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;
408 Cards in this Set
- Front
- Back
What two properties of enzymes does life depend on?
|
-self-replication
-ability to catalyzse reactions efficiently and selectively |
|
Many enzymes depend upon these for functionality
|
cofactors or prosthetic groups
|
|
Enzymes exhibit what for substrates?
|
a high degree of specificity for substrates
|
|
This property of enzymes accelerates chemical reactions tremendously and function in aqueous solution under very mild conditions of temperature and pH.
|
extraordinary catalytic power
|
|
the proteins that efficiently accelerate chemical reactions with a high degree of specificity in biological systems.
|
Enzymes
|
|
complete, catalytically active enzyme complex together with its bound coenzyme and/or metal ions.
|
Holoenzyme
|
|
a coenzyme or metal ion that is very tightly or even covalently bound to the enzyme protein
|
prosthetic group
|
|
protein part of the enzyme without cofactors, or prosthetic groups. The protein is catalytically inactive.
|
Apoenzyme/apoprotein
|
|
inorganic ions (trace nutrients, vitamins, metals) that are required by some enzymes for their catalytic activity.
|
Cofactors
|
|
complex organic or metallo-organic molecules that are required by some enzymes for their catalytic activity
|
Co-enzymes
|
|
molecule that is bound in the active site and is acted on by the enzyme to form product
|
substrate
|
|
area on enzyme containing the amino acid side chains that are involved in catalyzing the reaction.
|
Active Site
|
|
How are enzymes generally named?
|
Substrate first, then type of reaction.
ex. ATP:glucose phosphotransferase |
|
What class/type of reaction catalyzes the transfer of electrons
|
oxidoreductases
|
|
Class enzymes reactions that transfers a functional group to water.
|
hydrolases
|
|
aids in the transfer of groups within molecules to yield isomeric forms
|
isomerases
|
|
Aid in the addition of groups to double bonds or formation of double bonds by the removal of groups
|
Lyases
|
|
What is the most important property of catalysts?
|
There HIGH DEGREE OF SPECIFICITY
|
|
T/F All enzymes are proteins?
|
FALSE- almost all there are a few exceptions
|
|
Enzymes are classified according to what?
|
type of reaction that they catalyze.
|
|
Many enzymes depend upon these for functionality?
|
cofactors or prosthetic groups
|
|
T/F Enzymes increase the rates of chemical reactions and they themselves are changed after the reaction.
|
FALSE: they increase the rate of chemical reactions, but are themselves UNCHANGED after the reaction
|
|
The _____of a chemical reaction is the speed at which it takes place.
|
Rate
|
|
rate in a chemical reaction is equivalent to...
|
the change in the number of moles of starting material or product generated per unit time
|
|
What will happen if the protein is denatured or dissociated into subunits?
|
the catalytic activity is lost
|
|
How does the integrity of the native protein conformation and primary, secondary, tertiary and quaternary structures affect their catalytic activity?
|
They are all essential and must be maintained...if they are disturbed the catalytic activity of the protein is lost.
|
|
Enzyme activity can be regulated through what?
|
covalent modification:
(ex. phosphorylation, glycosylation, etc) |
|
Two distinguishing features of an enzyme-catalyzed reaction:
|
-only takes place within the confines of a pocket called the ACTIVE SITE.
-molecule bound selectively to the active site and acted upon by the enzyme is called the SUBSTRATE. |
|
How do enzymes work?
|
provide a specific optimized environment for chemical reactions to occur more rapidly.
|
|
name two forms of covalent modification
|
phosphorylation
glycosylation |
|
The molecule bound selectively to the active site and acted upon by the enzyme is called...
|
The substrate
|
|
Enzymes increase reaction rates BUT...
|
do NOT affect equilibria
|
|
Enzyme catalyzed reactions occur where?
|
The active site
|
|
What is the function of the amino acids w/ substituent R groups in the active site?
|
bind the substrate and catalyze its chemical transformation.
|
|
The surface of the active site is lined with amino acids with substituent (R) groups that bind the substrate and catalyze its chemical transformation forming what?
|
enzyme-substrate complex
|
|
T/F Some enzymes are responsible for slowing reaction rates.
|
FALSE: enzymes can only SPEED reactions
|
|
Theory that states the rate of reaction is proportional to the frequency of collisions between molecules.
|
Collison theory of chemical kinetics
|
|
Molecules experience repulsive forces when close together collison theory of chemical kinetics states...
|
in order for reactions to occur energies must be high enough to overcome these repulsive forces
|
|
the more substrate you add...
|
the more likely a reaction will occur.
|
|
True/False: The position and direction of equilibrium is positively affected by enzymes.
|
FALSE: Equillibrium is NOT affected in any way by enzymes.
|
|
the starting point for either a forward or reverse chemical reaction
|
ground state
|
|
The equilibrium between Substrate and Products ground states is reflective of ...
|
the difference in the free energies of their ground state. (ΔG).
|
|
When the products ground state is lower than that of the substrates, the standard free energy change for the reaction is _________.
|
negative –( it reflects a favorable reaction equilibrium, and the equilibrium favors P)
|
|
When a reaction of substrate to product results in a decrease in the ground state of the product what is released? And what type of reaction is it?
|
Heat; exothermic reaction
|
|
When the ground state of the product results in a lower energetic state than you started with the product is said to be MORE or LESS stable than the substrate?
|
MORE
|
|
The position and direction of equilibrium are ____ affected by any enzyme or catalyst.
|
NOT!!!!!!
|
|
When the standard free energy state for a reaction is negative, will the reaction favor product or substrate?
|
product
|
|
Reaction that releases heat
|
exothermic reaction
|
|
In order to make a reaction go backwards from product to substrate when the Product is at a lower energy level what would need to happen?
|
You would need to put MORE ENERGY into the reaction than you got out of it in the first place.
|
|
The rate of a reaction is dependent on what?
|
the activation energy
|
|
To undergo reaction in either direction, the molecules must be...
|
raised to a higher energy level to overcome the barrier or hill between substrate and product. (ex pushing rock over hill; it takes more energy to go back up the hill in reverse)
|
|
The reaction energy path controls what?
|
reaction speed
|
|
energy required for formation of transient unstable charges, bond rearrangements, and other transformations required for the reaction to proceed in either direction.
|
energy barrier or energy hill between Substrate and product.
|
|
state when the molecules raised to a higher energy level reach the top of the energy hill, there is a point at which decay to the S or P state is equally probable.
|
transition state
|
|
Activation energy determines...
|
the rate of the reaction
|
|
difference between the energy levels of the ground state and the transition state is called
|
activation energy
|
|
Molecular moment when events such as bond breakage, bond formation, and charge development reach the transition state what is possible?
|
The decay to either substrate or product is EQUALLY possible
AKA transition state |
|
a higher activation energy corresponds to a (faster/slower) reaction.
|
SLOWER
|
|
The point in which decay to either substrate or product is equally likely.
|
transition state
|
|
energy requirement for reaction to occur
|
activation energy
|
|
Reaction rates are dependent upon what?
|
level of activation energy
|
|
______ _______ are linked to the standard free-energy change for the reaction (ΔG’o).
|
Reaction equilibria
|
|
Reaction energy path controls what aspect of the reaction?
|
SPEED
|
|
Reactants are at a MORE/LESS stable reaction rate than the products?
|
Less stable
|
|
The lower the activation energy the ________ the reaction.
|
Faster
|
|
Reaction rates can be increased by?
|
-Raising the temperature (increasing free energy of ground state)
-lowering the activation energy (by adding an enzyme) |
|
How does rasing the temperature increase the reaction rate?
|
by inreasing the number of molecules wioth sufficient energy to overcome the barriers
|
|
enzymes do what to the activation energy?
|
Lower it.
|
|
How do enzymes decrease the activation energy?
|
by forming enzyme-substrate (ES) complexes and enzyme-product (EP) complexes. accelerating the inter-conversion of S and P, this is a bi-directional catalyzing reaction
|
|
The interconversion of Substrate and product is a __________ catalyzing reaction.
|
bidirectional
|
|
When several steps occur in a reaction, the overall rate is determined by the step with the highest activation energy, this step is called the
|
Rate limiting step
|
|
When multiple enzymes are utilized and there are many steps if the activation energys are similar it is considered...
|
partially rate limiting
|
|
Despite being energy barriers to chemical reactions, activation energies are important because they...
|
-Without this barrier, complex macromolecules would revert to much simpler molecular forms spontaneously and higher ordered structures and metabolic processes of cell could not exist.
-Enzymes selectively lower activation energies for reactions that are needed for cell survival to occur at the right place and at the right time. |
|
enzymes SELECTIVELY do what to activation energy for processes needed for cell survival?
|
Lower it.
|
|
Enzymes have extraordinary catalytic power: they can
greatly enhance a reaction rate by |
as much as 17 orders of magnitude (10 to 17th )
|
|
The ability of enzymes to descriminate and act on a specific substrate is due to there...
|
HIGH degree of SPECIFICITY to their substrate
|
|
Major source of energy for dramatic lowering of the activation energies comes from...
|
binding energy from weak, noncovalent interactions between substrate and enzyme, as a specific enzyme-substrate (ES) complex is formed during reaction.
|
|
What stabilizes and maintains the interactions between E and S in the ES complex?
|
(hydrogen bonds, hydrophillic,hydrophobic and ionic interactions, etc.
|
|
Formation of these weak interactions in the ES complex is accompanied by release of a small amount of free energy that provides a degree of stability to the interaction, called...
|
binding energy
|
|
enzymes active sites are complementary not to the substrates but to ...
|
the substrates TRANSITION STATE during the reaction. (not exactly the lock and key idea)
|
|
Interaction with enzyme and substrate typically involves
|
a change in conformation which brings specific functional groups on the enzyme into position to catalyse the reaction (ex of induced fit)
|
|
enzyme’s active site has
functional groups arranged optimally to form a variety of weak interactions with a particular substrate in the transition state, and forms |
enzyme substrate complex
|
|
molecular agents that
interfere with catalysis, slowing or halting enzymatic reactions. |
enzyme inhibitors
|
|
Two broad classes of enzyme inhibitors
|
- reversible (competitive or uncompetitive)
- irreversible (noncompetitive) inhibitors. |
|
competes with the substrate for the active site of an enzyme
|
competitive inhibitor
|
|
What forms an EI complex and what does it do?
|
When competitors resembling the substrate combine with
the enzyme. It prevents catalysis form occurig. (REVERSIBLE by adding more substrate) |
|
binds covalently with or
destroys a functional group on an enzyme that is essential for the enzyme’s activity. |
Non-competitive inhibitor
|
|
a special class of irreversible
inhibitors. They are relatively un-reactive until they bind to the active site of a specific enzyme. |
suicide inactivators
|
|
How does a suicide inactivator work?
|
undergoes the first few chemical steps of the normal enzymatic reaction, but instead of being transformed into the normal product, the
inactivator is converted to a very reactive compound that combines irreversible with the enzyme. |
|
How can competitive inhibition be overcome?
|
Add more substrate
|
|
Well designed suicide inactivator is...
|
-specific for a single enzyme
-un-reactive until it is within that enzyme’s active site. |
|
Charachteristics of saturation kinetics.
|
-Enzyme activity expressed as micromol of substrate converted to product per minute
-Initial velocity of the reaction (enzyme-catalyzed) is dependent upon the concentration of substrate. -concentration of substrate increases, velocity (V) increases. -Velocity increases until the enzyme is completely saturated. |
|
When all the active sites are filled with substrate we are at
|
Maximum velocity or Vmax
|
|
When substrate molecule is in the active site it sits there until...
|
the reaction is complete. The product is then released.
(lock and key theory) |
|
As the concentration of substrate increases velocity does what?
|
INCREASES
|
|
The reaction is limited by
|
the availability of enzymes.
|
|
This occupies the binding pocket of the enzyme, but is not changed by it.
|
Inhibitor
|
|
disassociates from the binding pocket and can be replaced by a molecule of the normal substrate or by another molecule of inhibitor.
|
competitive inhibitor
|
|
When all active sites are filled with substrate does the inhibitor effect Vmax.
|
NO but it does increase the Km (concentration of substrate that produces half max velocity)
|
|
Increase in Km, combined with the absence of effect on Vmax is a characteristic feature of
|
Competitive Inhibition
|
|
What is Km
|
the concentration of substrate that produces half max velocity
|
|
involves formation of a covalent bond between the binding site and the inhibitor.
|
irreversible inhibition (non-competitive)
|
|
Why do Irreversible inhibitors lower the Vmax but not the Km?
|
inhibitor acts as if it removes active enzyme from the reaction, which would decrease max velocity due to lack of enzyme for available substrate
|
|
When all active sites are filled with substrate
|
Vmax
|
|
Charachteristics of Regulatory enzymes.
|
-exhibit increased or decreased catalytic activity in response to certain signals;
-have a greater effect on the rate of the overall metabolic sequence; -in most multi-enzyme systems, the first enzyme of the sequence is usually a regulatory enzyme. |
|
they function through reversible, noncovalent binding of regulatory compounds.
|
Allosteric compounds
|
|
activities of regulatory enzymes can be
modulated by... |
-by allosteric compounds
-reversible covalent modification |
|
regulatory enzymes for which
substrate and modulator are identical. |
Homotropic
|
|
regulatory enzymes for which the modulator is a molecule other than the substrate
|
Heterotropic
|
|
T/F: the modulators for allosteric enzymes may be inhibitory or stimulatory.
|
TRUE
|
|
Most allosteric enzymes have how many subunits?
|
two or more
|
|
allosteric enzymes generally have one or more regulatory, or allosteric sites specific for
|
binding the modulator
|
|
substrate binding sites and modulator binding sites on some allosteric enzymes are on different subunits called
|
C (catalytic) and
R(regulatory) subunits |
|
How is the binding of the positive modulator to its specific site on the regulatory modulator communicated?
|
its communicated to the catalytic subunit through conformational change
|
|
What happens when the regulatory modulator dissociates from its regulatory subunit?
|
the enzyme reverts to its inactive or less active form
|
|
The substrate modulator relationship is __________
|
Bidirectional- a conformational change in one side will cause a conformational change in the other side
|
|
When regulatory enzymes are specifically inhibited by the end product of the
pathway. |
feedback inhibition
|
|
What is the most common type of covalent regulatory modification?
|
Phosphorylation : 1/3 to 1/2 of all proteins can be phosphorylated
|
|
function of protein kinases
|
Catalyzes the attachment of phosphoryl groups to specific amino acid residues of a protein
|
|
Function of Protein Phosphatases
|
Catalyses the removal of phosphoryl groups
|
|
Phosphorylation is...
|
a type of regulatory modification
|
|
why is an enzyme required for removal of a phosphoryl group?
|
b/c the covalent bond that was formed in phosphorylation is permanent so an enzyme is required to initiate that reaction. --protein phosphatease
|
|
Glycogen phosphorylase occurs in two forms:
|
-more active phosphorylase a
-less active form b. (unphosphorolated) |
|
The breakdown of glycogen in skeletal muscle and the liver is regulated by:
|
variations in the concentration of the two forms of glycogen phosphorylase.
|
|
Describe the two subunits of Phosphorylase a
|
Each has a specific Ser residue that is phosphorylated at its hydroxyl group.
|
|
How does phosphorylase phosphatase remove phosphoryl groups?
|
They are hydrolytically removed
|
|
how is phosphorylase a converted to phosphorylase b?
|
cleavage of two serine phosphate covalent bonds:
|
|
Can phosphorylase b be reactivated?
|
YES
|
|
By what mechanism is phosphorylase b reactivated?
|
phosphorylase kinase.
covalently transforms it into active phosphorylase a |
|
catalyzes the transfer of phosphoryl groups from ATP to the hydroxyl groups of the two specific Ser residues.
|
Phosphorylase kinase
|
|
amphipathic means the molecule contains?
|
– hydrophilic (polar) end and a hydrophobic end (non-polar)
ex. Lipid membrane |
|
Functions of lipids:
|
-structural components
-energy source -storage for energy ie. fat cells -chemical messengers -regulate critical biological properties -shock absorbers |
|
How do lipids serve as chemical messengers?
|
hormone steroids, prostaglandins between body tissues
|
|
How do lipids in cell membranes contribute to structure?
|
regulate flow of H2O, ions, and other molecules into and out of cell
|
|
By what mechanism to lipids contribute to regulating critical biological processes/
|
Through solubility of Vitamins A, D, E, K
|
|
Lipids do what in relation to fat soluble vitamins?
|
aid in their absorption and transport.
|
|
Cholesterol is building block for ...
|
many steroids and hormones
|
|
Fatty acids are considered...
|
hydrophobic and insoluble in water BUT are still considered Amphipathic b/c they have acidic charged end which makes them able to interact with water and form hydrogen bonds
|
|
Charchteristics of saturated hydrocarbons
|
-long chain fatty acid
-NO double bonds -all carbons are Saturated with hydrogens -typically higher melting points -Room temp typically solids -no kink in tail b/c no double bonds |
|
Charachteristics of Unsaturated fatty acids
|
-long chain fatty acids
-contains double bonds -lower melting points generally -typically liquids at room temp ex. canola oil -kinks in structure created by double bonds. -less hydrophobic interactions b/c kinks so MORE fluid |
|
Esters of fatty acids with glycerol.
- NOT polar or amphipathic – they are hydrophobic. What am I? |
Triglycerides
|
|
Triglycerides are important in the body for...
|
metabolism
building blocks energy sources |
|
How are micro signaling environments formed on the cellular membrane?
|
via membrane proteins and cytoskeleton elements on the lipid bilayer
|
|
What is the chemical composition of membranes?
|
Lipids and proteins are the two major components of all membranes
-small amount of various polysaccharides in the form of glycoprotein and glycolipid -contain NO FREE carbohydrates (they must be covalently bonded to the hydrophillic portion of lipid membrane or proteins) |
|
Lipid structure of biological components varies according to what?
|
the constituients that make up that particular membrane, its portions of each and there charachteristics.
|
|
circular structure that form single lipid layer of fatty acid tails towards center and hydrophillic heads on outside.
|
Micelle
|
|
Micelles are important for what processes?
|
digestion of lipids in the body
|
|
A bilayer that creates ball with hydrophillic heads on outside and hydrophillic area in center
|
Liposome
|
|
Liposome is important for what processes?
|
endocytosis when something needs a way out of cell but needs to be preserved within a hydrophillic medium
ie. to transport signaling molecules or when things need to be transported for recycling, Typically pinched off and packaged from golgi apparatus |
|
3 Major lipid components of eukaryotic membranes
|
-Glycerophospholipids
-Sphingolipids -Cholesterol |
|
The Most Abundant Lipids of Membranes
|
Glycerophospholipids:
ie. phospholipids for short |
|
a prototypical glycerophospholipid contains?
|
Glycerol molecule with a phosphate esterified at the a-carbon
two long-chain fatty acids Amphipathic – hydrophilic (polar) end and a hydrophobic end (non-polar) |
|
fatty acids are attached to glycerol molecule in phospholids by what type of bond?
|
Phosphodiester bridge
-O-P-O- |
|
Phosphatidic acid
|
the most basic of glyceral phospholipids the bond attached to the phosphate bond is a hydrogen
|
|
Describe a phosphodiester bridge
|
2 Carbons attached by two oxygens with Phosphate in center
|
|
important signaling molecule for G protein coupled signaling
|
PIP2
|
|
Process of making Phosphatidic acid
|
glycerol 3 phosphate joined by 2 acetyl Co A groups w/ help of acetyltransferase
|
|
two mechanisms of syntesizing Phospholipids
|
1st- dephosphorylate the head groups and activate them with CTP to release CMP
2nd- activate DIACYLGLYCERATE w/ CDP first |
|
When the head groups are activated FIRST in the formation of phospholipids what groups can result?
|
Phosphatidyl-CHOLINE
-ETHANOL -LSERINE |
|
Enzyme involved in forming Phosphatidic acid
|
acetyltransferase
|
|
When the DIACYLGLYCEROL is activated FIRST in the pathway to formation of phospholipids what is the result?
|
Phosphotidyl-LINOSITAL
Phosphotidylglycerol Cardiolipin |
|
T/F: there are ways the phospholipids can be interconverted to make what the body needs
|
True
ex. if we are deficient in choline body can make phosphotidycholine from methylating ethanolimine |
|
High energy bonds in the form of ATP or CMP are utilized to make phospholipids T/F
|
True
|
|
Functions of Phospholipids
|
-membrane components
-signaling molecules -surfactant -platelet activating factor |
|
Signaling functions of phospholipids
|
-phosphotidylinositides
-Arachadonic acid metabolism -others not covered in this class (THANKFULLY!!) |
|
When Phospholipase C (PLC) is activated via hydrolysis what two important signaling molecules result?
|
DAG (Diacylglycerol)
IP3 (Inosital 1, 4,5 triphosphate) |
|
What molecule resulting from PIP 2 stays attached to the membrane?
|
Diacylglyceral (DAG)
which is an important signaling molecule |
|
What does Phosphoinositide signaling entail?
|
Phosphoinosital kinase (PI kinase) utilizes ATP to make PIP which is then converted to PIP2 by PIP kinase
|
|
PIP2 is hydrolysed to make what signaling molecule?
|
IP3 (Inositol triphosphate)
|
|
What is the role of IP3 in the release of Ca2+ into the cell?
|
IP3 which is water soluble moves through cytosol to bind receptor in ER causing conformational change and the opening and then release of Ca into cell.
|
|
Describe G protein coupled signaling
|
hormone binds to receptor outside cell- GDP -GTP exchange-activates PLC(phospholipase C on membrane)- cleaves PI to IP3-binds to ER-Ca2+ release then produces response to hormone
|
|
T/F Diacylglycerol and IP3 both have signaling ability within the cell
|
TRUE
|
|
What enzme does DAG activate?
|
Protein Kinase C which is a Calcium dependent enzyme
|
|
Role of Protein Kinase C in the cell
|
Can cause phosphorylation of proteins within the cell
|
|
Name examples of processes dependent on Phosphoinositide.
|
Angiotensin
Vasopressin histamine oxytocin alpha 1 adrenergic TRH Platelet derived growtth F. |
|
Pulmonary surfactant is a a mixture of...
|
- phospholipids, primarily dipalmitoyllecithin, and proteins that decrease the surface tension of water in the pulmonary alveoli
|
|
Dipalmitoyllecithin
|
spreads out on the water in the alveoli with the phosphate group/choline in the water and the lipid tails pointing away from the water. This keeps water molecules on opposite sides of the alveoli from coming into contact and forming hydrogen bonds with each other.
|
|
Cleaves IP3 from diacylglycerol
|
Phospholipase C
|
|
Role of surfactant
|
decrease surface tension of water
|
|
What is surfactant made of
|
Phosphatidylcholine (Lecithin) and some other lipids
|
|
How does surfactant reduce surface tension in the alveoli
|
prevents water molecules in different parts of the alveoli from interacting and producing hydrogen bonds which would promote increase surface tension
|
|
Do the lipid tails of surfactant point towards the air or fluid interface?
|
towards the air interface; the phosphate/choline groups are polar and interact with water
|
|
Describe the structure of Platelet Activating factor
|
3 carbon molecule with:
-ether linked alkane on 1st Carbon -acetyl ester attached to 2nd Carbon -phosphate attached to 3rd carbon with a choline molecule attached to it. |
|
What purpose does the acetylester group serve on the Platelet activating factor molecule?
|
Makes it more water soluble
|
|
-Synthesized and released by activated immune cells.
-Mediates many allergic/anaphylactic symptoms. -utilizes G protein coupled receptor for activation and signaling |
Platelet activating factor
|
|
-derived from the aliphatic amino alcohol sphingosine
-signal transmission and cell recognition |
sphingolipids
|
|
Spingolipids role in action potential propagation
|
-mks sphingomylin which is wrapped around the neuron
-important in action potential propagation |
|
compact, rigid, hydrophobic molecule with four fused rings
-c branched hydrocarbon chain attached to D ring -polar hydroxyl group at C3 |
cholesterol
|
|
what makes cholesterol amphoteric?
|
the steroid nucleus is hydrophobic and the polar hydroxyl group is hydrophillic
|
|
Function of cholesterol in the membrane
|
alters the fluidity of membranes and participates in controlling the microstructure of plasma membranes
|
|
Increasing cholesterol in membrane (increases/decreases) fluidity of membrane
|
decreases fluidity
(the steroid group makes the membrane less fluid b/c it interacts) |
|
As you INCREASE temp of membrane the cholesterol will do what to membrane
|
maintains the structure longer so it alters (increases) the melting point of the membrane. Helps keep the structure in the face of the increased temperature.
|
|
AT very LOW temperatures what does the cholesterol do to the membrane
|
prevents stability at low temperatures. So it maintains the membrane at LOW temperatures
|
|
T/F: ALL steroid hormones are synthesized from Cholesterol.
|
FALSE: ALL EXCEPT Estradiol
|
|
Steroids interaction with water and its hydrophillic properities come from what structure?
|
The polar hydroxyl group which is available for esterification
|
|
Once esterification of the hydroxyl group occurs how does this affect the cholesterol molecule?
|
It is NO LONGER polar so it is no longer Amphopathic
-ie. its less soluble |
|
Components of Cholesterol molecule
|
-Alkyl side chain
-Polar head group (OH group) -steroid nucleus |
|
Which is the only steroid with an aromatic ring attached?
|
Estradiol- which is synthesized from testasterone by the enzyme Aromatase
|
|
Are Esters soluble?
|
NO
|
|
How do statins prevent the formation of Cholesterol?
|
provide HMG Coenzyme reductase which helps to prevent formation of cholesterol
|
|
What is the rate limiting step in the formation of cholesterol?
|
HMG Co enzyme reductase
|
|
What are the building blocks of Mevalonate and what is it important in forming?
|
3 Acetyl Co A's combine and form HMG Co A in the formation of cholesterol fromdietary fatty acids
|
|
What is added to Mevalonate to make Isoprene?
|
ATP is utilized to add 3 phosphates resulting in Isoprene which is then isomerized
|
|
What structure is cyclized to form cholesterol?
|
Squalene which is a linear structure. this requires a lot of energy in form of NADPH
|
|
What is combined to make squalenes in the process of forming cholesterol?
|
Isoprenes are combined with the aid of phosphates and NADPH
|
|
Lipids are transported in what?
|
Myocele
|
|
Name 4 mechanisms of Lipid transport
|
-chylomicrons
-HDL -LDL -VLDL |
|
Responsible for Exogenous fat transport
|
Chylomicron
|
|
An LDL precursor
|
VLDL
|
|
Responsible for cholesterol transport
|
LDL
|
|
Responsible for Reverse cholesterol transport
|
HDL2 and HDL3
|
|
-Synthesized in small intestine
-Transport dietary lipids -98% lipid, large sized, lowest density -Apo B-48 Receptor binding -Apo C-II Lipoprotein lipase (LPL) activator -Apo E Remnant receptor binding |
Chylomicrons
|
|
Synthesized in liver
Transport endogenous triglycerides 90% lipid, 10% protein Apo B-100 Receptor binding Apo C-II LPL activator Apo E Remnant receptor binding |
VLDL
|
|
Synthesized from VLDL during VLDL degradation
Triglyceride transport and precurser to LDL Apo B-100 Receptor binding Apo C-II LPL activator Apo E Receptor binding |
IDL
|
|
-Synthesized from IDL
-Cholesterol transport from liver to extrahepatic tissue -78% lipid, 58% cholesterol & CE -Apo B-100 Receptor binding |
LDL
|
|
-Synthesized in liver and intestine
-Reservoir of apoproteins -Reverse cholesterol transport -52% protein, 48% lipid, 35% C & CE -Apo A Activates lecithin-cholesterol acyltransferase (LCAT) -Apo C Activates LPL -Apo E Remnant receptor binding |
HDL
|
|
Takes extra cholesterol from tissues to transport it to liver for degradation by bile salts
|
HDL
|
|
Apo B 100 binds to its LDL receptor and the cell engulfs it to bring the LDL back into the cell via endosome which is referred to as...
|
cell mediated endocytosis
|
|
dephosphosphorylates HMG CoA reductase which increases its activity to drive reaction to produce cholesterol
|
INSULIN does this.
|
|
Role of ACAT in cholesterol regulation
|
ACAT = ac-CoA-cholesterol acyl transferase (makes cholesterol esters from ac-CoA). which increases the amount of cholesterol synthesized
|
|
How are LDL's removed from the blood stream
|
cell mediated endocytosis after binding to the LDL receptor via APO B
|
|
dietary cholesterol + newly synthesized cholesterol – cholesterol excretion.
|
= TOTAL Cholesterol
|
|
How does Glucagon regulate Cholesterol?
|
Keeps HMG CoA reductase in its LESS active state which inhibits cholesterol synthesis
|
|
In states of Low ATP cholesterol synthesis is...
|
DOWN REGULATED
|
|
In states of high cholesterol LDL can inhibit the formation of more by what mechanism?
|
by inhibiting receptor mediated endocytosis via Negative feedback inhibition (preventing uptake of LDL)
|
|
In states of High ATP or high energy states cholesterol will be...
|
UP regulated- so more will be made
|
|
Cardiovascular risk is correlated with
|
-total cholesterol and with LDL cholesterol.
-and INVERSELY with HDL levels |
|
How can you impact Total Cholesterol?
|
-decreasing dietary cholesterol,
-decreasing cholesterol synthesis (statins) -increasing cholesterol elimination (cholestyramine). |
|
What drugs inhibit HMG COA reductase?
|
Statins
|
|
what does high LDL do to your cardiovascular risk?
|
INCREASES the risk
|
|
What does low HDL do to your cardiovascular risk?
|
INCREASES your risk
|
|
What does HIGH HDL do to your cardiovascular risk?
|
DECREASES your risk
|
|
Can Choloesterol be degraded? Can it be used as fuel?
|
NO and NO
|
|
What do cholestyramine's do?
|
Increase cholesterol elimination
|
|
How do you dispose of Cholesterol?
|
through the bile, either as free cholesterol or as bile acids.
|
|
How does Cholestyramine effect the elimination of cholesterol?
|
-bind bile acids in the intestine and prevent reabsorption.
|
|
What do bile acids do to cholesterol?
|
solubilize the free cholesterol and prevent the formation of cholesterol gall stones. Preventing the reabsorption of cholesterol in the intestines
|
|
How does Glucagon affect HMG Coa Reductase and what is its impact on cholesterol synthesis?
|
Glucagon will keep HMG coA reductase in LESS active state. Inhibiting the synthesis of cholesterol.
|
|
In what form are carbohydrates incorporated into membranes?
|
present in membranes primarlily as oligosaccharides covalently attached to proteins to form glycoproteins
(Less common, CHO is attached to lipids to form glycolipids) |
|
What are the primary constituients on the outer side of the membrane?
|
phosphatidylcholine and sphingomylin
|
|
Where does the process of Gprotein coupled receptors and IP3 pathways occur?
|
Inner layer of the membrane
|
|
What major components make up the inner layer of the membrane?
|
Phosphatidyl ETHANOLAMINE
Phosphatidyl SERINE Phosphatidyl LINOSITOL Phosphatidic Acid |
|
Enzymes that promote the transverse movement of lipids from one layer to the other
|
Lipid transporters
|
|
What is a "flip flop" diffusion?
|
A SLOW uncatalyzed reaction when the ipid flip flops from one side of the membrane to the other
|
|
when transverse flip flopping happens FAST what aids this process?
|
the enzyme FLIPPASE
|
|
What is lateral diffusion of a lipid in a membrane and is it catalyzed?
|
When a lipid moves laterally in the same side of the membrane.
FAST despite it being UNCATALYZED |
|
Fluidity of a membrane is dependent on what?
|
Interaction of the phospholipds
-composition -Temperature -Head group size/charge -FA length (shorter inc. fluidity) -cis double bonding (kink inc. fluidity) -Cholesterol (dec. fluidity …..yet prevents freezing |
|
Why does the fluidity have to be precisely regulated and How?
|
The fluidity has to be precisely regulated as numerous membrane processes are fluidity dependent (e.g., enzymes, channels)
Diet as well as several anesthetics act to alter membrane fluidity. |
|
What things are membrane proteins?
|
pumps, channels, enzymes, glycoprotein's, cytoskeletal elements, etc.
|
|
How are membrane proteins classified?
|
Often times on the basis of ease of their removal from isolated membrane fractions
|
|
What type of protein is a multi transmembrane helices?
|
Integral protein that spans both sides of the membrane
|
|
Peripheral or extrinsice proteins are typically ______
soluble |
water
|
|
How can peripheral proteins be released from the membrane?
|
by treatment with salt solutions of different ionic strength or extremes of pH.
|
|
Integral (or intrinsic) proteins contain sequences of what?hydrophobic amino acids, which create hydrophobic domains that interact with the hydrophobic hydrocarbons of the lipids and stabilize the protein–lipid complex.
|
hydrophobic amino acids, which create hydrophobic domains that interact with the hydrophobic hydrocarbons of the lipids and stabilize the protein–lipid complex.
|
|
Is it easy or hard to denature or release an intergral protein? What can accomplish this?
|
HARD -drastic treatment, such as use of detergents or organic solvents
|
|
Name ways that peripheral proteins are attached to the membrane
|
-bound to an integral protein
-through electrostatic interactions - attached by a short terminal hydrophobic sequence of amino acids -attached by a covalently bound lipid |
|
T/F: Many enzymes that are integral membrane proteins require a membrane lipid for activity.
|
TRUE
|
|
How does Glucagon affect HMG Coa Reductase and what is its impact on cholesterol synthesis?
|
Glucagon will keep HMG coA reductase in LESS active state. Inhibiting the synthesis of cholesterol.
|
|
In what form are carbohydrates incorporated into membranes?
|
present in membranes primarlily as oligosaccharides covalently attached to proteins to form glycoproteins
(Less common, CHO is attached to lipids to form glycolipids) |
|
What are the primary constituients on the outer side of the membrane?
|
phosphatidylcholine and sphingomylin
|
|
Where does the process of Gprotein coupled receptors and IP3 pathways occur?
|
Inner layer of the membrane
|
|
What major components make up the inner layer of the membrane?
|
Phosphatidyl ETHANOLAMINE
Phosphatidyl SERINE Phosphatidyl LINOSITOL Phosphatidic Acid |
|
What lipid does the enzyme D- b-hydroxybutyrate dehydrogenase, located in the inner mitochondrial membrane require to function?
|
phosphatidylcholine
|
|
FA’s stimulate the release of what from the ryanodine receptor
|
Ca 2+
|
|
Gasses diffuse through the lipid membrane based on what?
|
The concentration gradient
|
|
How does water diffused through a biological membrane?
|
via nonspecific movement through ion channels, pores are around membrane proteins. Aquaporins- renal tubule cells, large protein pores, allow high rate of water flow (osmotic forces
|
|
In order for diffusion of a solute with strong interaction with water molecules to occur what needs to happen first?
|
shell of water surrounding the solute must be stripped away before it enters the lipid milieu and then regained on leaving the membrane.
|
|
Distribution of hydrophobic substances depend on what?
|
degree of lipid solubility of the substance
|
|
How are membrane translocation systems classified?
|
- involve intrinsic membrane proteins and are classified on the basis of their mechanism of substrate translocation and the energetics of the system
|
|
Channels are...
|
-voltage regulated
-agonist regulated -cAMP regulated or other |
|
Name an example of a voltage regulated channel
|
Na + channel
|
|
name an example of an agonist regulated channel
|
Acetylcholine receptor
|
|
name an example of a cAMP regulated channel
|
Cl- channel
|
|
T/F: Channels can also be stretch, pressure and heat sensitive
|
True
|
|
Transporter translocation systems can be either
|
Facilitated or
Active (primary and secondary) |
|
How do channels and Pores in membranes function differently?
|
Pores- NOT selective, (as long as substance is smaller than pore it will pass through)
-Channels are selective for specific inorganic cations and anions (Selectivity filter is due to size of the aqueous area created in the protein structure as well as amino acid residues lining the channel area) |
|
What is the major protein in purified preparations of gap junctions?
|
connexin
|
|
When depolarization of one group of muscle cells rapidly spreads to adjacent cells.
-Occurs in cardiac and smooth muscle cells |
Electrical Coupling
|
|
What is it called when Cyclic AMP readily passes through gap junctions and thus, hormonal stimulation of one cell can lead to signal propagation to a cluster of cells.
|
Metabolic coupling
|
|
name 2 stimuli for rapid closure of connexons in Gap junctions
|
Elevated intracellular calcium and low intracellular pH
|
|
How does communication between heart cells occur?
|
gap junctions
|
|
Where are Na activated channels present and why are they important?
|
- Plasma membrane of neurons, heart and skeletal muscle: important for excitability
-Sense electrical gradients -Selectivity filter is due to size of the aqueous area and amino acid residues lining the channel area: Specific AA environment makes it “cozy” for sodium - Selective of sodium over other monovalent or divalent cations |
|
What determines the selectivity filter in a voltage gated sodium channel?
|
-size of the aqueous area
-AMINO ACID RESIDUES lining the channel area |
|
How do excitable cells change the depolarization of the membrane?
|
By allowing the passage of Na via voltage gated channels
-when the membrane is polarized the channel closes |
|
How are Nicotinic Acetylcholine Receptors activated?
|
They are LIGAND GATED activation channels.
-Acetylcholine released from the motor neuron diffuses to the muscle membrane and binds to the Ach R (receptor) |
|
Describe how the Nicotinic Acetylcholine receptor functions
|
Bulky hydrophobic Leu side chains close the channel. When 2 Acytacholines bind the the M2 helices twist and the channel opens with polar residues lining the channel
|
|
Translocate the molecule or ion across the membrane by binding and physically moving the substance.
-no chemical rxn occurs |
Membrane transporters
|
|
movement of solute occurs spontaneously.
(Down concentr gradient via diffusion) DG is negative ( down the [gradient] ) |
Facilitated transport
-doesnt require added energy |
|
requires the input of some energy source for movement of the solute
Hydrolysis of ATP to ADP Utilization of an electrochemical gradient of Na+ or H+ across the membrane. (secondary active transport) DG is positive |
ACTIVE TRANSPORT
|
|
Transporters have _________ for the substance to be transported, and can be inhibited by both ________and _________inhibitors.
|
specificity
can be inhibited by competitive and non-competitive inhibitors |
|
movement down the concentration gradient can be
|
passive transport of facilitated diffusion
|
|
active transport
|
movement against the concentration gradient.
-requires the addition of energy |
|
With both channels and transporters the molecule is ___________ following translocation across the membrane.
|
unchanged
|
|
Steps in facilitated transport: Uniport
|
1. recognition
2. transport(when bound substance induces a conformational change) 3. Release(occurs if concentration of subtance in new envrion is lower OR a decrease in affinity for the substance) 4. Recovery(transporter returns to orig conformation) |
|
Example of a Uniport transport in the body
|
Glu T2 (glucose transport from blood to tissue)
|
|
What are the two types of Co-transport?
|
Symport
Antiport |
|
Transporter itself is coupled directly itself to hydrolysis of ATP
|
Primary active transport
|
|
Requires (move S into cell against concentr gradient) its coupled here to movment of something else its
NOT directly coupled it depends on hydrolysis and ATP from another process. |
Secondary Active Transport
|
|
Name an example of primary active transport
|
Na/K ATPase
|
|
Glucose transport across the gut is an example of what type of transport?
|
Secondary active transport
|
|
What is the driving force for the Na+ glucose symporter?
|
high extracellular Na levels.
Symporter takes two Na molecules in and it drags a glucose molecule with it. (Secondary active transport) |
|
What HAPPENS to the molecule during TRANSLOCATION?
|
MODIFIED
|
|
All amino acids can be transported by group translocation EXCEPT...
|
PROLINE
|
|
When Amino Acids are TRANSLOCATED across the membrane where does the energy to do this come from?
|
hydrolysis of a peptide bond in glutathione.
|
|
How many ATP molecules are utilized to Resynthesize Glutathione?
|
3 ATP's
|
|
What is group translocation?
|
Group translocation is an expensive energetic mechanism for transport of amino acids across the membrane.
-(important to note the molecule is modified) |
|
SIMPLE DIFFUSION
|
NON-polar compounds only
DOWN the concentration gradient |
|
Facilitated Diffusion
|
DOWN the ELECTROCHEMICAL gradient
|
|
Primary Active transport
|
AGAINST the ELECTROCHEMICAL gradient
|
|
Secondary Active transport
|
against the electrochemical gradient. DRIVEN by ion moving DOWN its gradient
|
|
movement down electrochemical gradient, may be gated by a ligand or ion
|
Ion channel
|
|
Ionophore mediated ion transport
|
down electrochemical gradient
Ionophores change the environment to mask the polarity in order to move things (polar moiety on the inside) |
|
Prostaglandins and related compounds are collectively known as...
|
Eicosanoids
|
|
Most Eicosanoids ("local" hormones) are produced from...
|
arachidonic acid, a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid).
|
|
Function of Eicosanoids...
|
-specific effects on target cells close to their site of formation rapidly degraded, so they are not transported to distal sites within the body.
involvement in intracellular signal cascades. |
|
prostaglandins
prostacyclins thromboxanes leukotrienes epoxyeicosatrienoic acids. ARE ALL ex of... |
EICONASOIDS
|
|
EICONASOIDS have roles in:
|
inflammation
fever regulation of blood pressure blood clotting immune system modulation control of reproductive processes & tissue growth regulation of sleep/wake cycle. |
|
a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid).
|
ARACHADONIC ACID
|
|
participates in INTERCELLULAR signaling
|
EICONASOIDS
|
|
WHAT enzyme can cleave the bond releasing Arachadonic Acid?
|
Phospholipase A2
|
|
How is phospholipase A2 activated
|
A number of receptors activate phospholipase A2 THROUGH G-PROTEIN COUPLED receptors
|
|
Where are many metabolites of Arachadonic Acid located?
|
(in the 2 position of several phospholipids in membranes).
|
|
Corticosteroids are anti-inflammatory because
|
prevent INDUCIBLE PHOSPHOLIPASE A2 expression reducing arachidonate release.
|
|
Platelet Activating Factor (ACTIVATES OR DEACTIVATES) some phospholipase A2 varients
|
ACTIVATES
|
|
Why has it been difficult to develp drugs that inhibit isoforms of phospholipase A2
|
Success has been limited by the diversity of Phospholipase A2 enzymes, and the fact that arachidonate may give rise to inflammatory or anti-inflammatory eicosanoids in different tissues.
|
|
T/F: There are multiple Phospholipase A2 enzymes, subject to activation via different signal cascades.
|
TRUE
|
|
Arachidonic acid is acted on by this enzyme which results in Prostaglandins and then Thromboxanes
|
CYCLOOXYGENASE (COX)
|
|
Arachidonic Acid is acted on by this enzyme to make Leukotrienes, HETE and Lipoxins
|
LIPOXYGENASE
|
|
Arachidonic acid is acted on by these enzymes to make Epoxides to DiHete and Hete
|
CYTOCHROME P450's
|
|
How are prostaglandins synthesized
|
Once arachidonic acid has been clipped from the phospholipid, it can be acted on by cyclooxygenase to make prostaglandins and from them, thromboxanes.
|
|
How do ASA and Ibuprofin work?
|
They inhibit COX and interrupt that pathway
|
|
This COX is expressed in activated immune cells.
|
COX 2
|
|
THis COX is expressed in the stomach, the kidney, platelets, and other places
|
COX 1
|
|
What COX enzymes to NSAIDS inhibit?
|
most inhibit COX 1 and COX 2
|
|
What are many of the undesirable effects of NSAIDS due to? ex (ulcers)
|
Inhibition of COX1
|
|
If an NSAID was strictly a COX 2 inhibitor would it ideally exhibit any undesirable effects?
|
NO those are typically due to inhibition of Cox 1
|
|
What accounts for the analgesic activity of NSAIDS?
|
b/c Prostaglandins sensitize nociceptors to pain stimuli therefore if you INHIBIT cox you inhibit the production of Prostaglandins
|
|
How do NSAIDS get there anti-inflammatory properties?
|
Prostaglandins also mediate some of the inflammatory effects of activated immune cells (COX-2), so NSAIDs are anti-inflammatory.
|
|
How do NSAIDs prevent platelet aggregation?
|
Prostaglandins (thromboxane A2) promote platelet aggregation (COX-1), so NSAIDs prevent it.
|
|
how do NSAIDS alleviate menstrual cramps?
|
Prostaglandins (except prostacyclin) promote smooth muscle contraction – NSAIDs help with menstrual cramps.
|
|
Thromboxanes are synthesized from...
|
Prostaglandin
|
|
What is the structure of Thromboxane?
|
6-membered ring containing an ether.
|
|
What produces Thromboxanes
|
platelets
|
|
What are thromboxanes important in?
|
clotting and in vasoconstriction proximal to a vessel injury.
|
|
What do NSAIDS do to the production of Thromboxane?
|
THey INHIBIT the production of thromboxane
|
|
Found in Leukocytes this enzyme catalyzes conversion of arachidonate to 5-HPETE (5-hydroperoxy-eicosatetraenoic acid).
|
5-Lipoxygenase
|
|
5-HPETE is converted to __________, which in turn may be converted to various other leukotrienes
|
leukotriene-A4
|
|
Leukotrienes have roles in
|
inflammation
|
|
implicated in asthmatic constriction of the bronchioles.
|
LEUKOTRIENES
|
|
produced in areas of inflammation in blood vessel walls as part of the pathology of atherosclerosis.
|
LEUKOTRIENES
|
|
How do Leukotrienes perform their action?
|
Some act via specific G-protein coupled receptors (GPCRs) in the plasma membrane.
|
|
Anti-asthma medications include:
|
-inhibitors of 5 Lipoxygenase, e.g., Zyflo (zileuton)
-drugs that block leukotriene-receptor interactions.E.g., Singulair (montelukast) & Accolate (zafirlukast) block binding of leukotrienes to their receptors on the plasma membranes of airway smooth muscle cells. |
|
In the case of asthma meds they work by
|
PREVENTING the interaction thus preventing the cascade and signaling that leads to constriction.
-(They do not PREVENT PRODUCTION of the molecule) |
|
HOW DO GENES PLAY INTO ALL THIS??
|
You may think that has nothing to do with lipids – lipids are not proteins.
BUT the lipids are synthesized to their various forms by the activity of enzymes, which are proteins encoded by their respective genes. |
|
Disorders of lipid metabolism are caused when...
|
the genes that encode particular enzymes are mutated so the resulting proteins can’t do their job properly.
|
|
How does Aspirin work?
|
binds to cyclooxygenase and prevents the binding of arachidonic acid.
|
|
How do statins work?
|
bind to the binding pocket of HMG CoA reductase and prevent the binding of HMG-CoA.
|
|
KIDS IT ALL COMES DOWN TO THE...
|
GENES
|
|
Three functions of muscle tissue
|
-movement and stabilisation
-storage and movement of substances within the body -generation of heat |
|
Properties of muscle tissue
|
-electrical excitability
-contractility -extensibility (unique to muscle tissue) -elasticity |
|
surrounds entire muscle
|
epimysium
|
|
surrounds fasciculi
|
perimysium
|
|
surrounds individual muscle fibres and is
continuous with tendons and aponeuroses |
endomysium
|
|
responds to certain stimuli by transmission of action potentials
|
muscles: electrical excitability
|
|
shortening of muscle to generate tension
|
Contractility
|
|
Property of muscle that is unique to ONLY muscle tissue in body
|
Extensibility
can be stretched without damage |
|
property of muscle: returns to original shape after contraction or extension
|
Elasticity
|
|
Continuous with tendons and aponeuroses
|
endomysium
|
|
Nerves and blood vessels travel through ______ ______ to the muscle fibres.
|
connective tissues
|
|
conveys impulses for muscular contraction at
Neuromuscular junction |
motor neuron
|
|
provide nutrients and oxygen for contraction
|
blood vessels
-each muscle fibre is in contact with one or more capillaries |
|
Contents of skeletal muscle fibrs
|
-Sarcolemma
-Transverse tubules -Sarcoplasmic reticulum (specialized endoplasmic retic) -Sarcoplasm -myoglobin -Multiple nuclei -Myofibrils -Other organelles |
|
specialized for the sequestering and release of Calcium that drives contraction
|
sarcoplasmic reticulum
|
|
muscles way of extracting oxygen when in high demand for high energetic use
|
Myoglobin
|
|
contractile proteins they are specialized in muscle to do contraction
|
myofibrils
|
|
Myofibrils consist of...
|
-Contractile proteins
Organized into myofilaments Actin - thin myofilaments Myosin - thick myofilaments -Regulatory proteins Troponin Tropomyosin |
|
Structure of Myofibril
|
Approximately 1mm in diameter
Extend in parallel rows from one end of muscle cell to the other Composed of repeating assemblies of overlapping thick (myosin) and thin (actin) filaments Alternating zones of actin and myosin give rise to the term striated |
|
synthesized in a globular form called G-actin which aggregates to form F-actin, or fibrous actin
|
Actin
|
|
rod shaped protein w/ two distinct subunits
-interacts with thin filament and transmits signal for conformational change to other components upon Ca2+ binding |
Tropomyosin
|
|
One is bound to each individual Tropomyosin
|
Troponin
|
|
name two contractile proteins in a myofibril
|
Actin
Myosin |
|
Name two regulatory proteins present on myofibril that muscle contraction depends on.
|
Troponin
Tropomyosin |
|
What is the function of Tropomyosin?
|
helps to stabilize the thin filament and to transmit signals for conformational change to other components of the thin filament upon Ca2+ binding.
|
|
Describe the function of the Tropomyosin's 3 different subunits
|
-The Tn-T subunit binds to tropomyosin.
-The Tn-I subunit is involved in the inhibition of the binding of actin to myosin in the absence of Ca2+. -The Tn-C subunit, a calmodulin-like protein, binds Ca2+ and induces a conformational change in Tn-I and tropomyosin, resulting in exposure of the actin–myosin-binding sites |
|
whats the function of the two heads on myosin?
|
two globular heads on one end
-The globular head section of myosin contains 1. an ATPase that provides energy for contraction and 2. the actin-binding site |
|
Function of the light chains on myosin
|
The light chains are “calmodulin-like” proteins that bind calcium and can modulate myosin activity
essential (alkali) Ca2+ binding EF hand motif (calmodulin like) regulatory (phosphorylatable via MLCK) to regulate myosin fxn. |
|
-a structural protein that Stabilizes position of thick filament
-Coiled aspect provides elasticity and extensibility |
Titin
|
|
in muscle this structural protein forms M-line which binds thick filaments together
|
Myomesin
|
|
Structural protein that links thin filaments to integral proteins of sarcolemma
Sarcolemmal proteins attach to proteins in connective tissue surrounding muscle fibre Transmits force to surrounding connective tissue |
Dystrophin
|
|
skeletal muscle contraction
|
Within the skeletal muscle cell, force production is tightly coupled to the level of myoplasmic calcium.
-quiet state, most cellular calcium is in the sarcoplasmic reticulum (SR) leaving the myoplasmic Ca2+ concentration ([Ca2+]i) at approximately 50nM. At this level of ([Ca2+]i) no detectable force is generated by the contractile apparatus. Depolarization of the cell results in a rapid release of SR Ca2+ which progressively saturates the actin filament Troponin C binding sites thus initiating force production. Maximal force production is realized when [Ca2+]i reaches 5-10 µM. |
|
what is released to trigger an action potential at the NMJ?
|
Acetylcholine released at junction
Depolarises sarcolemma leading to generation of muscle action potential |
|
Where does neuromuscular transmission occur?
|
Specialized synapse between a motoneuron and a muscle fiber
Occurs at a structure on the muscle fiber called the motor end plate |
|
Axon terminal sits here it is
-20-30 nm wide - contains large quantities of acetylcholinesterase (AChE) |
synaptic cleft
|
|
they increase the surface are of the post synaptic membrane
-Ach gated channels at tops -Voltage gated Na+ channel in bottom half |
subneural cleft
|
|
Sequence of events initiated by an action potential
|
Action potential-opening of voltage gated Ca channels-Ca enters presynaptic terminal initiates release of Ach from synaptic vessels-diffusion of Ach across synaptic cleft binding to receptors on the postsynaptic permeability of ligand gated Na channels- Increase in Na permeability results in depolarization of membrane. ONCE THRESHOLD has been reached a postsynaptic action potential results
|
|
After the acetycholine binds and causes opening of Na channels what happens to it?
|
its rapidly broken down in the synaptic cleft by acetylcholinesterase to acetic acid and choline.
|
|
How do local anesthetics block conduction in sensory motor neurons?
|
They reversibly bind to Na voltage gated channels, particularly the activation gate, reducing the ability of the membrn to depol.
|
|
How do curariform drugswork?
|
Curariform drugs (D-turbocurarine) block nicotinic ACh channels by competing for ACh binding sites. Reduces amplitude of end plate potential therefore, no AP
|
|
How does Myasthenia gravis cause muscle weakness?
|
occurs when Ach receptors are blocked and destroyed by antibodies in an autoimmune condition.
|
|
How do tetanus and botulin toxin cause muscle weakness?
|
They cause paralysis by blocking neuro- transmission. They are proteases that digest components of the vesicle fusion process and prevent exocytosis and release of the transmitter. Botulism prevent the release of Ach and tetanus blocks inhibitory synapses.
|
|
contractile proteins are activated by
|
EC coupling processes
|
|
skeletal muscle contracts according to
|
the sliding filament theory
|
|
What unmasks the bindng site on actin
|
the tropomyosin slides deeper into the actin groove exposing the site.
|
|
Energy for muscle contraction is supplied by...
|
ATP Hydrolysis
|
|
If the metabolic process is insufficient to keep up with the energy demand, the _________ ________ system serves as a “buffer” to maintain cellular levels of ATP.
|
creatine phosphokinase
|
|
catalyzes transfer of phosphate from phosphocreatine to ADP in an energetically favored manner:
|
creatinine phosphokinase
|
|
T/F: normal muscle tissue, the concentration of ATP in sarcomere remains fairly constant even during strenuous muscle activity.
|
TRUE
|
|
Energy for muscle contraction is supplied by
|
ATP hydrolysis by myosin–ATPase
ATP hydrolysis by SERCA ATP binding to RyR |