Reading...
Play button
Play button
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;
171 Cards in this Set
- Front
- Back
|
What about regulating gene expression to regulate enzymes?
|
This is relatively slow and wastes energy.
|
|
|
What is regulated proteolysis?
|
Degradation can be fast, but is not reversible
|
|
|
What about covalent modifications and enzyme regulation?
|
(phosphorylation is the most common)
This is fast and readily reversible Can cause major conformational change in protein, which alters function New phosphate group, in the context of surrounding amino acids, can form binding site for a new protein |
|
|
Feedback inhibition and enzyme regulation?
|
The product of a metabolic pathway inhibits an enzyme in the early steps of the pathway
Fast, specific and readily reversible Inhibition can be competitive with substrate at the active site or Non-competitive at a distal site (allosteric modulation) |
|
|
What about Controlling enzyme concentration to regulate enzymes?
|
Many enzymes are so fast that they are limited by access to substrate
==> “diffusion-limited” Rates can be increased by increasing substrate or enzyme concentration Multienzyme complexes – increase substrate availability Membrane-delimited compartments (subcellular compartments) |
|
|
What are the 3 major branches of life?
|
Bacteria, Archaea(Prokaryotes) and Eukaryotes
|
|
|
What are archea?
|
“extremophiles”
live at extremes of temperature, salinity or pH frequently have exotic metabolisms, membranes made of isoprenoids are not known to cause human disease |
|
|
What do bacteria and eukaryotes use for energy?
|
use fermentation, oxidation or photosynthesis for energy
|
|
|
The basics of ALL cells
|
All cells are solutions of proteins enclosed by a membrane
All cells use nucleic acids to store and transmit hereditary information All cells use energy |
|
|
How do Bacteria differ from Eukaryotes?
|
BACTERIA are haploid ==> more mutations will change phenotype
BACTERIA have more genetic flexibility, but also more dangerous BACTERIA lack internal compartments no nucleus ==> transcription and translation are coupled Bacterial ribosomes are slightly different from eukaryotic ones Bacteria have a cell wall to maintain cell structure, while eukaryotes have a cytoskeleton antibiotics exploit these differences in bacteria to kill them, while leaving eukaryotic hosts unharmed |
|
|
What are some basic functions of Lipids?
|
Form membranes
Store energy Can act as signaling molecules |
|
|
The basics of the lipid membrane and formation of selective barrier
|
With lipids forming the barrier and
proteins allowing communication across the membrane Both lipids and embedded proteins are free to diffuse laterally in the membrane forming what is sometimes called a “fluid mosaic” Lipid and protein composition varys with function 1.From membrane to membrane (plasma membrane vs. ER membrane) From cell type to cell type 2. Even with in areas of the same membrane ==> lipid rafts Composition of membranes is dynamic due to vesicular transport |
|
|
What are integral membrane proteins?
|
have one or more hydrophobic or amphipathic helices that pass through the membrane
these proteins are frequently specialized for communication ==> transporters, ion channels, signaling molecules |
|
|
What are peripheral proteins?
|
held to the membrane by electrostatic interactions with integral membrane proteins or phospholipid head groups
|
|
|
Lipid-anchored proteins are ...
|
covalently attached to a lipid in one leaflet of the membrane
GPI linkage (glycosylphosphotidylinositol glycan anchor) The prion protein is a GPI linked protein enriched in the outer leaflet of neurons |
|
|
What is purpose of membrane proteins being tethered to cytoskeleton?
|
to restrict mobility
coordinating protein localization allows molecules with specialized functions to work together ==> signal transduction |
|
|
What is structure and function of cytoskeleton?
|
Intracellular support network is a characteristic of eukaryotes
IMPORTANT for: 1. maintaining cell shape 2. establishing cell polarity (axons vs dendrites in neurons, budding in yeast) 3. cell movement (chemotaxis, cell migration during development) |
|
|
What are some basic of actin filaments?
|
(microfilaments)
1. form dense network underlying plasma membrane 2. important for cell shape and motility 3. substrate for myosin motor proteins important for muscle contraction very dynamic 4. G-actin bound to ATP assembles at the Plus end 5. ATP is slowly hydrolized to ADP this causes a conformational shift which favor depolymerization |
|
|
What is important about tubulin filaments?
|
(microtubules)
1.establishing cell polarity 2.positioning organelles 3.forming the spindle during mitosis 4.substrate for kinesin (toward the cell surface), dynein (toward the nucleus) motor protein==> substrate for most vesicle movement 5.VERY DYNAMIC a. βα-dimers bound to GTP associate with the Plus end b. GTP is gradually hydrolized to GDP which promotes dissociation |
|
|
What about Intermediate Filaments?
|
Composed of various different proteins
some are common to all cell types (nuclear lamins) others are specialized in different cell types: a. neurofilaments in neurons, b. cytokeratins in epithelia Give mechanical strength to cells |
|
|
________is the area enclosed by the plasma membrane
but excluding the nucleus and other organelles Approximately half of the total volume of the cell varies between cell types Major site of protein synthesis and degradation Major site of intermediary metabolism enzymes for glycolysis are in the cytosol Packed with macromolecules but small molecules diffuse nearly as fast as water |
Cytosol
|
|
|
pore is an aqueous pore
allows free diffusion of small molecules (< 5 kD) For larger molecules nuclear transport is an active process proteins transported folded Import requires a nuclear localization signal (short sequence of basic aa) |
Nucleus
|
|
|
Import and export receptors are
|
Importins moves along FG repeats that line the pore
Exportins mRNA must be properly spliced Ran GTPase binds to both import and export receptors provides directionality |
|
|
What are MicroRNA's?
|
small, endogenous, non-coding RNAs, transcribed just like mRNA or tRNA
Single-stranded transcripts fold into imperfectly base-paired hairpin structures Cleaved in cytoplasm into ~25 nt products these hybridize to specific sequences in mRNA targets ==> block translation or result in message degradation of specific targets ~ |
|
|
___________are synthetic molecules designed to exploit the miRNA mechanism
to decrease or abolish the expression of a target protein |
Short hairpin RNAs (shRNA)
|
|
|
How many known mRNA genes?
|
400 human miRNA genes known
may represent 2 – 3% of all genes |
|
|
What are some of roles of mRNA?
|
Play a role in translational inhibition, RNA stability, and the formation of heterochromatin
|
|
|
What is mitochondria composed of?
|
outer membrane, inner membrane, intermembrane space, matrix
|
|
|
has a transport protein that has a large aqueous channelpasses small molecules freely (< 5kD)
|
Outer membrane
|
|
|
has enzymes for oxidative phosphorylation
generates most of cells ATP many infoldings, called cristae, to increase surface area specialized lipids make it highly impermeable must hold the H+ gradient for ATP synthesis |
Inner membrane
|
|
|
____________has enzymes of the tricarboxylic acid cycle, and for pyruvate and fatty acid oxidation
contains mtDNA, ribosomes, etc. genome inherited maternally (sperm contribute little cytoplas disease causing mutations effect tissues with high energy requirements ==> skeletal muscle, neuronal tissue |
Matrix of mitochondria
|
|
|
Proteins synthesized on ribosomes in the cytosol are destined for:
|
cytosol, nucleus, mitochondria or peroxisomes
|
|
|
Proteins synthesized on the endoplasmic reticulum are:
|
Integral membrane proteins
Secreted proteins Lysosomal proteins |
|
|
Proteins are targeted to specific destinations by_______________.
|
sorting signals
|
|
|
What are signals?
|
These are brief stretches of aa's that are recognized by complimentary sorting receptors
The signal can be linear in the primary aa sequence or aas from different regions can form a patch on the cell surface after the protein folding |
|
|
What are some examples of sorting signals?
|
1.nuclear localization sequence (~5 basic aa)
2.signal sequence for ER (8 or more non-polar aa) 3.mannose-6-P for lysosome targeting 4. ER retention or exit signals |
|
|
“inside” intracellular transport
|
cytosol, nucleoplasm
|
|
|
“outside” intracellular transport
|
ER, Golgi, transport vesicles, lysosomes
|
|
|
What are three types of intracelluclar transport?
|
gated, transmembrane, vesticular
|
|
|
cytosol ↔ nucleus (topologically equivalent compartments)
aqueous pore, proteins do not need to unfold |
gated transport
|
|
|
cytosol ↔ ER (topologically distinct compartments)
cytosol ↔ mitochondriaproteins need to unfold |
Transmembrane transport
|
|
|
ER ↔ Golgi ↔ plasma membrane (topologically equivalent)
membrane enclosed, proteins do not need to unfold vesicles bud off one organelle and fuse with the next both membrane components and the aqueous contents are delivered |
Vesicular transport
|
|
|
budding off of the plasma membrane is known as _____________.
|
endocytosis
|
|
|
________requires fusing with the plasma membrane and results in release of material
|
exocytosis
|
|
|
In exocytosis and endocytosis.....
|
vesicles are coated with proteins as they bud off (clathrin, COPI, COPII)
the proteins structurally aid the budding process, but then are shed ==> not involved in targeting the vesicles |
|
|
Everything you need to know about Rab proteins...
|
target vesicles (over 60 known family members)
Rab proteins are monomeric GTPases Interact with Rab effector proteins on target membranes |
|
|
Protein synthesis
Integral membrane proteins Secreted proteins Lysosomal proteins Disulfide bonds are formed N-linked glycosylation Major site of phospholipid synthesis takes place in the cytoplasmic face of the ER membrane Detoxification of lipid – soluble compounds cytochrome P450 enzyme Calcium store Calcium is an important signaling molecule |
Endoplasmic reticulum
|
|
|
site of protein synthesis, where ribosomes are attached
|
Rough ER
|
|
|
_________ are sites of lipid metabolism, ER exit sites
|
Smooth ER
|
|
|
__________help proteins to fold(newly synthesized proteins must fold correctly to exit the ER)
Some associate with hydrophobic regions of the emerging peptide this prevents these regions from inappropriately associating with other protein Protein aggregates are bad news |
Chaperones
|
|
|
Protein folding is a difficult process, it is estimated that:
|
1/3 of proteins fold correctly on their own
1/3 of proteins fold correctly with the help of a chaperone 1/3 of proteins are misfolded - these are degraded in proteasomes |
|
|
Some basics about N-linked glycosylation
|
Consensus sequence: N - X - S/T
same oligosaccharide is added every time 2. plays a role in the functioning of the mature protein 3.Also important for proper protein folding increases protein solubility, which discourages aggregation |
|
|
What mediates binding to lectin chaperones?
|
“glyco-code”
|
|
|
Another function of N-linked glycosylation is to
|
marks progress of folding
slow triming of a particular mannose serves as a measure of how long a protein has been in the ER the trimmed oligosaccharide is recognized by the retrotranslocator translocated out of the ER and degraded in the proteasome |
|
|
How is Quality control maintained in the ER?
|
In order to exit the ER proteins must be properly folded
This hides ER retention signals and exposes ER exit signals no large hydrophobic regions should be exposed on the surface Multi-subunit proteins must be properly assembled |
|
|
What is Functional test of quality control in the ER?
|
glutamate receptors bearing a single amino acid mutation in the glutamate binding site are retained in the ER
|
|
|
Trims N-linked sugars
may add further oligosaccaride modifications O-linked glycosylation on some serine or threonine residues Final sorting of protein to their appropriate destinations Transport to the lysosome |
Golgi Apparatus
|
|
|
What are 2 types of Secretion?
|
1. Constitutive – vesicles constantly transported to plasma membrane
2. Regulated – vesicles stored Only released after a signal Examples:Neurotransmitter release Release of insulin |
|
|
large collection of proteases
with central hollow core made of 4 heptameric rings of proteases active sites face into the hollow core in eukaryotes the proteases have different specificites two caps on either end are ATPases that help unfold proteins proteins are degraded into short peptides |
Proteasome
|
|
|
small protein that can be attached to other proteins
|
Ubiquitin
|
|
|
_____________targets proteins to the proteasome for degradation
|
polyubiquitylation
|
|
|
___________are located in the cytoplasm and degrade cytosolic and nuclear proteins
|
Proteasomes
|
|
|
membrane bound organelle filled with degradative enzymes
|
Lysosome
|
|
|
The Internal pH is ~ 5.0 is maintained by...
|
an ATP-dependent H+ pump in the membrane
enzymes are collectively called “acid hydrolases” - have a pH optimum of ~ 5.5 this protects the cell if they are mistargeted or escape in the cytoplasm (pH ~7.2) they will not function well |
|
|
lysosomes degrade contents of vesicles endocytosed from the cell surface by________, _________, and _________.
|
phagocytosis, pinocytosis, receptor-mediated endocytosis
|
|
|
genetic defects in one of the hydrolases or problems targeting them to the lysosome tend to present with neurologic symptoms
Example: Tay-Sachs |
Lysosomal storage diseases
|
|
|
delivers specific molecules to the cell
|
Receptor-mediated endocytosis
|
|
|
What are basic steps in receptor -mediated endocytosis?
|
Low-density lipoprotein (LDL) particles transport cholesterol through the bloodstream
LDL binds to the LDL receptor on a cells surface The LDL / receptor complex clusters in clathrin coated pits and is endocytosed These vesicles fuse with an endosome The early endosome is a sorting compartment Mildly acidic pH causes the LDL to dissociate from its receptor Receptors are recycled to the cell surface LDL particles continue to the lysosome where particle degradation releases the cholesterol (cholesterol can then diffuse out of the lysosome) |
|
|
Familial Hypercholesterolemia is
characterized by |
high blood levels of Low-Density Lipoprotein (LDL) and
premature onset of cardiovascular disease Heterozygous FH ~1 in 500 live births common defect is in cellular uptake of LDL molecules |
|
|
Familial Hypercholesterolemia is caused by a
|
defect is in cellular uptake of LDL molecules
|
|
|
Mutations result in a defect in 3 different points...
|
1. LDL receptor
2. Apolipoprotein B 3. LDLRAP1 ( an adaptor protein that allows the LDL receptor to cluster in coated pits) Patients heterozygous for LDLR mutations develop cardiovascular disease in their 30’s |
|
|
Can treat Familial Hypercholesterolemia with _______ and________
|
1. statins
2. other hypolipidemic agents |
|
|
What are functions of biological lipids?
|
major component of biological membranes
store energy hormones and intracellular signaling molecules anchors for membrane proteins chaperones (to help membrane proteins fold correctly) enzyme co-factors and electron carriers |
|
|
Most biological lipids used to store energy are based on fatty acids and are known as
|
Storage lipids
|
|
|
What are fatty acids?
|
carboxylic acids with a hydrocarbon chain of 4 – 36 carbons
(most common are even numbered chains of 12 – 24 C’s) |
|
|
What are 2 types of hydrocarbon chains?
|
fully saturated with hydrogen ==> contain no double bonds
or can be unsaturated==> have double bonds |
|
|
in most naturally occurring, unsaturated fatty acids
the double bonds are in the__________ |
cis configuration which introduces a kink into the hydrocarbon chain
|
|
|
3 fatty acid molecules, each attached by an ester linkage to a single glycerol are known as ______________
|
Triacylglycerols (or triglycerides)
|
|
|
What are 2 types of triaclglycerols?
|
Simple ==> all three fatty acids are the same
Mixed ==> composed of 2 or 3 different fatty acids Most naturally occurring triglycerides are mixed |
|
|
What are some advantages of using triglycerides to store energy vs carbohydrates (glycogen or starch)?
|
gram for gram triglycerides yield twice as much energy
do not need to carry around water of hydration (2 gm for every gm of polysaccharide) |
|
|
___________contain lipases to break triglycerides down into fatty acids
|
Adipocytes
|
|
|
Molecules need to be_________ to form a lipid bilayer
|
amphipathic
|
|
|
What is the structure of Glycerophospholipids?
|
Backbone=glycerol
C1= fatty acid (ester linkage) C2= fatty acid (ester linkage) C3= polar head group (phosphodiester linkage) |
|
|
many of these_______ will have a net negative charge at physiological pH==> lipid composition effects the surface properties of membranes
|
lipids
|
|
|
A Subclass of glycerophospholipids in which one of the 2 hydrocarbon chains is attached with an ether linkage
|
Ether lipids
|
|
|
____________ is enriched in the heart and is a constituent of myelin
|
Plasmalogen
|
|
|
__________ is released from basophils an stimulates platelet aggregation, and release of seroton ==> important in inflammation and allergic responses
|
PAF
|
|
|
What is structure of Sphingolipids
|
Backbone = sphingosine
C2 = fatty acid (amide linkage) C3 = polar head group (phosphodiester or glycosidic linkage) |
|
|
Sphingolipids include:
|
ceramide, sphingomyelins, cerebrosides, gangliosides
|
|
|
__________ bear a negative charge at physiological pH while the other are neutral
|
gangliosides
|
|
|
_____________play a role in determining ABO blood type
|
glycosphingololipids
|
|
|
Both phospholipids and sphingolipids are degraded in the lysosome
___________attack ester linkages to remove a fatty acid |
Type A phospholipases
|
|
|
Describe Sterols?(i.e. cholesterol)
|
Steroid nucleus = four fused rings
the nucleus is planar and relatively rigid The hydrocarbon body of cholesterol is ~ as long as C16 fatty acid Cholesterol plays a structural role in biological membranes |
|
|
____________ are synthesized from cholesterol and carry signals between tissues.
|
Steroid hormones
|
|
|
__________and__________ transduce signals from activated receptors on the plasma membrane to other parts of the cell
|
Phosphatidylinositol 4,5-bisphosphate and phospholipase C ---known as intracellular signaling
|
|
|
Sphingolipids, such as_______and________ also participate in intracellular signaling
|
ceramide and sphingomyelin,
|
|
|
________ are paracrine hormones
that signal to nearby cells and are all derived from arachidonic acid, a C20 polyunsaturated fatty acid |
Eicosanoids
|
|
|
What are 3 classes of eicosanoids?
|
Prostaglandins, Thromboxanes, and Leukotrines
|
|
|
_________are characterized by a five membered ring
Stimulate contraction of smooth muscles of the uterus during menstruation or labor Produce fever Cause inflammation and pain |
Prostaglandins
|
|
|
___________characterized by a six membered ring containing an ether
Produced by platelets Participate in clot formation Reduce blood flow at the site of a wound |
Thromboxanes
|
|
|
___________ A4 causes contraction of smooth muscle in the airways
Implicated in asthmatic attacks |
Leukotriene
|
|
|
___________block cyclooxygenase,
an enzyme early in the synthetic pathway for prostaglandins and thromboxanes |
NonSteroidal Anti-Inflammatory Drugs (NSAIDS)
|
|
|
What are 2 types of vitamins?
|
Generally divided into water-soluble and fat-soluble
Fat-soluble vitamins include vitamins A, D, E and K |
|
|
_______ is normally synthesized in the skin, with the aid of sunlight
Converted in two enzymatic steps first in the liver and second in the kidney to the active hormone 1,25-dihydroxyvitamin D3 1,25-dihydroxyvitamin D3 is involved in Ca2+ homeostasis |
Vitamin D
|
|
|
β-carotene is the pigment in yellow vegetables that is form of _________
|
Vitamin A
|
|
|
_______is an antioxidant
Aromatic ring destroys free radicals |
Vitamin E
|
|
|
_______is a Blood clotting co-factor
Aromatic ring undergoes a cycle of oxidation and then reduction facilitates activation of thrombin and other clotting factors |
Vitamin K
|
|
|
___________is an electron carrier in inner mitochondrial membrane
|
Ubiquinone (or Coenzyme Q)
|
|
|
Process of vitamin A utilization
in the body |
B-carotene is oxidized to: retinoic acid, a hormone important in development11-cis-retinal, a visual pigment
11-cis-retinal is covalently bound to opsin to form rhodopsin, a seven transmembrane protein Visible light converts 11-cis to all-trans-retinal this conformational change allows G-protein activation |
|
|
__________ defines the external boundaries of a cell
controls molecular traffic into and out of the cell important for cell-cell communication and cell adhesion ==> tissue integrity |
Plasma membrane
|
|
|
__________cluster together with their hydrophobic tails interacting and their polar head groups facing the aqueous environment
|
Amphipathic lipids
|
|
|
_________is favored when the cross-sectional area of the head group
is greater than that of the hydrocarbon chain |
Micelle formation
|
|
|
__________ form when the cross-sectional areas of the head group and the hydrocarbon tail are similar
|
Bilayers
|
|
|
__________ are synthesized from fatty acids in the membrane of the
ER Since they are entirely hydrophobic they accumulate between the leaflets of the ER membrane Eventually a lipid droplet will bud off of the ER ==> droplets are surrounded by a monolayer of phospholipids |
Triglycerides
|
|
|
_________and________ are the major lipid constituents of many membranes and are important for structure
|
Phosphatidylethanolamine and phosphatidylcholine
|
|
|
There are 2 notable exceptions of glycophoslipids that have other fxn's
|
phosphatidylinositiol derivatives are important in intracellular signaling
phosphatidylserine plays a role in clotting (in the platelet)marks a cell undergoing apoptosis, so it can be recognized by phagocytes |
|
|
lipids such as______and_______that are important for signaling tend to be in the inner leaflet
|
phosphatidylinositol derivatives,phosphatidylserine
|
|
|
________ tend to be in the outer leaflet
|
glycolipids
|
|
|
________ have more esoteric functions
and are more minor membrane constituents |
Sphingosine based lipids
|
|
|
What are 3 main types of membrane proteins?
|
integral, peripheral, and lipid anchored
|
|
|
______ have one or more hydrophobic or amphipathic helices that pass through the membrane
|
Integral
|
|
|
________have non-covalent interactions with integral membrane proteins or phospholipid head groups
|
Peripheral
|
|
|
______are covalently attached to a lipid in one leaflet of the membrane
GPI linkage (glycosylphosphotidylinositol glycan anchor) |
Lipid-anchored
|
|
|
________and______ can dissociate (and sometimes re-associate) with the membrane via:
• conformational changes or • enzymatic cleavage |
Peripheral and Lipid-anchored membrane proteins
|
|
|
_______ proteins generally only leave by vesicular transport
|
Integral membrane
|
|
|
How does temperature effect membrane dynamics?
|
Too cool ==> paracrystalline gel phase - very little motion in the membrane
Too warm ==> Liquid-disorderd state interior of bilayer in constant motion Just right (physiological temperature) ==> Liquid-ordered state |
|
|
Some characterisitcs of the Fluid mosaic model
|
both lipids and embedded membrane proteins are free to diffuse laterally in membrane
Shorter hydrocarbon tails ↑ fluidity cis-double bonds ↑ fluidity Rigid sterol nucleus of cholesterol limits motion of hydrocarbon tails and forces them to fully extend ==> somewhat decreases fluidity increases thickness of leaflet Ethanol ↑ fluidity |
|
|
While uncatalyzed lateral diffusion is very fast, movement from one leaflet to another requires __________
This usually uses a transporter and often requires energy |
catalysis
|
|
|
Glycerol based phospholipids are synthesized on the__________
|
cytoplasmic face
|
|
|
Sphingolipids are synthesized in the _____________
|
lumenal face
|
|
|
5 ways to restrict the mobility of a membrane protein are
|
1. Interactions with the cytoskeleton
2. Tight junctions 3. Interactions with the extracellular matrix 4. Interactions with proteins on an adjacent cell 5. Lipid rafts |
|
|
Cholesterol-sphingolipid enriched microdomains in the outer leaflet of the plasma membrane
|
Lipid rafts
|
|
|
__________ typically contain long-chain, saturated fatty acids
|
Glycosphingolipids
|
|
|
______________typically contain one shorter-chain fatty
acid and one unsaturated fatty acid |
Glycerol-based phospholipids
|
|
|
___________ of proteins is believed to functionally organize signal transduction.
|
Lateral segregation
|
|
|
General steps for specific fusion between two membranes : see concept map
|
Steps follow 1-4...also see concept map in notes
|
|
|
Step 1 for specific fusion between 2 membranes(example of neurotransmitter vesicle fusion at the synapse)
|
1. That they recognize each other
vesicleSNARE recognizes and binds to targetSNARE |
|
|
Step 2 for specific fusion between 2 membranes(example of neurotransmitter vesicle fusion at the synapse)
|
2. That their surfaces become closely opposed
==> requires removal of H2O normally associated with polar head groups Helices of vSNARE, tSNARE and SNAP entwine to bring the vesicle close to the pre-synaptic membrane At some point after SNARE binding the process pauses, leaving the vesicles “docked” Ca2+ influx is required to complete the zipping up of the helices |
|
|
Step 3 for specific fusion between 2 membranes(example of neurotransmitter vesicle fusion at the synapse)
|
3. Lipid bilayer becomes locally disrupted favoring fusion of the outer leaflets
When the two membranes are closely opposed fusion of the outer leaflet occurs |
|
|
Step 4 for specific fusion between 2 membranes(example of neurotransmitter vesicle fusion at the synapse)
|
4. Inner leaflets also fuse to form a continuous lipid bilayer
The other leaflet fuses and the bilayer is continuous This creates a pore connecting the lumen of the vesicle with the extracellular space Neurotransmitter is released into the synaptic cleft |
|
|
General info about movement of solutes
|
When two aqueous compartments containing different concentrations of solute are separated by permeable membrane, the solute will move from region
of higher concentration to region of lower concentration ==> it flows down its concentration gradient movement will continue until 2 sides are the same concentration |
|
|
When ions with opposite +,- separated by permeable membrane
ions move across membrane to e = charge on either side (Vm=0) Mvmt of charged solute depends on concentration gradient and electrical gradient (Vm) Known as____________ |
electrochemical gradient
|
|
|
very small, nonpolar molecules (O2, CO2) lipid soluble molecules (steroid hormones)
molecules move down concentration gradient, on their own |
Simple diffusion
|
|
|
diffusion is facilitated by a transmembrane protein mvmt of molecules down electrochemical gradient
DOES NOT use energy example proteins: pores, gated ion channels, passive transporters |
Facilitated diffusion
|
|
|
_____________requires a transmembrane protein able to move molecules against electrochemical gradient
consumes energy example proteins: active transporters (often ATPases) |
Active transport
|
|
|
_________ bind a solute on one side of the membrane
undergo a conformational rearrangement which allows the solute to be released on the other side of the membrane ♦ tend to have lower transport rates ♦ can be saturated |
Transporters (Transmembrane transport protein)
|
|
|
Have transmembrane pore
which can be opened or closed ==> “gated” ♦ have high transport rates ♦ difficult to saturate |
Channels (Transmembrane transport protein)
|
|
|
In ____________nonpolar molecules can diffuse through the lipid bilayer
(no transport protein needed) Molecules will only diffuse down their concentration gradient |
Simple diffusion
|
|
|
embed an ion in a larger molecule
if molecule has hydrophobic surface it can freely diffuse across the membrane. Known as __________ |
Ionophores
|
|
|
Valinomycin(ring of 12 amino acids, purified from bacteria) is K+ selective ionophore that:
|
polar carbonyl groups bind K (selectivity is mainly due to the size of the central cavity) hydrophobic side chains coat the outside
K+ is moved across membrane, down its concentration ∇ this collapses the K+ ∇ across the plasma membrane which interferes with other transporters |
|
|
Zinc pyrithione(zinc ionophore) has several functions including___________
|
increases intracellular zinc concentration
kills bacteria, yeast, fungi used to treat dandruff and fungal infections of the skin (active ingredient of Head & Shoulders) |
|
|
_______ have a pore that is permeable to H20
transport can be in either direction depending on the osmotic gradient Type of facilitated diffusion (passive transport) |
Aquaporins
|
|
|
Aquaproins are crucial for maintaining water homeostasis because:
|
Pore is so narrow that H20 passes in single file
==> too narrow for a hydrated ion to enter ==> ion gradients across the plasma membrane will stay intact |
|
|
insert into the membrane as a tetramer,
but each subunit has its own pore Insertion into the membrane is controlled (pore can not be closed) |
Aquaporins (eleven different types with different tissue distributions and
selectivity-----some pass glycerol or urea better than H20) |
|
|
_________is the glucose transporter in the erythrocyte plasma membrane
|
GLUT1
|
|
|
Glucose is transported into the cell and used in metabolism so the level in the plasma is always(higher, lower, or equal) than in the cell??
|
higher
|
|
|
GLUT1 acts like a conventional transporter
|
1. D-glucose binds in a pocket on the extracellular surface of transporter( this involves many non-covalent interaction- highly specific)
2. Binding of glucose causes conformational change in transporter 3.Exposes glucose to cytoplasm, and lowers affinity of binding site for glucose( glucose diffuses out into the cytoplasm) 4.Release of glucose triggers another conformational change in transporter, which returns to its original conformation |
|
|
____________ shows how primary amino acid sequence forms an amphipathic helix
|
Helical wheel diagram--------see notes!!
|
|
|
The chloride-bicarbonate exchanger in erythrocytes serves to __________the CO2 carrying capacity of the blood
|
increase
|
|
|
For each______ the chloride bicarbonate transports across the membrane, one________ is transported in the opposite direction
|
HCO3
Cl- |
|
|
Cotransporters that move two substrates in the opposite direction are called ______________
|
antiporters
|
|
|
Cotransporters that move two substrates in the same direction are called _____________
|
symporters
Please note: the terms symport & antiport tell you nothing about the energy requirements of the transport |
|
|
__________transport requires energy, usually in the form of ATP and can transport molecules against their electrochemical gradient
|
Active
|
|
|
________active transport directly uses ATP
|
Primary
|
|
|
_______active transport uses an ionic gradient (established by primary active transport) to drive the cotransport of a second solute
|
Secondary
|
|
|
__________ use phosphorylation to drive the conformational change of the transporter
|
P-type ATPases
|
|
|
__________ are transported across the membrane, up their electrochemical gradient
|
Cations
|
|
|
There are more than 70 P-type ATPases, including:_____,______,________ and_______
|
1. Plasma membrane Ca2+-ATPase 2. Na+K+ ATPase
3. H+ pump in parietal cells in the stomach 4. Sarcoplasmic and ER Ca2+ pumps |
|
|
__________are pumps that pump
Ca2+ into the ER |
SERCA pumps
|
|
|
The SERCA pump has 4 domains
|
1. M domain composed of 10 TM helices, provides the path for Ca2+ movement
2. N domain binds ATP 3. P domain contains aspartate residue, which is phosphorylated 4. A domain communicates the movements of the N & P domains to the M Domain |
|
|
Steps involved in activation cycle which uses one ATP to pump two Ca2+ ions into the lumen of the ER......
|
1. Two Ca2+ ions bind with high affinity at the cytoplasmic face of the pump
-ATP also binds to the N domain, which moves close to the P domain 2. The aspartate in the P domain is phosphorylated 3. The phosphorylation leads to a conformational change that is communicated through the A domain to the M domain (the Ca2+ ions are now exposed to the lumenal face of the ER and their binding sites have greatly lowered affinity==> Ca2+ ions diffuse into the lumen of the ER) 4. ADP is released by the N domain 5. The aspartate in the P domain is dephosphorylated 6 & 7. The pump returns to its original conformation |
