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What percent of the total cell volume can be attributed to MEMBRANES?
50%
the plasma membrane accounts for 10% of the cell volume
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Membrane Chemical Composition: Take-home Message
most membranes are a little less than half protein, a little less than half lipid, & have a small amount of carbohydrate (this can vary greatly depending on the function of the membrane)
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Notable Membrane Compositions
- • Myelin: 79% lipid, 18% protein, 3% carbohydrate
- - proteins are amphoteric (can conduct electricity) but lipids can’t; good way to protect electrical impulses from going astray
- • Mitochondrial Inner Membrane: 76% protein, 24% lipid, <1% carbohydrate
- - ox.phos enzymes & ion exchange proteins are necessary for ox.phos to occur
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List the classes of membrane lipids in order of abundance in most membranes:
- 1. Phospholipids
- 2. Sphingolipids
- 3. Cholesterol
- 4. Eicosanoids
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How are lipids distributed in the membrane?
ASYMETRICALLY
this is important because the outer leaflet is generally much more fluid than the inner leaflet, allowing lipid rafts to rapidly concentrate ligand-receptor pairs at specific sites on the membrane for internalization
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Eicosanoids
made from the phospholipids in the plasma & make up a small, but important part of the plasma membrane; are precursors for major regulatory functions within the cell
3 classes = Prostaglandins, Leukotrienes, Thromboxanes
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Prostaglandins
induces uterine contractions (PGE2), carries out vasodilatation, platelet aggregation, vasoconstriction
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Thromboxanes
induce platelet aggregation (TXA2) & vasoconstriction
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Leukotrienes
- induce vasodilation & bronchoconstriction in asthma (LTC4, LTD4, LTE4) & are components of SRS-A [slow reacting substance of anaphylaxis, discovered in individuals suffering from anaphylaxis]
- • create problem of suffocation during anaphylaxis & an asthma attack
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Phospholipids
• provide the major structure for the plasma membrane
• have hydrophilic head + fatty acids that make up the hydrophilic interior of the PM (usually 16-18 Cs long)
• are capable of FUSING (energetically favorable process)
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What are the components of the phospholipid head?
1. Polar head groups (Choline)
2. Phosphate group
3. Glycerol group
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HIV & the Fusogenic Property of Phospholipids
• lipid membranes can rapidly & spontaneously fuse with one another (eg. lipid vesicles can fuse with membrane-bound organelles or with the PM)
• HIV has a viral coat protein that’s recognized by CD4 receptor on T-cells, macrophages, & other cell types
• when CD4 positive cells bind HIV, a rapid fusion of the viral coat lipids with the host cell membrane occurs
• this results in entry of the viral capsid & nucleoproteins into the host cell cytoplasm where replication of the viral genome ensues
• viral glycoprotein recognized by CD4 is inserted into the infected cell PM
• this infected cell can now fuse with other CD4 positive cells, even in the absence of external virus
• resulting multi-nucleated syncytium is incapable of rendering a proper immune response
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What two viruses utilize the fusogenic properties of phospholipids (aka cell membranes) to spread?
HIV
Measles [cells infected with measles can fuse with healthy cells resulting in the spread of the virus]
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What’s the do sphingolipids & phospholipids have in common & how do they differ?
they are structurally similar & perform similar functions in the plasma membrane, but sphingolipids DO NOT have fusogenic properties
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Sphingolipids
• made up of 2 straight chained FAs; they have no (cis) double bonds, are fully saturated
• also have different head groups than phospholipids
• 2nd most numerous type of membrane lipid in the PM after phospholipids
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What happens if the cell does not dispose of sphingolipids properly?
different types of lysosomal storage diseases result
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Diseases of Sphingolipid Metabolism
• each caused by a single enzyme defect
• to “fix” can either replace enzyme or break down whatever protein is being built up
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Tay-Sachs Disease
caused by a deficiency in Hexosaminidase A that disrupts sphingolipid breakdown resulting in buildup of GM2 ganglioside
causes mental retardation, blindness & early death
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Gaucher’s Disease
caused by a deficiency in Glucocerebrosidase
Glucocerebroside builds up
causes hepatosplenomegaly, mental retardation & long bone degeneration
can be treated with enzyme replacement therapy
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Fabry’s Disease
α-Galactosidase A deficiency results in ceramide build up in lysosomes
characteristics include a skin rash & kidney failure
can be treated with enzyme replacement therapy
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Niemann-Pick Disease
sphingomyelinase deficiency
sphingomyelin builds up
results in mental retardation, hepatosplenomegaly
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GM1 Gangliosidosis
GM1 Gangliosidase deficiency
GM1 ganglioside builds up
results in mental retardation, bone malformations, hepatomegaly
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Factors Affecting Membrane Fluidity
- 1. Double Bonds
- 2. Acyl Chain Length
- 3. Temperature
- 4. Cholesterol
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Double Bonds effect on Fluidity
• More double bonds: increased fluidity (kinkier)
• Fewer: decreased fluidity (more rigid)
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Acyl Chain Length effect on Fluidity
• Shorter: MORE fluid
• Longer: less fluid
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Temperature effect on Fluidity
• higher temp: more fluid
• lower temp: less fluid
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*Cholesterol effect on Fluidity*
• more cholesterol: LESS fluid
• less cholesterol: more fluid
just remember cholesterol has an inverse relationship with fluidity (the more C, the less fluid, the less C, the more fluid)
AT BODY TEMPERATURE
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Walking (Mycoplasma) Pneumonia
• mycoplasma bacteria enters the lungs & attaches to the base of respiratory cilia where it extracts cholesterol from the plasma membrane surrounding the cilia
• this causes the cilia membrane to become limp & incapable of beating, which results in mucous accumulation in the respiratory tract & provides a rich environment for mycoplasma to thrive
• secondary bacterial pneumonia often sets in with untreated mycoplasma pneumonia, as proper cilia function is an important part of the body’s ability to combat pathogenic organisms
• most common pneumonia in humans (+ pigs!)
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Lipid Rafts
specialized cholesterol & sphingolipid-rich microenvironments in the membrane that move rapidly in a leaflet
• are major functional organizers of the membrane, bringing lipids & proteins together
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What are lipid rafts critical for?
1. signal transduction
2. endocytosis
3. rapid re-organization of the membrane for extracellular matrix modification & motility
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How many amino acids (AAs) does it take to span a membrane?
~20-25
• AAs are almost all hydrophobic in the middle membrane-spanning segment
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Band 3 Protein
- • the anion exchanger in RBCs
- • has 14 membrane spanning sections
- • has oligosaccharides that can help it stick to the ECM
- • on the N-term site it has binding sites that anchor it
- • knows when to start exchanging anions
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What are 3 functions of carbohydrates on the cell surface?
- 1. blood-type antigens
- 2. pathogen recognition sites
- 3. reservoir for cytokines/growth factors
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Toxoplasmosis
- • toxoplasma is a pathogen found in cat feces that has the potential to cause severe birth defects in unborn children
- • protozoan binds to certain cells in the body based on the glycoproteins expressed on those cells
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Coccidiosis
coccidia recognize specific carbohydrates on the intestinal epithelial cell surface
• a major cause of very serious GI problems in countries that have issues with water/food supply
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