1
Q
structure of glycerophospholipids
A
- predominant phospholipids in cell membranes
- amphipathic with a polar head group attached through at phosphodiester bond to carbon 3 of DAG
- two FA chains form an ester bon to C1 and C2 and are non-polar
- phosphatidic acid is the simplest
- PS, PC, PE
2
Q
cadiolipin
A
- two molecules of phosphatidic acid esterified through their phosphate to a glycerol
- found in membranes of bacteria and eukaryotic cells
- within eukaryotic cells cardiolipin is found in the inner mitochondrial membrane
- supports the structure and function of certain respiratory complexes in the ETC
3
Q
ether glycerophospholipids
A
- in plasmalogens the FA at C1 has an unsaturated alkyl group attached to glycerol by ether linkage (CH=CH instead of C=O)
- acyl group at C2 (FA)
- phosphatidAL ethanolamine-abundant in nerve tissue
- platelet activating factor has saturated alkyl group linked by an ether linkage (CH2-CH2 vs C=O)
- acetyl group at C2 (methyl)
- synthesized by many cells and binds to specific surface receptors stimulating thrombotic and acute inflammatory responses
- phosphatidalvcholine is enriched in heart muscle
- phosphatidalserine and choline are the two most abundant ether lipids in mammals
4
Q
sphingomyelin
A
- backbone is sphingosine
- LCFA attached to amino group through amide bond and makes ceramide
- alcohol at C1 becomes esterified to phosphoryl choline to form sphingomyelin
- only major sphingophospholipid in humans and is found in many membranes
- highly enriched in the myelin sheath wrapped around axons
5
Q
glycosphingolipids
A
- differ from sphingomyelin because they have a sugar attached to the ceramide by an O- glycosidic bond (O-CH2)
- sugar is the polar head group
- ceramide is tail
6
Q
cerebroside
A
- simple uncharged glycosphingolipid with one galactose or glucose
- galactocerebroside
- found in central and peripheral nervous tissue and are enriched in the myelin sheath
7
Q
globosides
A
- ceramide oligosaccharides
- produced by attaching monosacchardies to a glucocerbroside
- ceramide-glu-glc or lactosyl ceramide
- include substituted sugars
- N acetyl galactosamine
8
Q
gangliosides
A
- negatively charged acidic glycosphingolipids
- contain NANA/sialic acid and sulfatides
- derivatives of ceramide oligosaccharides
- contain one or more sialic acid residue,mono,di,tri,quatro
- additional numbers and letter as a subscript designate the sequence of sugars attached to ceramide
- found primarily in ganglion cells of the CNS and are enriched at nerve endings
9
Q
role of complex lipids in membrane structure and function
A
- phospholipids tend to bury the non-polar FA chains within the hydrophobic core of the bilayer or micelle
- asymmetric distribution of lipids
- choline (PC and SM) and glycolipids on outside
- amine containing (PE and PS) and inositol in inner leaflet
- capable of lateral mobility and slower flip flop across membranes
- regulates activity of membrane enzymes and receptors and creating specialized cholesterol, sphingolipid and glycolipid rich lipid rafts
10
Q
lipid rafts
A
-involved in functions as diverse as assembly of signaling molecule, involvement in membrane protein trafficking, regulating neuro transmission and receptor trafficking
11
Q
flippases
A
- required for flipping of PL and SM against concentration gradient
- flopping down gradient requires scramblases or floppases
12
Q
lung surfactant
A
-dipalitoylphosphatidylcholine (DPPC) is PC with C1 and C2 esterified with palmitate
-produced and secreted from type II pneumocytes
-major component of surfactant
-other components are PG, apoproteins, SP-A, B, C and cholesterol
-lung surfactant resudes the surface tension of the alveoli of the lung and prevents their collapse
-deficiency in the synthesis of the components of lung surfactant leads to respiratory distress syndrome
(reduces pressure needed to fill them and prevents their collapse)
13
Q
PIP2
A
second pathway
- inositol added to CMP-DAG
- can go to PIP2
- then enriched in cytosolic leaflet
14
Q
phospholipase A2
A
- present in many mammalian tissues and pancreatic juice, snake and bee venom
- pancreatic secretions rich in proenzyme, activated by trypsin and requires bile salts for activity
- acting on PI, releases arachidonic acid
- inhibited by glucocorticoids
- cleaves at C1 and C2
- leaves lysophospholipids
- -can remove FA chains from membrane associated phospholipids
- chains can then be replaced with new ones by FA coa transferase
- surfactant is enriched this way
- also why carbon 2 of PI is associated with arachionic acid
15
Q
phospholipase A1
A
- present in many mammalian tissues
- cleaves at C1 and 2
- leaves lysophospholipids
- can remove FA chains from membrane associated phospholipids
- chains can then be replaced with new ones by FA coa transferase
- surfactant is enriched this way
- also why carbon 2 of PI is associated with arachionic acid
16
Q
phospholipase D
A
- involved in signal transduction
- generating PA from PC and DAG from PA
- cleaves off head groups
17
Q
phospholipase C
A
- found in liver lysosomes and a toxin of clostridia and other bacilli
- membrane bound is activated by the PIP2 system and plays second messenger roll
- cleaves head and yields DAG
18
Q
cell signalling
A
- PI has stearic acid associated with C1 and arachidonic on C2
- reservoir for arachidonic acid which can be released by A2
- phosphorylation of PI makes PIP2
- cleavage of membrane associated PIP2 occurs after hormones activate phospholipase C
- products of PIP2 cleavage are DAG and IP3
- IP3 stimulates release of calcium and DAG stimulates PKC
19
Q
sphingolidioses
A
- glycosphingolipids are internalized by endocytosis, which fuse with lysosomes that have hydrolytic enzymes
- specific lysosomal enzymes cleave specific glycosidic bonds-last on first off
- defects in cleavage lead to accumulation of the substrate in lysosomal storage diseases
- in normal cells, syn and deg is balanced
- when specific hydrolase is missing, one lipid accumulates
- caused by defects or diminishment of enzymes, diseases are called sphingolipidoses
- neurologic problems and premature death
20
Q
diagnosis
A
- enzyme assats in cultured fibroblasts or peripheral leukocytes
- histological examination of affected tissue
- and/or analysis of DNA
- gaucher, tay sachs, and niemann pick so high freq in Ashkenazi jewish pop
21
Q
Tay Sach’s disease
A
- problem with B-hexosaminidase A
- accumulation of gangliosides (GM2)
- rapid, progressive and fatal neurodegeneration
- blindness
- cherry red macula
- muscular weakness
- seizures
- deficiency in activator protein in some cases
22
Q
gaucher disease
A
- problem with B-glucosidase
- accumulation of glucosecerbrosides
- most common lysosomal storage disease
- hepatosplenomegaly
- osteoporosis of long bones
- CNS involvement in rare infantile and juvenile forms
- enzyme replacement therapy
23
Q
metachromatic leukodystrophy
A
- problem with arylsulfatase A (trying to get to ceraminde)
- build up of sulfatide
- cognitive deterioration
- demyelination
- progressive paralysis and dementia in infantile form
- nerves stain yellow/brown with cresyl violet
- deficiency of saposin B activator protein in some cases
24
Q
Krabbe Disease
A
- globoid cell leukodystrophy
- problem with B-galactosidase
- accumulation of galactocerebrosides trying to get to a ceramide
- mental and motor deterioration
- blindness and deafness
- near total loss of myelin
- globoid bodies in which matter of brain (glycolipid laden macrophages)
25
GM1 gangliosidosis
- problem with B galactosidase
- on the way down
- build up of GM1 gangliosides and keratan sulfate
- neuro deterioration
- hepatosplenomegaly
- skeletal deformities
- cherry red macula in infantile form
26
sandhoff disease
- problem with B-hexosaminidase
- accumulation of GM2 and globosides
- same neuro sx as tay sachs but visceral involvement as well
27
Fabry disease
- X linked
- problem with a-galactosidase
- accumulation of globosides
- red purple skin rash
- kidney and heart failure
- burning pain in lower extremities
- enzyme replacement therapy
28
Niemann-Pick disease
- problem with sphingomyelinase
- accumulation of sphingomyelin
- hepatosplenomegaly
- neurodegenerative course in type A
- cherry red macula
29
Farber disease
- problem with ceraminidase
- accumulation of ceramid
- painful and progressive joint deformity
- subQ nodules of lipid laden cells
- hoarse cry
- tissues show granulomas
