complex lipids Flashcards
1
Q
lipids
A
diverse and ubiquitous group of organic compounds that are insoluble in water but soluble in organic solvents
2
Q
lipid classification
A
lipids
- glycerol based (glycerol backbone)
- none glycerol based (waxes, steroids, sphingolipids, glycosphingolipids
3
Q
glycerol based lipids classification
A
- simple (fats and oils, glycerol + 3 FA)
- compound/complex (phospholipids, glycolipids)
4
Q
glycerol with a simple sugar attached
A
glycoprotein
5
Q
glycerophospholipids
A
hydrophobic tail, glycerol backbone, polar head
2 FA attached
6
Q
sphingophospholipids
A
- shingomyelin
- polar head group
- backbone is amino alcohol
7
Q
What is the only lipid that is also sphingophospholipid
A
sphingomyelin
8
Q
what is the back bone made of in sphingophospholipids?
A
amino acids
9
Q
hydrophilic head of phospholipids
A
phosphate group and glycerol backbone
10
Q
hydrophobic tails of phospholipids
A
fatty acid hydrocarbon tails
11
Q
phospholipid structure
A
amphipathic
12
Q
arrangement of phospholipids
A
different depending on
- type of phospholipid
- types of FA
- level of saturation
13
Q
phospholipid arrangement in water
A
hydrophilic heads out and hydrophilic tails in
- arrange in this way to form the lipid bilayer
- spontaneous
14
Q
phospholipid functions
A
-serve as major structural component of all biological molecules and as part of the membranes and other compounds
15
Q
Where are the hydrophobic heads of the phospholipid arranged at?
A
inner and outer surface of the bilayer
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)
17
Q
as part of the membrane, phospholipids function as…
A
- reservoir for intracellular second messengers
- anchor point for membrane proteins
18
Q
what are some intracellular second messengers associated with phospholipids?
A
- PIP2
- IP3
- DAG
- ceramide
- sphingosine
- sphingosine 1-phosphate
19
Q
phospholipids serve as components for…
A
- lipoprotein particles (chylomicrons, VLDL, LDL, HDL)
- pulmonary surfactants
- bile
20
Q
phospholipids and dry eye
A
> 60nm thick tear film
21
Q
phospholipids and cataracts
A
lower PL in lens with cataracts
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
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
24
Q
phosphatidylcholine (PC, lecithin)
A
- first found in egg
- PC=PA + choline
- MOST ABUNDANT
- storage for choline
- lung surfactant (DPPC)
25
lung surfactant
90% lipids and 10% proteins
26
what does lung surfactant play a role in?
- decrease surface tension of the extracellular fluid layer covering the alveoli
- reduces the pressure needed to re-inflate alveoli
- prevents alveolar collapse
27
atelectasis
lung collapse
28
Respiratory distress syndrome (RDS)
- in preterm infants due to insufficient lung surfactant
- death
- can be in adults if there is damage or trauma
29
phosphatidylethanolamine (PE, cephalin)
- neuronal tissue
- PE=PA + ethanolamine
- 2ND MOST ABUNDANT
- synthesis of phosphatidylserine
30
phosphatidylserine (PS)
- PS=PA + serine
- less abundant
- found in the inner leaflet of the plasma membrane
- required for membrane synthesis
- role in recognition of apoptotic cells
31
phosphatidyllinositols (PLs)
- PI=PA+inositol
- unusual lipid
- reservoir for arachidonic acid
- can produce important precursors for second messenger molecules (PIP2)
32
What is a precursor for prostaglandins?
phosphatidylinositols (Pls) because they serve as reservoirs for arachidonic acid
33
Why is phosphatidylinositols (Pls) unique?
contains stearic acid at C1 and arachidonic acid at C2
34
How can phosphatidylinositols be used as precursors for second messenger molecules?
-OH groups can be phosphorylated
35
What is a substrate for PLC?
What does it produce?
what glycophospholipid plays a role in it?
- PIP2
- IP3 and DAG (cell signaling cascades)
- phosphatidylinositols
36
which PI is important in the retina?
phosphatidylinositols are very investigated in retina cells with important functions in photoreceptors
37
phosphatidylglycerol (PG)
- PG=PA+glycerol
- precursor for surfactant
- precursor for cardiolipin
38
What PL responsible for lung surfactant
- phosphatidylglycerol (PG)
| - phosphatidylcholine (PC)
39
cardiolipin (diphosphatidylglycerol)
- 2 PA molecules esterified
- exclusive to the inner mitochondrial membrane
- maintains the structure and function of ETC complexes
- maintains proton gradient
40
ether glycerophospholipids FA attachment
-FA is attached via ETHER linkage
41
ether glycerophospholipid types
- plamalogens (unsat FA at C1)
| - platelet-activating factor (PAF)
42
plasmalogens
- ether glycerophospholipids
- phosphatidALcholine (hearts)
- phosphatidALethanolamine (nerve)
43
platelet-activating factor (PAF)
- 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
44
What is one of the most potent bioactive molecules?
platelet-activating factor (PAF)
| -triggers thrombotic and inflammatory events
45
Where does glycerophospholipid synthesis take place?
- most lipids: smooth ER--Golgi---transport vesicles---other membranes
- ether lipids: peroxisomes
46
synthesis of phosphatidic acid (PA)
- 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
second step of GLP synthesis
- 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
CDP-DAG pathway
- in GLP synthesis, PA serves as precursor in this
| - used for PI, PG, and cardiolipin
49
Transfer of CDP-choline or CDP-ethanolamine to DAG
- in GLP synthesis, PA serves as precursor for this
- PC, PE
- kennedy pathway
50
Where do choline and ethanolamine originate from?
diet
51
synthesis of PS
- PE is used as a substrate for the synthesis of PS
- base exchange reaction
- reversible step but primarily used to produce PS
52
synthesis of PC from PS and PE in the liver
- PS is decarboxylated to form PE
| - PE is methylated in 3 subsequent steps using methyl donors (SAM)
53
What does liver require in the synthesis of PC from PS and PE?
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
phospholipases (PLPs)
- 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
What is the only sphingolipid that is also a phospholipid?
sphingomyelin
56
fatty acid + sphingosine
ceramide
57
glycospingolipids
- major component of brain tissue
| - mono- or oligo- saccharide attached=gangliosides and cerebrosides
58
gangliosides and cerebrosides
glycophospholipid with mono- or oligo-saccharide attched
59
what is a the universal component of all membranes?
glycosphingolipids
60
what are the precursors of bioactive lipids (second messengers)?
glycosphingolipids
61
what kind of backbone does sphingosine have?
amino, no glycerol
62
what is the most abundant sphingolipid?
sphingomyelin (SM)
63
What is sphingomyelin composed of?
ceramide + phosphocholine (head group)
64
Major structural sphingolipid in the plasma membrane
- SM
- lipid raft formation
- role in signaling as precursor for the bioactive ceramide
65
What sphinolipid is abundant in nerve tissue?
sphingomyelin.
| constituent of myelin sheath
66
What are the major sphingolipids?
sphingomyelin (SM)
Ceramides (Cer)
sphingosine
67
what is ceramide made up of?
sphingosine+ FA
68
What is the precursor for SM and all glycosphingolipids?
ceramide
| can be produced from the breakdown of these two
69
How do ceramides differ from other molecules?
differ in the type of FA attached to sphingosine
70
What glycosphingolipid is a bioactive second messenger?
cermide. plays a role in cell signalling
71
ceramides role in skin
- maintaining the skin's water-permeability barrier
- polyunsaturated, long chain
- decreased levels are associated with a number of skin diseases
72
what are the major glycosphingolipids?
```
neutral GSLs (cerebrosides)
acidic GSLs
```
73
what makes up sphingosine
palmitic acid + serine
| NO FATTY ACID, can exist on its own
74
What is the precursor for sphingosine 1-P?
sphingosine
| potent bioactive second messenger recognized by atleast 5 different GPCR
75
Sphingosine and the eye
controls endocytosis of rhodopsin and another light sensitive eye protein, the transient receptro potential (TRP) channel
76
sphingolipids in the eyes
- present in normal tensive aqueous
- absent in hypertensive aqueous humor
- elevated IOP and glaucoma
77
Cherry Red Macula
- Tay-Sachs (gangliosides)
- Sadnhoff (similar to TS)
- Nieman-Pick (A and B)
78
glycosphingolipids role
- cellular interactions
| - growth and development
79
GSLs and transformed cells (cancer)
dramatically change their plasma membrane GLS composition
80
Antigenic property of GSL
- 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
cerebroside
- 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
make up of cerbroside
```
Ceramide + sugar
(mono or di)
-galactosylceramide (GLYCOSIDIC LINK)
-glucosylceramide
-lactosylceramide
```
83
What are acidic GSLs?
- gangliosides
- sulfatides
negatively charged at pH 7
84
ganglioside
- 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
sulfatides
- acidic GSL
- galactocerebroside + -SO3- group
- brain and kidney
86
Where does sphingolipid synthesis begin?
ER
87
What is the first thing that happens in sphingolipids synthesis?
condensation of palmitoyl CoA and L-serine catalyzed by serine palmitoyl transferase (SPT)
88
What is the rate limiting step in synthesis of sphingolipids?
condensation of palmitoyl CoA and L-serine catalyzed by serine palmitoyl transferase (SPT)
-requires PLP as coenzyme
89
What does SPT require?
PLP as coenzyme
90
What forms the sphingoid backbone and produce ceramide?
-several subsequent steps: reduction of the product; addition of a FA and desaturation of one of the C-C bonds
91
Where is ceramide transferred to during sphingolipid synthesis?
Golgi
used as a substrate for the synthesis of
-sphingomyelin (SM-synthase)
- GSL (glycosyltransferases)
92
What enzyme produces SM from ceramide?
SM-sythase
93
what type of enzyme produces GSL from ceramide?
glycosyltransferases
94
where so SM and GSL go from the Golgi?
distributed to all membranes via vesicular transport or incorporated and secreted into lipoproteins
95
lipoproteins from SM and GSL
SM and GSL go to Golgi and secreted into these in the liver and gut
96
local (limited) degradation of SM
- in the plasma membrane by neutral sphingomyelinases
- produce ceramide
- play a role in cell signalling
97
completel degradation of SM and GSLs
- internalized via endocytotic pathways in the lysosomes
| - different acidic enzymes with optimal pH=4.5
98
acidic enzymes that can play a role in the complete degradation of SM and GSL
- sphingomyelinase
- ceramidase
- a-galactosidase
- B-galactosidase
- B-hexosaminase A
- B-hexosaminase B
- Arylsulfatase A
99
sphingolipidoses overview
- deficiency in an of the acicid enxymes results in particular lipid storage disease
- accumulation
100
sphingolipid synthesis and degradation
in healthy state, they are balanced tightly so that amounts of these compounds are at constant levels
101
What causes SL substrate to accumulate?
if a particular acid hydrolase is defective or missing
102
location that shingilipidoses affects most
nervous tissue
| -progressive disorder
103
severity of the mutation in sphingolipidoses
- may be fatal in early life
| - may have extensive phenotypic variability
104
incidence of sphingolipidoses
low, except
- Tay;Sachs
- Gaucher
- Niemenn-Pick diseases
affect more frequent in the Ashkenazi Jewish population
105
Tay-Sachs
- Hexosaminidase A deficient
- ganglioside accumulates
- mental retardation, blindness, muscular weakness, cherry red macula
106
Fabry's disease
- a-galactosidase deficient
- globotriaosylceramide accumulates
- skin rash, kidney failure
107
Metachromatic leukodystrophy
- arylsulfatase A deficient
- 3-sulfogalactosylceramide accumulates
- mental retardation, psychological disturbances in adults; demyelination
108
Krabbe's disease
- B-galactosidase deficient
- galactosylceramide accumulates
- mental retardation, myelin almost absent
109
Gaucher's disease
- B-gucosidase deficient
- glucosylceramide accumulates
- enlarged liver and spleen, erosion of long bones, mental retardation in infants
110
Niemann-Pick disease
- Sphingomyelinase deficient
- Sphingomyelin accumulates
- enlarged liver and spleen, mental retardation, fatal early in life, cherry red macula
111
Farber's disease
- ceramidase deficient
- ceramide accumulation
- hoarsness, dermatitis, skeletal deformation, mental retardation, fatal in early life
112
What diseases have cherry red macula?
- tay sachs
- sadnhoff
- Nieman-pick A and B
