Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
98 Cards in this Set
- Front
- Back
|
What is cell biology? |
The study of the structures that make up a cell, how these structures function, form, and are maintained. |
|
|
How are structures built? |
Protein localization Membrane trafficking Cytoskeleton |
|
|
How are structures coordinated to drive cell function and cell behaviors? |
Cell cycle Cell adhesion Cancer |
|
|
Eukaryotic cells are compartmentalized... so that? |
A way to optimize cell behaviors and chemical reactions -concentrate and isolate reactants -optimize environment for reactions |
|
|
What is compartmentalization? |
A cellular compartment is usually a membrane encapsulated structure |
|
|
How did compartmentalization arise |
Plasma membrane grows around and engulfs an object
-Generation of nucleus and ER -Generation of mitochondria |
|
|
Compartmentalization meant that proteins must be targeted to a specific location... what are the routing possibilities? |
1)Cytoplasm 2)Nucleus 3)Mitochondria 4)Endoplasmic Reticulum |
|
|
What are sorting signals? |
-Amino acid sequences within proteins that direct protein localization and transport
-Oligosaccharides attached to amino acids |
|
|
How do we identify what the signal sequence is for a given protein?
|
1) Molecular biology approach: Take bits of transported protein and fuse or "clone" amino acid sequence to a reporter protein and check distribution (Classic reporter gene- GFP)
2) Biochemical approach: Direct purification of signal sequence
3) Genetic approach: Break (mutate) specific parts of protein to identify sequence for localization. |
|
|
Proteins can ________ _________ to correct location in cell, or be _________ within the cell |
Passively diffuse
Transported |
|
|
Protein transport may involve |
Gated transport
Translocator-based transport
Vesicular transport |
|
|
Gated Transport |
Controlled opening of pore complexes
Cytosol <--> Nucleus |
|
|
Translocator-based Transport |
Transmembrane protein translocator transfer protein from one side of the membrane to another. Protein must be unfolded to pass through.
Cytosol <--> Mitchondria, ER, Plastids, Peroxisomes
|
|
|
Vesicular Transport |
Often small spherical membrane packages that ferry proteins from one compartment to another
ER <--> Late endosome (lysosome), early endosome, secretory vesicles, cell exterior
Requires: -Selection of cargo -Fomation of a vesicle (budding) -Fusion of a vesicle with a target compartment |
|
|
Translocator-based Transport in the Mitchondrial Matrix |
-A few proteins made in mitochondria as directed by mitochondria DNA -Most imported from cytosol post-traslationally
-Most outer membrane (non-N terminal) signal that is not cleaved. -Most proteins destined for the matrix space have a cleavable N-terminal signal sequence
-Matrix signal usually an amphipathic alpha-helix
-Requires transporter complexes (TIM&TOM), protein chaperones (Hsp70), and energy (ATP&membrane potential)
1a. Cytosolic Hsp70 chaperones keep protein unfolded 1b. Signal sequence is bound by TOM complex 1c. Translocation and chaperone displacement begins through an ATP-dependent process
2a. Transport across outer membrane and inner membrane is coordinated, (transport of initial portion of matrix protein is not ATP dependent, matrix signal sequence is amphipathic and positively charged which uses the membrane potential to initiate crossing inner membrane)
3a. Signal sequence is removed by mitochondria protease 3b. mitochondrial Hsp70 chaperones bind matrix protein as it emerges ensuring directionality of transport after signal sequence cleavage 3c. Hsp70 chaperones displaced and matrix protein is allowed to fold and function through an ATP-dependent process |
|
|
Electron Microscopy |
1931 Electron wavelength ~100,000 (smaller than visible light) Cells stained with osmium and imaged with electron microscope
|
|
|
Endoplasmic Reticulum |
Comprises a network of membrane that penetrates much of the cytoplasm (~50% total membrane)
Highly dynamic
ER and nuclear envelope are contiguous
Two sub compartments (rough vs smooth) |
|
|
Smooth ER |
Short tubules
Functions: -Ca2+ storage -production of lipids, phospholipids, and steroids (Leydig cells) -detoxifying enzymes
Varies greatly in size in different cell types
Can expand when needed |
|
|
Extracellular |
Outside the cell |
|
|
Cytoplasmic |
the organized complex of inorganic and organic substances external to the nuclear membrane of a cell and including the cytosol and membrane-bound organelles (as mitochondria or chloroplasts)
Inside the cell |
|
|
Lumenal/ Cisternal |
Inside the membrane |
|
|
Rough ER |
Rough appearance due to the presence of ribosomes
Flattened stacks
Composition of the luminal/ cisternal space is different from the surrounding cytosolic space
Cytoplasmic entry point for proteins into vesicular trafficking system called biosynthetic pathway
Protein synthesis on membrane bound ribosomes vs free ribosomes
Protein modifications |
|
|
Membrane-bound ribosomes vs free ribosomes |
No difference in the ribosomes
Site of protein synthesis determined by amino-acid sequence at N-terminus of protein |
|
|
Protein Translocation into ER |
1. Signal sequence recognized by SRP 2. SRP binds to receptor/ translation stopped 3. Polypeptide moves into ER lumen through a protein lined pore 4. Movement can occur co-translationally or post-translationally
More specifically: 1. SRP RNA wraps around rRNA/ proteins of ribosomes and pauses translation 2. Attachment of ribosomes to ER membrane through the binding of SRP to the SRP receptor 3. Binding of SRP to protein translocator, triggering GTPase activity, and subsequent release of SRP. Translation resumes, seal is tight between ribosome and translocator 4. Cleavage of sequence signal 5. Protein inserted in ER lumen
Main components: 1)SRP 2)SRP Receptor 3)Translocon 4)Signal Peptidase
|
|
|
Signal Recognition Particle |
Made of 6 proteins and 1 RNA
Binds to signal sequences
Possesses a critical GTPase protein |
|
|
GTPase |
Active GTP-bound and inactive GDP-bound states |
|
|
Classical model in protein translocation in ER |
SRP dependent
Co-translational translocation |
|
|
Non-classical model in protein translocation in ER |
SRP independent
Post-translational translocation |
|
|
Integral Membrane Proteins |
Transmembrane proteins can have different orientations |
|
|
Translocaiton of luminal/ soluble protein |
Signal sequence is recognized twice (by SRP and by translocator)
Signal sequence is 6-12 hydrophobic amino acids
Translocator is gated in 2 directions, cytoplasmic and sideways bilayer opening |
|
|
Start and stop transfer sequences direct transmembrane proteins topologies |
Start transfer sequences (2 types)
Stop transfer signal
|
|
|
Start transfer sequences |
N-terminal signal sequence: a cluster of 8 hydrophobic amino acids at the N-terminal end of a protein. This sequence remains in the membrane and is cleaved off of the protein after transfer through the membrane
Internal start transfer sequence: Similar to a signal sequence, but is located internally (not at N-terminal). It also binds to the SRP and initiates transfer. Unlike the N-terminal signal sequence, it is not cleaved after transfer of the protein |
|
|
Stop transfer signal |
This is also a sequence of 8 hydrophobic amino acid residues. It follows either a N-terminal signal sequence or a start transfer sequence. The stop transfer signal is a membrane crossing domain. It remains in the membrane. The peptide is not cleaved. |
|
|
Protein modification in the ER |
Lipidation
Hydroxylation of amino acids (collagen)
Disulfide bond formation
Glycosylation |
|
|
Lipidation |
Addition of lipid to a protein
(ex: GPI-anchoring) |
|
|
Hydroxlyation of amino acids |
Addition of hydroxide (-OH) between between sulfur groups in cysteine amino acids |
|
|
Disulfide Bond Formation |
Intramolecular covalent bond between sulfur groups in cysteine amino acids
Oxydation reaction
Happens in the ER lumen but not in the cytosol: oxidizing environment
Protein disulfide isomerase |
|
|
Glycosylation (N-linked) |
Addition of carbohydrate (sugar) to a protein
Occurs in ER and Golgi
Starts in ER (14 sugar oligosacchride is covalently bonded, then transferred to Asparagine side chain, therefore yielding N-linked name)
Continues to Golgi
14 sugar consists of (Addition of glycans to a carrier): -2 N-acetylglucosamine -9 mannose -3 glucose
Transfer to protein
Sugars added to lipid carrier (dolichol phosphate)
Oligosaccharyl transferase: -mediates transfer -integral membrane protein with active site on -lumenal side -one copy of enzyme per ER translocator
Co-translational, within (N-X-S/T) sequence
Sugar transferred from dolichol lipid moiety
Energy for reaction comes from breaking pyrophosphate bond
Absence of N-glycosylation = embryonic lethal
Partial disruption of ER glycoslation = CDG -Diseases
|
|
|
Protein folding |
Unstructured chain of amino acid (inactive)
3D folded structure (active)
-all the information is needed for the folding is contained in amino acids sequence -amino acids have different properties (charge, hydrophobicity) -amino acids pack in such a way that the free energy of the protein arrives at a minimum
-glycolylation state -chaperone proteins -lumen environment
|
|
|
Protein quality control |
Protein folding is reflected in glycolsylation state: -two glucose removed -remaining glucose binds to calnexin (chaperone), retains proteins in the ER, gives time to hold -glucosidase removes glucose, releases proteins -If protein is folded, it can leave ER, if not, conformation sensing enzyme (glucosyl transferase) binds to misfiled protein and adds a glucose back
Proteins that are not folded correctly are exported back to the cytoplasm and are degraded
A slow acting mannosidase enzyme that trims a mannose off the oligosacchride tells the cell how long a protein has been in the ER
Mannose-clipped protein can no longer be recycled and instead is sentenced to degradation
Protein is exported from ER to cytoplasm
Presence of N-glycosylation indicates to the cytoplasmic degradation machinery that the protein should be degraded
Glucosyl transferase is fastest enzyme, then export machinery, and finally mannosidase is the slowest
The relative rates of the enzymes are key for the system to work |
|
|
Unfolded Protein Response (UPR) |
Under certain conditions, cell accumulates high levels of unfolded proteins in the ER
Emergency action plan= UPR -decrease translation -Increase ER -Increase in number of chaperones
If UPR is not sufficient, cell will trigger apoptosis |
|
|
Vesicular Transport |
Once a protein is folded, where does it go? |
|
|
Membrane trafficking |
Most require a vesicle
Exocytosis Endocytosis
Must be balanced |
|
|
Exocytosis |
The trafficking of lipids, proteins, and other compounds to the cell surface/ outside
|
|
|
Endocytosis |
The uptake of lipids, proteins, and other compounds front the cell surface/ outside |
|
|
Steps in vesicle transport |
1) Vesicle formation a. Cargo recruitment b. Budding 2) Vesicle scission 3) Transport and targeting 4) Tethering 5) Fusion |
|
|
Vesicle Formation |
Cargo Recruitment/ Budding
Adaptor proteins bind cargo receptors/ integral membrane proteins Adaptor proteins also recruit coat proteins
1) Cargo receptors bind specific proteins to be trafficked 2)Adaptor proteins bind cargo receptors/ integral membrane proteins 3) Adaptor protein binding concentrates cargo receptors, and thus recruits cargo to new bud 4) Adaptor protein recruit coat proteins to induce membrane curvature |
|
|
Three major types of vesicles |
Clathrin-coated
COP1-coated
COP2-coated |
|
|
Clathrin-coated vesicles |
dedicated to trafficking from golgi complex, plasma membrane, and some endosomal compartments |
|
|
COP1-coated vesicles |
dedicated to trafficking at the golgi complex |
|
|
COP2-coated vesicles |
dedicated to trafficking from the ER |
|
|
Clathrin |
Composed of heavy and light chains
Stable basic unit is a triskelion (3 heavy and 3 light)
Triskelions then function as the basic unit for higher order clathrin assembly (cage/ lattice)
Coat properly- reversible self-assembly
Drives vesicle formation |
|
|
Vesicle Scission |
Clathrin basket assembly cannot sever the lipid bilayer
Dynamin is recruited to bud neck
Dynamin cuts the bud necks to free the vesicle (costs energy- GTPase) |
|
|
G proteins can regulate coat formation and disassembly |
Arf1 (GTPase) protein regulate Clathrin and COP1 assembly
Sar1 (GTPase) regulates COP2 assembly
Cargo receptor proteins function as a (GAP or GEF) for Sar1 and Arf1
Sar1-GTP extends amphipathic helix
Assists recruitment of adaptor and coat proteins
BUT GTPases can function as timers regulating the duration of a coated vesicle
Eventually Sar1 and Arf1 proteins will hydrolyze GTP, return to inactive state, pull in the amphipathic helix, and the coat and adaptor proteins will fall off the vesicle |
|
|
Transport and targeting in Vesicle Transport |
Rab proteins act as address labels for vesicles -another class of GTPase protein -GTP binding causes amphipathic helix to become accesible -More than 60 known Rabs, different Rab proteins target different organelles -Rab proteins bind: -Motor proteins, mediate movement in cell -Tethering proteins, act to localize vesicle near target compartment |
|
|
Vesicle Tethering in Vesicle Transport |
Tethering proteins are bound to target compartment -recognize incoming vesicle -assemble into long, multi-protein complexes that reach into cytoplasm -bind to Rab and localize vesicle near target membrane |
|
|
Vesicle Fusion in Vesicle Transport |
SNARE proteins fuse lipid bilayers (zipper) -v-SNAREs (vesicle) and t-SNAREs (target) -1 v-SNARE and 3 t-SNAREs zip together to form 4-helix bundle -bundle formation drives bilayer apposition and water displacement
1)zipping 2)hemifusion 3)fusion pore |
|
|
What is GTP and GDP? |
GTP: Guanosine 5'-triphosphate -GTP hydrolysis
GDP: Guanosine 5'-diphosphate |
|
|
ER to golgi transport |
Vesicular tubular clusters are an important intermediate in ER to golgi trafficking -vesicles are transported toward golgi -as vesicles approach golgi, they begin to fuse together- homotypic fusion (ERGIC)
There must be sorting signals (or exit signals) on all proteins that will be recognized for transport out of the ER -lumenal cargo protein, transmembrane cargo protein, cargo receptor -adaptors and COP2 coat recruited |
|
|
How do you maintain composition of given compartment in ER to golgi transport? |
Retention and retrieval systems |
|
|
Retention system |
Mostly based on physical properties of proteins prevent them from entering transport vesicles (too large, short transmembrane domain)
Some proteins escape |
|
|
Retrieval system |
Can operate in both the VTC and Golgi
ER proteins have a sorting (or retrieval) signal that will signal whether the proteins should be kept of returned to the ER
ER resident membrane proteins will have a retrieval signal (KKXX) at C-terminus -this signal has a simple function and can directly bind to and recruit COP1 coat proteins
ER resident soluble proteins have a different retrieval signal (KDEL) at C-terminus
|
|
|
KDEL |
Cannot bind to COP1 directly
KDEL receptor (membrane protein)
KDEL receptor binds directly to COP1 coat proteins
KDEL receptor must function differently between ER and VTC/golgi -must not bind KDEL proteins in ER and must release proteins when it returns them to the ER -must bind KDEL proteins for retrieval in VTC/golgi
How?
-ER has neutral pH, golgi has proton pumps that make for a more acidic environment -KDEL is a pH sensative receptor (not active in neutral environment so is inactive in ER, releasing proteins and not re-binding them) |
|
|
Golgi Complex |
Stacked structure, flattened, dislike cisternae
Has cis (face), medial, trans (face)
Cis face is where proteins enter Trans face is where proteins exit to many different destinations in the cell
two key functions: 1)protein post-translational modification 2)protein sorting
|
|
|
Protein modifications in the golgi |
Phosphorylation (add phosphate) Glycosylation (N and O-linked) Sulfation (add sulfate) |
|
|
N-Linked Glycosylation in the golgi |
WHy? 1)can target proteins to specific compartment (lysosome) 2)Glycosylation introduces special structural qualities to proteins -sugars are some of the most rigid macromolecules -adding sugars will fend other proteins off as well as other organisms (protection) -Keeps protein from being attack by protease -keeps bacteria from approaching cell surface -a class of heavily glycosylated proteins are proteoglycans (hyaluronic acid/ mucins) |
|
|
Vesicular Transport Model |
Vesicles transport proteins through a golgi from distinct cisternal compartments |
|
|
Cisternal Maturation Model |
Entire cisternae slowly transit through golgi carrying the same cargo proteins throughout, must mature from a -cis functioning cisternae to a -trans functioning cisternae, likely through vesicular transport of golgi enzymes |
|
|
trans golgi network |
Sorting station for: -late endosome/lysosome -early endosome/recycling endosome -plasma membrane/ secretion (constitutive vs regulated)
Vesicles/ tubular carriers
Protein routing depends on -lumenal interactions -cystolic trafficking sequence |
|
|
exocytosis |
process by which materials get outside the cells or at the plasma membrane
Fusion pore, connection between outside and lumen of vesicle
Soluble proteins, membrane proteins, lipids
Organelles undergoing exocytosis: -late endosome/ lysosome -constitutive secretory vesicles -regulated secretory vesicles -secretory granules -synaptic vesicles |
|
|
What happens to a protein that has no sorting signal other that ER signal sequence and ER exit signal? |
Constitutive exocytosis is the default pathway (secreted or plasma membrane) |
|
|
Regulated vs Constitutive Secretory Pathway |
signal or no signal |
|
|
Secretory granules/ large dense core vesicles |
Different tissues/ cell types (endocrine, exocrine, neuronal)
Different sizes and content (insulin granules, zymogen granules)
Granulogenic proteins-tendency to aggregate TGN environment (pH, redox) Coat?
Undergoes homotypic fusion in maturation |
|
|
regulated exocytosis |
secretory vesicles localize to cell periphery but fusion is regulated -travel to PM after being made -prime for fusion (SNAREs) -fuse and release on signal (entry of Ca ions)
Complexin: acts as a clamp, prevents fusion Synaptotagmin:Ca sensor binding of Ca to synaptotagmin releases complexin (clamp)
Can view with electron microscopy (static is a problem) or with light microscopy (live imaging of fluorescent labelled proteins, Total internal reflection fluorescent (TIRF) microscopy allows to look at thin region
Two types: -full -kiss and run -kiss and stay (new)
Neurotransmitters, neuropeptides, peptide hormoes, growth hormones,
also can expand cell surface area. |
|
|
Synaptic vesicles |
mediate release of neurotransmitters at synapse
Major proteins: -vSNARE -synaptotagmin (Ca sensor) -vATPase (pH) -transporter(neurotransmitter)
Form locally, from endocytic vesicles
Mechanisms of regulated exocytosis very similar to secretory granules
|
|
|
Endocytosis |
The process by which materials get inside the cell
Constitutive and regulated |
|
|
Endocytic pathways permit |
-Nutrient uptake -Maintenance of cell membranes -Regulation of cell signaling -Hijacked by pathogens |
|
|
Main endocytic pathways |
Phagocytosis
Pinocytosis |
|
|
Phagocytosis |
Cell eating |
|
|
Pinocytosis |
Bulk-phase endocytosis (cell drinking) -Macropinocytosis -Receptor-mediated endocytosis |
|
|
Macropinocytosis |
-Engulfment large gulps of membranes -Irregular shape -Actin-dependent process initiated from surface membrane ruffles -General property of most cells, triggered by growth factors -Exploited by various pathogens (HIV, Vaccina, HSV, adeno 3) |
|
|
3 types of membrane ruffles |
Lamelliphdoia-like
Circular
Blebs |
|
|
Receptor-mediated endocytosis |
Way to internalize specific molecules/ selective uptake of extracellular molecules
1) Clathrin-mediated endocytosis 2) Caveolae-mediated endocytosis 3) Caveolin-independent-Clathrin-independent pathways
-Receptor binds to specific cargo -Receptor binds to adaptor -Adaptor interacts with coat protein -Constitutive vs ligand-induced internalization (housekeeping vs signaling) |
|
|
Clathrin-mediated endocytosis |
Form rapidly (1min to make coated pit) Thousands of clathrin coated vesicles leaving cell surface every minute Size of clathrin-coated vesicle 35-100nm Scission through dynamic |
|
|
Caveolae-mediated endocytosis |
Elongated flask-shaped structure in plasma membrane (50-80nm)
"little cave"
Composed of distinct proteins and lipids -caveolins and cavins (coat), GPI-anchored proteins (cargoes) -lipid rafts (cholesterol, spingolipids)
Unusual lipid composition (lipid rafts) believed to recruit cargo, not cargo receptors
Scission through function of dynamin
Abundant in endothelial cells, adipocytes, muscle cells -signal transduction, lipid regulation, mechanosensing |
|
|
F-actin-dependent endocytosis |
Polymerization of F-actin drives elongation and scission of invaginated membrane |
|
|
Receptor-mediated constitutive endocytosis |
LDL=low density lipoprotein, transports cholesterol in blood (from liver to body cells)
cholesterol esterified to long-chain fatty acids
-single layer of phospholipid -single copy of apolipoprotein B100
Apolipoprotein B-100 binds to LDL-R
Level of LDL in blood related to development of artherosclerosis
LDL receptor taken up whether cargo bound or not/ constitutive cycling |
|
|
Ligand-induced internalization |
Receptor tyrosine kinases (EGF receptor) Many GCPR (beta2-adrenergic)
Endocytosis can regulate signaling by controlling number of receptor at plasma membrane
Mostly clathrin-dependent endocytosis
RTK/ GPCR Some mutations in EGF R associated with cancer, affect trafficking |
|
|
Endosome |
Membrane bound organelle
Different types: -early endosome -recycling endosome -multivesicular bodies/ late endosome -endolysosome--lysosome
Characterized: -by particular protein, lipid content, and pH -by the time it takes for endocytosed material to reach it -by different morphology
Can represent same organelle at different stage of its life
Acts as a sorting station for internalized proteins and lipids -plasma membrane directly (fast) or through recycling endosome (slow) -lysosome (degradation) -TGN (retrograde transport) |
|
|
Early endosome |
Usually near periphery First organelle visited by endocytic vesicles
Characteristics: -Rab5 -PI3P (phosphatidylinositol 3 phosphate) -tubules -pH ~6-6.5
|
|
|
Endosomal Recycling Compartment (ERC) |
Glucose transporter (GLut4) stored in specialized recycling endosomes in adipocytes and muscle cells
Can be mobilized when needed (insulin signaling)
Recycling and Transcytosis -Proteins can be recycled from endosomal compartments -Early endosomes are not actively digesting compartments -pH not acidic enough for many acid hydrolyses to function -Proteins can be shuffled from one cell surface to another through a combined process of endocytosis and exocytosis (transcytosis) |
|
|
Late endosome/ multi vesicular bodies |
Transition/ maturation from early endosome to lysosome
-Homotypic fusion of early endosome, increase in size -Budding of intraluminal vesicles -Change in protein composition/ Rab5 to Rab7 transition -Decrease in pH (4.5-5.5) -Lack of tubules
Same process used by HIV, Influenza, and Ebola to bud from cells
DEPEND ON ESCRT PROTEINS
Monoubiquitination used to label transmembrane proteins for degradation |
|
|
Lysosome |
Site of intracellular digestion Heterogeneous (different size, shape) Found in al mammalian cells, except red blood cells Receive inputs from both biosynthetic and endocytic pathways
Mechanisms of macromolecule degradation The lysosome and the proteasesome, the garbage disposals of the cell -proteasome only degrades proteins, diffuses freely within cytoplasm -lysosome can degrade many types of macromolecules
Pathways to the lysosome: input from biosynthetic pathway (hydrolyases) where is the "food" coming from? -endocytosis -phagocytosis -autophagy
Lysosomes have a variety of acid hydrolases -proteases, nucleases, glycosidases, lipases, phospholipases, phosphatases, sulfatases
these enzymes give the lysosome the ability to break down almost any macromolecule -lysosomes break down targeted intracellular structures, extracellular debris, phagocytksed cells/ bacteria/ viruses, nutrients for cell
breakdown of macromolecules produced new nutrients
Acid hydrolyses require an acidic environment to function, which protects the cell -vacuolar H+ (proton) pump uses ATP to drive protons into lysosome -acid hydrolyses are highly glycosylated
Hydolases mediate digestion, how do they get there? -Targeting motif -mannose 6-phosphate (M6P) -added in cis-Golgi by GIcNAc phosphotransferase |
|
|
Lysosomal Phosphatases |
-sugar serves as a marker for protein trafficking -M6P serves as a lysosomal cue -When lysosomal signal sequence is present on a protein, a P-GIcNAc is added to M6P on N-linked oligosaccharide -GIcNAc then chopped off leaving M6P -M6P receptor in TGN binds M6P and clathrin adaptor proteins -Acid hydolases not active until arrival in highly acidic lysosome
ESSENTIAL ROLE OF PH |
|
|
What happens of hydrolyses can get to the lysosome? |
lysosomal storage disease
Defect in GIcNAc phosphotransferase, undigested substrate accumulate in lysosome of fibrolast |
|
|
Vacuoles |
Lysosome-related organelles
Can undergo regulated exocytosis
-Melanosomes -in melanocytes in epidermis, store pigment and release it -pigment taken up by keratinocytes, leading to skin pigmentation
-Weibel Palade Bodies -in endothelial cells, store von wile brand factor and P-selectin -role in blood coagulation and inflammation
-lytic granules |
|
|
Membrane lipids |
Amphipathic
Three main types of membrane lipids: 1) phospholipids (phosphoglycerides) -made of diglycerides and phosphate group 2)sphingolipids (less abundant) -sphigosine (amino acid) -ex:ceramide, sphingomylein -can be used to make glycolipids (cerebroside, ganglioside) -form lipid rafts with cholesterol 3)cholesterol -interferes with movement of fatty acid tails of phospholipids and tend to stiffen membranes -form lipid rafts with sphingolipids |
|
|
Phospholipids Biosynthesis |
Site of assembly- smooth ER Objective: Make phosphatylcholine
Gycerol phosphate + 2 fatty acid acyl-CoAs are linked by the enzymes Acyl Transferase. This reaction occurs on the Cytosol side of SER The product is phosphatidic Acid
Step 2: A phosphatase removes the phosphate the phosphatidic acid This product is a diacylglycerol
Step 3: CDP-Choline and Diacylglycerol in the presence of the enzyme Choline Phosphotransferase will make phosphatidylcholine
Step 4: Flippase will move some of the phosphartidylcholine tot he lumenal plane of the ER membrane |
