
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14
Q

phospholipid functions

A

-serve as major structural component of all biological molecules and as part of the membranes and other compounds

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15
Q

Where are the hydrophobic heads of the phospholipid arranged at?

A

inner and outer surface of the bilayer

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16
Q

where are the hydrophobic tails of phospholipids arranged at?

A

associates with the non polar portions of other membrane constituents (glycolipids, proteins and cholesterol)

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17
Q

as part of the membrane, phospholipids function as…

A
  • reservoir for intracellular second messengers

- anchor point for membrane proteins

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18
Q

what are some intracellular second messengers associated with phospholipids?

A
  • PIP2
  • IP3
  • DAG
  • ceramide
  • sphingosine
  • sphingosine 1-phosphate
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19
Q

phospholipids serve as components for…

A
  • lipoprotein particles (chylomicrons, VLDL, LDL, HDL)
  • pulmonary surfactants
  • bile
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20
Q

phospholipids and dry eye

A

> 60nm thick tear film

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21
Q

phospholipids and cataracts

A

lower PL in lens with cataracts

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22
Q

glycerophospholipids in humans

A
  • phosphatidic acid (PA)
  • phosphatidylcholine (PC, lecithin)
  • phosphatidylethanolamine (PE, cephalin)
  • phosphatidylserine (PS)
  • phosphatidylinositols (Pls)
  • phosphatidylglycerol (PG)
  • cardiolipin (diphosphatidylglycerol)
  • ether glycerophospholipids
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23
Q

phosphatidic acid (PA)

A
  • simplest of all PL
  • a precursor for he synthesis of all other glycerophospholipids and TAG
  • signaling molecule
  • influence membrane curvature and vesicle formation
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24
Q

phosphatidylcholine (PC, lecithin)

A
  • first found in egg
  • PC=PA + choline
  • MOST ABUNDANT
  • storage for choline
  • lung surfactant (DPPC)
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25
Q

lung surfactant

A

90% lipids and 10% proteins

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26
Q

what does lung surfactant play a role in?

A
  • decrease surface tension of the extracellular fluid layer covering the alveoli
  • reduces the pressure needed to re-inflate alveoli
  • prevents alveolar collapse
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27
Q

atelectasis

A

lung collapse

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28
Q

Respiratory distress syndrome (RDS)

A
  • in preterm infants due to insufficient lung surfactant
  • death
  • can be in adults if there is damage or trauma
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29
Q

phosphatidylethanolamine (PE, cephalin)

A
  • neuronal tissue
  • PE=PA + ethanolamine
  • 2ND MOST ABUNDANT
  • synthesis of phosphatidylserine
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30
Q

phosphatidylserine (PS)

A
  • PS=PA + serine
  • less abundant
  • found in the inner leaflet of the plasma membrane
  • required for membrane synthesis
  • role in recognition of apoptotic cells
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31
Q

phosphatidyllinositols (PLs)

A
  • PI=PA+inositol
  • unusual lipid
  • reservoir for arachidonic acid
  • can produce important precursors for second messenger molecules (PIP2)
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32
Q

What is a precursor for prostaglandins?

A

phosphatidylinositols (Pls) because they serve as reservoirs for arachidonic acid

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33
Q

Why is phosphatidylinositols (Pls) unique?

A

contains stearic acid at C1 and arachidonic acid at C2

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34
Q

How can phosphatidylinositols be used as precursors for second messenger molecules?

A

-OH groups can be phosphorylated

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35
Q

What is a substrate for PLC?
What does it produce?
what glycophospholipid plays a role in it?

A
  • PIP2
  • IP3 and DAG (cell signaling cascades)
  • phosphatidylinositols
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36
Q

which PI is important in the retina?

A

phosphatidylinositols are very investigated in retina cells with important functions in photoreceptors

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37
Q

phosphatidylglycerol (PG)

A
  • PG=PA+glycerol
  • precursor for surfactant
  • precursor for cardiolipin
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38
Q

What PL responsible for lung surfactant

A
  • phosphatidylglycerol (PG)

- phosphatidylcholine (PC)

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39
Q

cardiolipin (diphosphatidylglycerol)

A
  • 2 PA molecules esterified
  • exclusive to the inner mitochondrial membrane
  • maintains the structure and function of ETC complexes
  • maintains proton gradient
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40
Q

ether glycerophospholipids FA attachment

A

-FA is attached via ETHER linkage

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41
Q

ether glycerophospholipid types

A
  • plamalogens (unsat FA at C1)

- platelet-activating factor (PAF)

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42
Q

plasmalogens

A
  • ether glycerophospholipids
  • phosphatidALcholine (hearts)
  • phosphatidALethanolamine (nerve)
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43
Q

platelet-activating factor (PAF)

A
  • ether glycerophospholipids
  • sat FA at C1 and short acetyl group at C2
  • synthesized and released by variety cell types
  • one of the most potent bioactive molecules
  • mediate anaphylaxis and hypersensitivity
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44
Q

What is one of the most potent bioactive molecules?

A

platelet-activating factor (PAF)

-triggers thrombotic and inflammatory events

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45
Q

Where does glycerophospholipid synthesis take place?

A
  • most lipids: smooth ER–Golgi—transport vesicles—other membranes
  • ether lipids: peroxisomes
46
Q

synthesis of phosphatidic acid (PA)

A
  • first step of GPL synthesis
  • essentially all cells except mature erythrocyte can synthesize PA from:
    • glycerol 3-P
    • 2 fatty acyl CoA-added in 2 subsequent reactions
47
Q

second step of GLP synthesis

A
  • once PA is produced, it serves as a precursor for PL synthesis by different pathways
    • CDP-DAG pathway
    • transfer of CDP-choline or CDP- ethanolamin to DAG
48
Q

CDP-DAG pathway

A
  • in GLP synthesis, PA serves as precursor in this

- used for PI, PG, and cardiolipin

49
Q

Transfer of CDP-choline or CDP-ethanolamine to DAG

A
  • in GLP synthesis, PA serves as precursor for this
  • PC, PE
  • kennedy pathway
50
Q

Where do choline and ethanolamine originate from?

A

diet

51
Q

synthesis of PS

A
  • PE is used as a substrate for the synthesis of PS
  • base exchange reaction
  • reversible step but primarily used to produce PS
52
Q

synthesis of PC from PS and PE in the liver

A
  • PS is decarboxylated to form PE

- PE is methylated in 3 subsequent steps using methyl donors (SAM)

53
Q

What does liver require in the synthesis of PC from PS and PE?

A

the secondary mechanism to produce PC even when free choline levels are low because significant amounts of PC

  • are secreted from liver cells in the bile
  • are incorporated into lipoproteins and secreted
54
Q

phospholipases (PLPs)

A
  • GPL degradation and remodeling
  • hydrolyze the phosphodiester bonds of GPL
  • site specific cleavage
  • release bioactive molecules (can serve as second messengers such as DAG and IP3)
  • participate in remodeling of PL with FA CoA transferases
55
Q

What is the only sphingolipid that is also a phospholipid?

A

sphingomyelin

56
Q

fatty acid + sphingosine

A

ceramide

57
Q

glycospingolipids

A
  • major component of brain tissue

- mono- or oligo- saccharide attached=gangliosides and cerebrosides

58
Q

gangliosides and cerebrosides

A

glycophospholipid with mono- or oligo-saccharide attched

59
Q

what is a the universal component of all membranes?

A

glycosphingolipids

60
Q

what are the precursors of bioactive lipids (second messengers)?

A

glycosphingolipids

61
Q

what kind of backbone does sphingosine have?

A

amino, no glycerol

62
Q

what is the most abundant sphingolipid?

A

sphingomyelin (SM)

63
Q

What is sphingomyelin composed of?

A

ceramide + phosphocholine (head group)

64
Q

Major structural sphingolipid in the plasma membrane

A
  • SM
  • lipid raft formation
  • role in signaling as precursor for the bioactive ceramide
65
Q

What sphinolipid is abundant in nerve tissue?

A

sphingomyelin.

constituent of myelin sheath

66
Q

What are the major sphingolipids?

A

sphingomyelin (SM)
Ceramides (Cer)
sphingosine

67
Q

what is ceramide made up of?

A

sphingosine+ FA

68
Q

What is the precursor for SM and all glycosphingolipids?

A

ceramide

can be produced from the breakdown of these two

69
Q

How do ceramides differ from other molecules?

A

differ in the type of FA attached to sphingosine

70
Q

What glycosphingolipid is a bioactive second messenger?

A

cermide. plays a role in cell signalling

71
Q

ceramides role in skin

A
  • maintaining the skin’s water-permeability barrier
  • polyunsaturated, long chain
  • decreased levels are associated with a number of skin diseases
72
Q

what are the major glycosphingolipids?

A 
neutral GSLs (cerebrosides)
acidic GSLs
73
Q

what makes up sphingosine

A

palmitic acid + serine

NO FATTY ACID, can exist on its own

74
Q

What is the precursor for sphingosine 1-P?

A

sphingosine

potent bioactive second messenger recognized by atleast 5 different GPCR

75
Q

Sphingosine and the eye

A

controls endocytosis of rhodopsin and another light sensitive eye protein, the transient receptro potential (TRP) channel

76
Q

sphingolipids in the eyes

A
  • present in normal tensive aqueous
  • absent in hypertensive aqueous humor
  • elevated IOP and glaucoma
77
Q

Cherry Red Macula

A
  • Tay-Sachs (gangliosides)
  • Sadnhoff (similar to TS)
  • Nieman-Pick (A and B)
78
Q

glycosphingolipids role

A
  • cellular interactions

- growth and development

79
Q

GSLs and transformed cells (cancer)

A

dramatically change their plasma membrane GLS composition

80
Q

Antigenic property of GSL

A
  • carbohydrate portion of a glycolipid is the antigenic determinent
  • source of blood group antigens
  • function as antigens in embryonic development
  • tumor antigens
  • serve as cell surface receptors for cholera and tetanus toxin, certain viruses and microbes
81
Q

cerebroside

A
  • neutral GSL
  • ceramide + sugar
  • essential component of membranes, mostly found on the outer leaflet of the plasma membrane
  • participate in lipid raft formation
  • nerve tissue (brain and periphery)
82
Q

make up of cerbroside

A 
Ceramide + sugar
(mono or di)
-galactosylceramide (GLYCOSIDIC LINK)
-glucosylceramide
-lactosylceramide
83
Q

What are acidic GSLs?

A
  • gangliosides
  • sulfatides

negatively charged at pH 7

84
Q

ganglioside

A
  • acidic GSL
  • Cer + oligosaccharide + NANA
  • found primarily in the gnaglion cells in the CNS
  • medically important because several lipid storage disorders lead to accumulation of these lipids
85
Q

sulfatides

A
  • acidic GSL
  • galactocerebroside + -SO3- group
  • brain and kidney
86
Q

Where does sphingolipid synthesis begin?

A

ER

87
Q

What is the first thing that happens in sphingolipids synthesis?

A

condensation of palmitoyl CoA and L-serine catalyzed by serine palmitoyl transferase (SPT)

88
Q

What is the rate limiting step in synthesis of sphingolipids?

A

condensation of palmitoyl CoA and L-serine catalyzed by serine palmitoyl transferase (SPT)
-requires PLP as coenzyme

89
Q

What does SPT require?

A

PLP as coenzyme

90
Q

What forms the sphingoid backbone and produce ceramide?

A

-several subsequent steps: reduction of the product; addition of a FA and desaturation of one of the C-C bonds

91
Q

Where is ceramide transferred to during sphingolipid synthesis?

A

Golgi
used as a substrate for the synthesis of
-sphingomyelin (SM-synthase)
- GSL (glycosyltransferases)

92
Q

What enzyme produces SM from ceramide?

A

SM-sythase

93
Q

what type of enzyme produces GSL from ceramide?

A

glycosyltransferases

94
Q

where so SM and GSL go from the Golgi?

A

distributed to all membranes via vesicular transport or incorporated and secreted into lipoproteins

95
Q

lipoproteins from SM and GSL

A

SM and GSL go to Golgi and secreted into these in the liver and gut

96
Q

local (limited) degradation of SM

A
  • in the plasma membrane by neutral sphingomyelinases
  • produce ceramide
  • play a role in cell signalling
97
Q

completel degradation of SM and GSLs

A
  • internalized via endocytotic pathways in the lysosomes

- different acidic enzymes with optimal pH=4.5

98
Q

acidic enzymes that can play a role in the complete degradation of SM and GSL

A
  • sphingomyelinase
  • ceramidase
  • a-galactosidase
  • B-galactosidase
  • B-hexosaminase A
  • B-hexosaminase B
  • Arylsulfatase A
99
Q

sphingolipidoses overview

A
  • deficiency in an of the acicid enxymes results in particular lipid storage disease
  • accumulation
100
Q

sphingolipid synthesis and degradation

A

in healthy state, they are balanced tightly so that amounts of these compounds are at constant levels

101
Q

What causes SL substrate to accumulate?

A

if a particular acid hydrolase is defective or missing

102
Q

location that shingilipidoses affects most

A

nervous tissue

-progressive disorder

103
Q

severity of the mutation in sphingolipidoses

A
  • may be fatal in early life

- may have extensive phenotypic variability

104
Q

incidence of sphingolipidoses

A

low, except

  • Tay;Sachs
  • Gaucher
  • Niemenn-Pick diseases

affect more frequent in the Ashkenazi Jewish population

105
Q

Tay-Sachs

A
  • Hexosaminidase A deficient
  • ganglioside accumulates
  • mental retardation, blindness, muscular weakness, cherry red macula
106
Q

Fabry’s disease

A
  • a-galactosidase deficient
  • globotriaosylceramide accumulates
  • skin rash, kidney failure
107
Q

Metachromatic leukodystrophy

A
  • arylsulfatase A deficient
  • 3-sulfogalactosylceramide accumulates
  • mental retardation, psychological disturbances in adults; demyelination
108
Q

Krabbe’s disease

A
  • B-galactosidase deficient
  • galactosylceramide accumulates
  • mental retardation, myelin almost absent
109
Q

Gaucher’s disease

A
  • B-gucosidase deficient
  • glucosylceramide accumulates
  • enlarged liver and spleen, erosion of long bones, mental retardation in infants
110
Q

Niemann-Pick disease

A
  • Sphingomyelinase deficient
  • Sphingomyelin accumulates
  • enlarged liver and spleen, mental retardation, fatal early in life, cherry red macula
111
Q

Farber’s disease

A
  • ceramidase deficient
  • ceramide accumulation
  • hoarsness, dermatitis, skeletal deformation, mental retardation, fatal in early life
112
Q

What diseases have cherry red macula?

A
  • tay sachs
  • sadnhoff
  • Nieman-pick A and B

Biochem BLOCK 2 (14 decks)

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