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Three Classes of Membrane Lipids in animal cells:
Phospholipids, Cholesterol (15%), Glycolipids (5%)
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Fatty Acid structure consists of...
head made of...
tail made of...
- Hydrophillic head- carboxyl croup
- Hydrophobic tail- Hydrocarbons
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Saturated vs. unsaturated (benefits...)
- ~saturated means there is no double bonds in the hydrocarbon tail, there is as many H atoms present as possible to allow free rotation.
- ~unsaturated means there is one or more double bonds present in the hydrocarbon tail, double bond creates a kink/rigidity, and also fewer H atoms.
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4 Major Phospholipids (including +/-/=, and which side of membrane it is)
5th phoshpolipid:
- 1) Phosphotidylethanolamine (+)
- 2) Phosphotidylserine (-) cytosolic side
- 3) Phosphoytidylcholine (=) cystolic side
- 4) sphingomyelin (=)
- 5)Phosphatidylinositol (located in the inner half of plasma membrane ONLY, small amounts- important in cell signaling/hormones)
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Glycolipid structure:
Carbohydrate, serine, carboxyllic tails
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glycolipids location and function
- exclusively found on the extracellular portion of bilayer
- form a carbohydrate coat (glycocalyx)
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glycocalyx
cell coat fromed from glycolipids to protect the cell from injury and create cell adhesion
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Cholersterol (function and location)
- provides cell membrane regidity
- large quantities in cell membrane (between hydrophobic tails)- very small in size
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Membrane fluidity:
- dynamic fluid like structures
- lateral movement
- rotational movement
- NO flip-flop (rare)
- shorter phospholipids provide more fluidity
- kinks give more fluidity (packed less effectively- more unsaturated= more fluid)
- more cholesterol= more rigid
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symmetry of membrane??
assymetrical due to the two faces of bilayer being very different (ex: glycolipids are extra cellular only!!!)
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Assymetry is important for function b/c:
- ~cytosolic proteins bind to specific phospholipid head groups
- ~cell death
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Membrane proteins:
- ~myelin membrane (electrical insulation of nerve axon <25%)
- ~mitochondrial membrane (ATP synthesis >75%)
- ~proteins can have carbohydrate chains attached (i.e. glycoproteins on glycolipids)
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3 ways proteins attach to membrane:
- 1) transmembrane (integral)
- 2) Lipid Linked (integral)
- 3) Protein linked (peripheral)
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Transmembrane Proteins:
Extend through the bilayer, consist of both hydrophobic and hydrophilic domains
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Lipid Linked Proteins:
Located entirely on the outside, covalently attached to lipid/glycolipids
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Protein Linked:
Bound indirectly to either face of the membrane by weak interactions (peripheral proten) (weak and break off readily)
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Function of Membrane Proteins:
- ~Transport (e.g. glucose transporter protein)
- ~Enzymes (e.g. adenylate cyclase- plasma membrane bound enzyme)
- ~Receptor (e.g. insulin receptor)
- ~Recognition (e.g. Cell-cell recognition, immune recognition)
- ~adhesion (e.g. cell adhesion proteins linkage to the ECM)
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movement of membrane proteins:
rotation diffusion and later diffusion- no flip flop
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Example of cells confining lipids and proteins to particular domains of the membrane:
- gut epithelium- membrane proteins restrict to particular omains of the plasma membrane
- apical membrane/gut lume has protein A exclusively to transport nutrients from the gut
- basal membrane has protein B exclusively to aid in transport to tissue/bloodstream
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Traffick across membranes:
- plasma membrane is a barrier to most hydrophilic molecules
- permeable to small non-polar molecules (O2 and CO2), and water molecules readily cross lipid bilayers
- impermeable to ions and charged molecules
- (~specialized transport systems are required to transport ions, sugars, aminoacids, nucleotides, etc.)
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Diffusion:
molecules to pass through the membrane directly (H2O, CO2)
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Facilitated transport:
- membrane proteins transport down a concentration gradient (e.g charged ions- Na+. Cl-)
- glucose transport in rbcs
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active transport:
- membrane proteins require energy (ATP)
- can transport up or down a concentration gradient (e.g. Na+/K+ pump)
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Endocytosis vs. exocytosis
- Endocytosis: invagination of membrane--> fusion of membrane to form vesicles (within the cell)
- Exocytosis: vesicles bud off ER or Golgi --> fusion of vesicle with membrane
(membrane will remodel)
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Cytosol: (4 facts)
- area outside organelles
- 50% of cell content
- metabolic processes take place
- contains cytoskeleton
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Cytoskeleton
(3 types of filament and function)
- Provides shape, cell movement, movement of organelles, mitosis
- ~Microtubules usded for division
- ~actin filaments for structure
- ~intermediate filaments for the inbetween stages
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Describe the structure of the cell!!!
Extracellular fluid, Cytoplasm, Glycoprotein, glycolipid, cholesterol, carbohydrates, peripheral proteins, integral proteins, etc.
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Major Organelles:
Nucleolus, nuclear membrane, mitochondria, ribosomes, smoothe Endoplasmic Reticulum, plasma membrane, golgi apparatus, golgi vessicle, rough ER, Lysosomes
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Protein Trafficking:
- Process of directing each newly made polypeptide to a particular destination
- most proteins are encoded by nuclear DNA (except mitochondrial DNA) and synthesized on ribosomes in the cytosol
- distributed to correct destination via action of sorting signals
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Signal Sequences:
- signal or sorting sequences direct delivery of proteins to specific organelles- if no sorting signal will remain in cytosol.
- receptor proteins on organelle surface recognize specific signal/sorting seq. in the new protein
- Must be a particular set of sequence to be transported/sorted/etc.
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Nucleus (4 facts):
- present in all cells in body except RBC
- contains DNA (site of mRNA synthesis)
- enclosed by two membranes with nuclear pores
- houses genetic material
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(sub-organelle) Nucleolus (2 facts)
- site of synthesis of ribosomal RNAs (rRNA)
- rRNA comples w/ proteins to form ribosomes
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Examples of Macromolecules traffick between nucleus and cytosol:
- RNA and DNA polymerases and histones go to nucleus send mRNAs and ribosomal proteins to cytosol which in return send RNA and DNA pol back to nucleus.
- (Nuclear localisation signal directs protein from the cytosol to the nucleus)
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Ribosomes (4 facts)
- site of protein synthesis
- large complex of proteins and ribosomal RNAs
- Eukaryotic ribosomes consist of 2 subunits (40s and 60s= 80s)
- can be bound or free
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Endoplasmic Reticulum (3 facts)
- Netweork of membrane enclosed tubules and sacs (cistemae) extend from nuclear membrane throughout the cytoplasm
- rough ER is covered by ribosomes on outer surface- site of protein synthesis
- smooth ER is not associated with ribosomes involed in lipid metabolism
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Proteins syntesised on Rough ER (KNOW THESE!!!!)
- Proteins destined for secretion (Hormones, digestive enzymes)
- Plasma membrane proteins (final destination- integral p)
- proteins destined for the golgi or lysosomes
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Proteins synthesised on free ribosomes
- destined for cytosol
- proteins destined for: nucleus, peroxisomes, mitochondria
- (glycolysis, anything not going to membrane)
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Steps to synthesis on Rough ER
- ALL protein start synthesis on free ribosomes
- if has ER signal sequence the ribosome attaches to ER
- as polypeptide chain grows it passes through the ER membrane into the lumen
- newly synthesised proteins accumulate in the lume or embedded in the ER membrane
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Rough ER Post translation Modifications (KNOW THESE)
- Formation of disulfide bonds (isuline)*
- Proper folding *
- Addition and processing of carbohydrates (glycocalyx)
- specific proteolytic cleavages (digestion)
- assembly into multimeric proteins*
- *occur exclusively in the RER
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Proper Folding (post translational modification)
- chaperone proteins direct the folding of proteins into their proper 3-D structure
- Needs energy
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Misfolded proteins:
if misfolded they are usually exported to cytoplasm and degraded
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Proteosome
A multiprotein protease complex where degradation takes place
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cystic fibrosis
caused by mutation in membrane protein, result in incorrect folding, and protein is retained in the ER
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function of the smooth ER
- detoxification of drugs/toxins
- synthesis of lipids and carbohydrates
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Golgi Apparatus (4 facts)
(proteins synthesised on the RER are further packaged in the Golgi apparatus)
- Membrane bound
- flattened stacks of smooth membranes or vesicles
- located close to the nucleus
- modifies/processes proteins and directs them to plasma membrane or internal organelles
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Export of proteins from the ER to the golgi complex
- p synthesised on RER exit in transport vesicles
- vesicles fuse with the cis-golgi comples
- p migrate through the golgi cisternae to the trans-golgi
- p are again packaged in vesicles
- w/in the golgi p undergo further modifications (add of carbohydrate groups, proteolytic cleavage)
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export from golgi to the plasma membrane
Exocytosis by vesicle budding and fusion
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summarize intracellular protein trafficking pathway:
RER--> Golgo--> Transport vessicles (may be directed to lysosoles next or)--> plasma membrane--> secretion
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Mitochondria
- Consists of 2 seperate membranes (inner and outer) and an inter membrane space
- inner membrane is highly convoluted- cisternae
- harness energy to produce ATP
- metabolic processes (oxidative phophorylation, electron transport)
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traffick proteins into mitochondria
- mitochondria have own DNA (30)
- most mito proteins are encoded by nuclear DNA (synthesised of free ribosomes)
- specific signal allows entry to mitochondria
- p are unfolded and transported across membrane (chaperone proteins assist to help and protein refold... required energy)
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Lysosomes
- membrane bound small vessicles
- degrade components of the cells
- contain degradative enzymes (nuclleases, proteases, phosphatases)
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traffick of proteins into lysomsomes (4 steps)
- synthesised in the ER
- thransported through golgi to the trans-golgi
- while in ER and cis-golgi the p become tagged (mannose 6 phosphate)
- allows recognition by appropriate receptor allows deliver to the lysosomes (mannose 6 phosphate receptor)
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Peroxisomes
- membrane bound small vesicles
- contain oxidases
- oxidise organic substances- generate highly toxic hydrogen peroxide (H2O2)
- traffic of proteins into peroxisisomes not well understood
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Summary of Intracellular protein trafficking pathways:
- rough ER-->Golgi-->transport vesicles-->lysosomes or plasma membrane-->secretion
- free ribosomes-->cytosol or nucleus or mitochondria
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