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MCP Unit 6 > Complex Lipids > Flashcards

Complex Lipids Flashcards

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
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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
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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
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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
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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
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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
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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
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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
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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
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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

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11
Q

flippases

A
  • required for flipping of PL and SM against concentration gradient
  • flopping down gradient requires scramblases or floppases
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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)

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13
Q

PIP2

A

second pathway

  • inositol added to CMP-DAG
  • can go to PIP2
  • then enriched in cytosolic leaflet
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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
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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
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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
  1. enzyme assats in cultured fibroblasts or peripheral leukocytes
  2. histological examination of affected tissue
  3. 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
Q

GM1 gangliosidosis

A
  • 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
Q

sandhoff disease

A
  • problem with B-hexosaminidase
  • accumulation of GM2 and globosides
  • same neuro sx as tay sachs but visceral involvement as well
27
Q

Fabry disease

A
  • 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
Q

Niemann-Pick disease

A
  • problem with sphingomyelinase
  • accumulation of sphingomyelin
  • hepatosplenomegaly
  • neurodegenerative course in type A
  • cherry red macula
29
Q

Farber disease

A
  • problem with ceraminidase
  • accumulation of ceramid
  • painful and progressive joint deformity
  • subQ nodules of lipid laden cells
  • hoarse cry
  • tissues show granulomas

MCP Unit 6 (9 decks)

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