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Flashcards in complex lipids Deck (112):
1

lipids

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

2

lipid classification

lipids
-glycerol based (glycerol backbone)
-none glycerol based (waxes, steroids, sphingolipids, glycosphingolipids

3

glycerol based lipids classification

-simple (fats and oils, glycerol + 3 FA)
-compound/complex (phospholipids, glycolipids)

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glycerol with a simple sugar attached

glycoprotein

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glycerophospholipids

hydrophobic tail, glycerol backbone, polar head
2 FA attached

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sphingophospholipids

-shingomyelin
-polar head group
-backbone is amino alcohol

7

What is the only lipid that is also sphingophospholipid

sphingomyelin

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what is the back bone made of in sphingophospholipids?

amino acids

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hydrophilic head of phospholipids

phosphate group and glycerol backbone

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hydrophobic tails of phospholipids

fatty acid hydrocarbon tails

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phospholipid structure

amphipathic

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arrangement of phospholipids

different depending on
-type of phospholipid
-types of FA
-level of saturation

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phospholipid arrangement in water

hydrophilic heads out and hydrophilic tails in
-arrange in this way to form the lipid bilayer
-spontaneous

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phospholipid functions

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

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Where are the hydrophobic heads of the phospholipid arranged at?

inner and outer surface of the bilayer

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where are the hydrophobic tails of phospholipids arranged at?

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

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as part of the membrane, phospholipids function as...

-reservoir for intracellular second messengers
-anchor point for membrane proteins

18

what are some intracellular second messengers associated with phospholipids?

-PIP2
-IP3
-DAG
-ceramide
-sphingosine
-sphingosine 1-phosphate

19

phospholipids serve as components for...

-lipoprotein particles (chylomicrons, VLDL, LDL, HDL)
-pulmonary surfactants
-bile

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phospholipids and dry eye

> 60nm thick tear film

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phospholipids and cataracts

lower PL in lens with cataracts

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glycerophospholipids in humans

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

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phosphatidic acid (PA)

-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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phosphatidylcholine (PC, lecithin)

-first found in egg
-PC=PA + choline
-MOST ABUNDANT
-storage for choline
-lung surfactant (DPPC)

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lung surfactant

90% lipids and 10% proteins

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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

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atelectasis

lung collapse

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Respiratory distress syndrome (RDS)

-in preterm infants due to insufficient lung surfactant
-death
-can be in adults if there is damage or trauma

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phosphatidylethanolamine (PE, cephalin)

-neuronal tissue
-PE=PA + ethanolamine
-2ND MOST ABUNDANT
-synthesis of phosphatidylserine

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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

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phosphatidyllinositols (PLs)

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

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What is a precursor for prostaglandins?

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

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Why is phosphatidylinositols (Pls) unique?

contains stearic acid at C1 and arachidonic acid at C2

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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

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ether glycerophospholipids FA attachment

-FA is attached via ETHER linkage

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ether glycerophospholipid types

-plamalogens (unsat FA at C1)
-platelet-activating factor (PAF)

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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

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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

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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

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fatty acid + sphingosine

ceramide

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glycospingolipids

-major component of brain tissue
-mono- or oligo- saccharide attached=gangliosides and cerebrosides

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gangliosides and cerebrosides

glycophospholipid with mono- or oligo-saccharide attched

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what is a the universal component of all membranes?

glycosphingolipids

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

glycosphingolipids

61

what kind of backbone does sphingosine have?

amino, no glycerol

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what is the most abundant sphingolipid?

sphingomyelin (SM)

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What is sphingomyelin composed of?

ceramide + phosphocholine (head group)

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Major structural sphingolipid in the plasma membrane

-SM
-lipid raft formation
-role in signaling as precursor for the bioactive ceramide

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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

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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