Physiology Flashcards
Hypokalemia
K+
Hyperkalemia - more of a concern- muscle weakness/paralysis. cardiac arrythmia - usually arises from kidney failure and inabilty to secrete K+ TOO MUCH Potassium
is when blood’s potassium levels are too low. Potassium is an important electrolyte for nerve and muscle cell functioning, especially for muscle cells in the heart. Your kidneys control your body’s potassium levels, allowing for excess potassium to leave the body through urine or sweat.
Plasma normal range?
It makes up about 55% of the body’s total blood volume.
3.5 - 5 to maintain membrane potential
??
electrogenic? producing a change in the electrical potential of a cell.
moving K+ out of cell, creates a charge imbalance “electrogenic”
receptor potential?
mechanosensors, olfactory receptors, photoreceptors
Plasma osmolalaity?
295-300 miile osmoles/KG
what human cells do not reproduce?
neurons, heart cells, skeletal muscle cells and red blood cells.
can smooth muscles reproduce?
Yes - Smooth cells have the greatest capacity to regenerate of all the muscle cell types. The smooth muscle cells themselves retain the ability to divide, and can increase in number this way. As well as this, new cells can be produced by the division of cells called pericytes that lie along some small blood vessels.
autocoids?
autocoids” are biological factors (molecules) which act like local hormones, have a brief duration, and act near their site of synthesis.
Paracrine signaling
is a form of cell signaling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells.
operons?
An operon is made up of several structural genes arranged under a common promoter and regulated by a common operator. It is defined as a set of adjacent structural genes, plus the adjacent regulatory signals that affect transcription of the structural genes.
Signal transduction
(also known as cell signaling) is the transmission of molecular signals from a cell’s exterior to its interior. Signals received by cells must be transmitted effectively into the cell to ensure an appropriate response. This step is initiated by cell-surface receptors.
what’s in a cell? H2O
PMP
water - 2/3 of body’s water, and high in potassium, magnesium, phosphate
ecm? rich in?
1/3 water, large amounts of sodium, chloride, bicarbonate, oxygen, glucose, fatty acids, amino acids, carbon dioxide
body mass - % water?
60%
feedback system of body - 3 parts
receptor - reports to Central Control,
control center (brain or endocrine) evaluates and sends out orders,
effector - receives orders and complies
negative feedback in body
if something is excessive or deficient - attempts to return things to normal
positive feedback - leads to?
INstability - initiating change - ie blood clotting is good to stop a rupture, but it needs to stop or it can do bad things
cell membranes - allow lipid soluable substances to enter like?
CO2, O2, fatty acids, steriod hormones
keeps out water soluable - ions, glucose, amino acids
cell membrane made of mainly?
lipids and proteins - proteins fulfull many roles - trasnport, enzymes, hormones, antigens, ion and water channels, etc
amphipathic
glycerol backbone head, two fatty acid tails -
both hydro phillic and phobic
how does cholesterol affect cell membrane?
As temperature increases, so does phospholipid bilayer fluidity.
increases flex and stability, controls fluidity depending upon temperature -
Cholesterol reduces permeability of lipid membranes. … Cholesterol plays has a role in membrane fluidity but it’s most important function is in reducing the permeability of the cell membrane. Cholesterol helps to restrict the passage of molecules by increasing the packing of phospholipids.
protein components of cell membrane?
integral (channels, pores, transport proteins, receptoss G proteins)
peripheral - loosely attached to intra or extra cellular side by electrostatic interaction - not covalently bound
transport into/out of cell - 3 types
- bulk
endocytosis - pino, phago, receptor mediated
exocytosis
- passive - simple or facilitates (w carrier) NO ATP reqa
- Active - Uphill transport - needs energy - primary and secondary
pinocytosis - bring things into cell
vesicles formed -
via clathrin coating, latticework of actin and myosin - ATP and Ca++ required (to pinch)
both pinocytic and phagocytic vesilces may contain lysossomes and thus are
digestive organs of cells
phagocytosis
only some cells can do this - initiated when particle (bacterium) attached to antibody which is attached to outside of cell via opsonization - bring into cell, merge with lysosome - digest -
molecular gradients
outside cell - NA+, CL-
inside K+, PO4 (phosphate), proteins
diffusion - when stop?
how many kinds?
when dynamic equil reached - particular are uniform thruout
Simple and Facilitated
simple diffusion -
passes through pores or right thru membrane if lipid soluble -
down concentration gradient -
factors: concentration, velocity, kinetic movement, number and size of openings
typical lipid soluble molecules?
O2, nitrogen, CO2, alcohol - dissolve directly in lipid bilayer - large amounts of of O2 transported this way - as if no membrane
water soluble molecules - need pores
Net diffusion - continues until become equal -
depends on -
size of concentration gradient,
partition coefficient?
diffusion coefficient
thickness of membrane
surface area available -
other factors - electrical gradient - if molecule is charged (if heading into an area with opposite charge - will go faster, more easily)
temperature
molecule mass (high mass - moves more slowly)
Membrane permeability
partition coefficient
Larger the number - the easier it gets thru
the greater the relative solubility in OIL - the higher the coefficient
non-polar solutes have higher values
Diffusion coefficient
Larger the number - the easier it gets thru
size of molecule vs. viscosity of medium -
small solute in nonviscous solution has a larger diffusion coefficient
thicker the membrane ?
greater the distance to travel - lower the rate of diffusion
greater the surface area?
easier, faster the diffusion
factors that increase permeability?
oil/water coefficient
radius (SIZE) of solute
Membrane thickness, viscosity of membrane
Fick’s Law of Diffusion
J=A/T x S x change ? P
Net diffusion
J = PA (Ca - Cb)
J - net rate
P - permeability
A - surface area
Ca concentration of solute 1
Cb - concentration of solute 2
osmolarity
number of particles into which a solute disassociates
does glucose disassociate?
No, so it’s osmolarity is 1 ?? IT is equal to its molarity
if a solute disassociates into more than one particle - then osmolarity =s molarity x number of particles - ie NaCL is 2 mOsml/lt
carrier mediated transport (all but simple diffusion)- 3 qualities
saturation
stereospecificity ?? L vs D
competition
is facilitated diffusion faster or slower than simple diffusions
at low solute concentrations - faster - but then levels off as binding sites become saturated -hence curves - vs simple just keeps going up
example of facilitated diffusion?
Glut 1 - RBC, BBB 2 - liver, pancreas, kidney 3 neurons 4 - fat, muscle - insulin 5 - testis and ?
Glut 4 transporter of glucose into skeletal muscles - glucose can be transferred as long as two things:
- glucose level higher in blood than ICF
- binding sites not saturated
does simple diffusion exhibit stereospecifity?
no - it allows both D and L to get thru - all others do NOT - only D is allowed to bind
three examples of primary active transport?
Na+ - K+ ATPase (all cells)
Ca2++ ATPase in sarcoplasmic and endoplasmic reticulum
H+K+ ATPase in gastric parietal cells
Na+-K+ pump
positivity continually pumped out - getting rid of positive NA+
“electrogenic”
cycles between E1 and E2 (E2 faces ECM) E1 requires ATP, not sure about E2
three sodium out, 2 potassium in - this is always happening and keeping the cells at these artificial levels (maintains concentration gradient) - ?? where does cell keep getting its sodium to kick out?
digitalis and ouabain- cardiac glycosides
inhibits NA+K+ pump - binds at E2 sites - stopping cycling
Cardiac glycosides are a class of organic compounds that increase the output force of the heart and increase its rate of contractions by acting on the cellular sodium-potassium ATPase pump.
Ca2++ ATPase pump
SERCA
most cells pump Ca out - 1 CA out for ATP used
sarcoplasmic and endoplasmic retic - pump 2 CA out for each ATP hydrolyzed
has an E1 and E2 site like NA/K pump -
H+/K+ parietal cells - and alpha-intercalated cells of renal collecting ducts -
Omeprazole - inhibits - reduces secretion of H+ for peptic ulcers
in stomach - pumps H+ from ICF of parietal cells into lumen - where acidifies
Secondary transport
transport of two or more solutes coupled - usually Na+ moves downhill and other solutes moves uphill - downhill provides the energy - ATP not used directly (Na+ to move downhill needs ATP??)
two types of secondary transport -
cotransport (symport)
countertransport (antiport or exchange)
cotransport example
glucose intestinal absorption - must bind to both glucose and Na+ simultaneously in the lumen of small intestine
countertransport example
GR - three positive charges move into cell in exchange for two positive out -
three NA+ enter, 2 Ca leave
electrogenic (producing a change in the electrical potential of a cell.)
Ca++ pumping out of cell in sarcoplasmic reticulum - must bind to both Ca and NA simultaneously to create transport
diabetes I example in book
GR - glucose NOT excreted thru urine - but is in diabetes - transporter not working, not reabosrbing glucose in Prox tubule -
insulin helps with reabsorption of glucose - but pt. lacking -
so more and more glucose is produced - and when levels high - are filtered in kidney -
and levels too high for capacity for Na+glucose transporter to transport all - so
excreted in urine
Note that if the solute is CHARGED - and coming into the cell - like an electrolyte or ion - two things may change
- net rate of diffusion will be changed depending upon the charges and how they add up
- diffusion potential
Osmosis
flow of water across semipermeable membrane beca of difference in solute concentration - occurs because of pressure difference
difference between osmosis and diffusion?
Diffusion - there is more water in one place than another
In diffusion, particles move from an area of higher concentration to one of lower concentration until equilibrium is reached. In osmosis, a semipermeable membrane is present, so only the solvent molecules are free to move to equalize concentration.
Osmosis and aquaporins
Vasopressin - Antidiuretic hormone
lots of AQP2 in kidney collecting ducts - vasopressin (hormone) increases water transport to inserting more AQP2 in apical plasma membrane
Nephrogenic diabetes - rare inherited, but can develop in people taking
LITHIUM
both conditions asso w/ lack of AQP2 in collecting ducts
kidney loses ability to reabsorb water properly - excessive loss of water - very dilute urine (polyuria)
amounts of solute expressed :
moles, equivalents, osmoles
CONcentrations of solute, expressed in
moles/Liter (millimoles mmol/L)
Equivalent/L, MilliEquivalent mEQ/L
Osmoles per liter (Osm/L), milliosmoles - mOsm/L
1 mole - vs an equivalent vs osmole
1 mole - 6x10(23)
Equivalent - amount of charged solute - numbers of charged solute multiplied by its valence
1 osmole - number of particles into which a solute dissociates
osmolarity vs osmolality
similar number - osmoLALITY is KG _note both lality and KG (v liter) come first in alphabet
Osmolality is what in ICF vs ECF?
SAME! 285 - 290 mOsm/Kg
typical plasma osmolarity is 295
Osmolarity?
A solution with low osmolarity has a greater number of water molecules relative to the number of solute particles; a solution with high osmolarity has fewer water molecules with respect to solute particles
Molarity (M)
is the amount of a substance in a certain volume of solution. Molarity is defined as the moles of a solute per liters of a solution. Molarity is also known as the molar concentration of a solution.
if solution doesn’t dissociate?
osmolarity = molarity
300 mM glucose - 300 mOsm
What are compounds that completely dissociate in water?
Substances that dissolve in water to yield ions are called electrolytes. Electrolytes may be covalent compounds that chemically react with water to produce ions (for example, acids and bases), or they may be ionic compounds that dissociate to yield their constituent cations and anions, when dissolved.
Osmolarity = g x C
osmolarity - concentration of particles
g - number of particles / mole
C - concentration
Isomotic solutions
solutions that have same calculated osmolarity
hyperosmotic - vs hypo
solution with higher osmolarity vs lower
Nernst potential - no net flow of ion from one side of membrane to another
Equilibrium refers to the fact that the net ion flux AT A PARTICULAR VOTAGE is zero.
the magnitude of the Nernst potential is determined by the ratio of the concentrations of that specific ion on the two sides of the membrane.
the reversal potential (also known as the Nernst potential) of an ion is the membrane potential at which there is no net (overall) flow of that particular ion from one side of the membrane to the other. … Equilibrium refers to the fact that the net ion flux at a particular voltage is zero.
nernst potential for sodium, potassium, calcium
intracellular vs extra concentrations
sodium +60
potassium -90
calcium +137
sodium 15
potassium 150
calcium 70
resting potentials of sodium, potassium, calcium
sodium -90
potassium
how do you calculate Nernst potential? aka reversal potential
The Nernst equation is often used to calculate the cell potential of an electrochemical cell at any given temperature, pressure, and reactant concentration.
This is done by simply dividing the current at each voltage by the driving force, which is the voltage minus the reversal potential (V − Vrev). Furthermore, reversal potential calculations can also signify how well the cell is voltage clamped
what does nernst equation compare?
find the what voltage is that can offset concentration gradient
where ions will flow when have both a chemical concentration gradient and an electrical concentration gradient - and predicts where the ions will flow
When can a second action potential be generated?
when inactivation gates of sodium channels begin to open up - in relative refractory period.
What is equilibrium potential?
net flow of zero ions because charge is balanced
Driving Force
Ions, atoms or molecules that have a charge, can be affected by an electrical driving force. This force across a cell membrane is expressed as the membrane potential. This potential results from an unequal distribution of charges across the membrane.
How is electrochemical driving force determined?
When an ion is not at its equilibrium, an electrochemical driving force (VDF) acts on the ion, causing the net movement of the ion across the membrane down its electrochemical gradient. The driving force is quantified by the difference between the membrane potential and the ion equilibrium potential (VDF = Vm − Veq.).
What is the equilibrium potential for K+?
K+ will be in electrochemical equilibrium when the cell is 90 mV lower than the extracellular environment.
K+ is a positively charged ion that has an intracellular concentration of 120 mM, an extracellular concentration of 4 mM, and an equilibrium potential of -90 mV; this means that K+ will be in electrochemical equilibrium when the cell is 90 mV lower than the extracellular environment.
The resting potential of a myelinated nerve fiber is primarily dependent on the concentration gradient of which of the following ions?
K+
what potassium disorder reduces the Na/K+ pump?
HYPOkalemia
digitalis also inhibits pump
The activity of the Na+-K+ pump is reduced in hypokalemia, not hyperkalemia.
Hypokalemia is when blood’s potassium levels are too low. Potassium is an important electrolyte for nerve and muscle cell functioning, especially for muscle cells in the heart. Your kidneys control your body’s potassium levels, allowing for excess potassium to leave the body through urine or sweat.
Resting potential - determined by concentrations between two sides
NOT by permeability?
In most neurons the resting potential has a value of approximately −70 mV. The resting potential is mostly determined by the concentrations of the ions in the fluids on both sides of the cell membrane and the ion transport proteins that are in the cell membrane
What is isotonic and hypertonic?
Hypertonic SUCKS
Water flows from hypo to hyper!
If a cell is placed in a hypertonic solution, water will leave the cell, and the cell will shrink. In an isotonic environment, the relative concentrations of solute and water are equal on both sides of the membrane. … When a cell is placed in a hypotonic environment, water will enter the cell, and the cell will swell.
is urea hypo or hypertonic?
Effective vs ineffective osmoles -
can they draw fluid across a membrane?
Effective - YES
Mannitol can draw CSF out of brain -
glucose, naCL also Effective
Ineffective - doesn’t cause water movement -
Hypo - RBCs will explode
An effective osmole is one that is UNABLE to cross from the Extracellular fluid (ECF) to the Intracellular fluid
- It will generate an osmotic force that draws fluid across a membrane.
- Effective osmoles include: NaCl, Glucose, Mannitol
- An ineffective osmole will contribute to total plasma osmolality but because it
can freely move from the ECF to ICF, it generates no osmotic pressure.
• A classic example of an ineffective osmoles are Urea, Ethanol
Reflection coefficient
varies from 1 to zero
zero - Zero osmatic pressure - membrane is freely permeable
(σ) - an index of the effectiveness of a solute in generating an osmotic driving force. of a solution to pull water across a biologic membrane. Example: Ethanol can accumulate in body fluids at sufficiently high concentrations to increase osmolality by 1/3, but it does not cause water movement.
two ineffective osmoles -
Zero reflection coefficient
do not pull water -
urea and ethanol
Transport of D- and L-glucose proceeds at the same rate down an electrochemical gradient by which of the following processes?
Only two types of transport occur “downhill”—simple and facilitated diffusion. If there is no stereospecificity for the D- or L-isomer, one can conclude that the transport is not carrier-mediated and, therefore, must be simple diffusion.
sodium potassium pump - 3 what are pumped out ?
3 sodium - so there!
How does the sodium calcium exchanger work?
three sodium ions are exchanged for each calcium,
The exact mechanism by which this exchanger works is unclear. It is known that calcium and sodium can move in either direction across the sarcolemma. Furthermore, three sodium ions are exchanged for each calcium, therefore a small (few millivolt) electrogenic potential is generated by this exchanger.
How is glucose taken up in the small intestine?
COTRANSPORT
The classical pathway of glucose absorption is across the intestinal brush-border membrane (BBM), which was predominantly mediated by SGLT1, a membrane protein that couples two molecules of Na+ together with one molecule of glucose.
How do you calculate partition coefficient?
A partition coefficient is the ratio of the concentration of a substance in one medium or phase (C1) to the concentration in a second phase (C2) when the two concentrations are at equilibrium; that is, partition coefficient = (C1/C2)equil.
water flows in which direction?
A hypotonic solution has a lower concentration of solutes than another solution.
from hypotonic to hypertonic
A 23-year-old man is brought to the Emergency Department after collapsing during basketball practice. On admission he is lethargic and appears confused. His coach reports that it was hot in the gym and he was drinking a lot of water during practice. An increase in which of the following is the most likely cause of his symptoms?
Drinking water after losing a significant volume
of water as sweat decreases the osmolality of the extracellular fluid
because the salt lost from the extracellular fluid in sweat is not replaced by
the ingested water. When the extracellular osmolality is decreased, water
flows from the extracellular to the intracellular body compartment, causing
intracellular volume to increase. The patient’s symptoms are caused by
swelling of the brain.
solute used to decrease intercranial pressure?
manitol
Mannitol, a hypertonic crystalloid solution, is commonly used to decrease brain water content and reduce intracranial pressure (ICP). Hypertonic saline solutions also decrease brain water and ICP while temporarily increasing systolic blood pressure and cardiac output.
If the extracellular K+ concentration is increased from 4 meq/L to 10 meq/L,
??
The membrane potential will become more negative
Inactivation of the sodium-potassium pump will cause
a. An increase in the intracellular volume
will allow Na ions to accumulate in the cell, as K ion will fall. So this creates a depolarization in the cell membrane.
Membrane excitability will be increased by the greatest amount by
a. Increasing extracellular Na+
The resting potential of a nerve membrane is primarily dependent on the concentration gradient of
a. Potassium
Which of the following statements best characterizes a molecule whose reflection coefficient to a membrane is zero?
It is as diffusible through the membrane as water - but will not pull water
Which of the following words or phrases is most closely associated with an end-plate potential at the neuromuscular junction?
b. Depolarization
In a nerve, the magnitude of the action potential overshoot is normally
a function of the
c. Extracellular sodium concentration
The amount of force produced by a skeletal muscle can be increased by
d. Decreasing the interval between contractions
The velocity of nerve conduction is increased with a decrease in the
Capacitance of the nerve fiber membrane
The rate of diffusion of a particle across a membrane will increase if
The lipid solubility of the particle increases
Periodic hyperkalemic paralysis is characterized by high potassium concentration and muscle weakness. Which of the following is likely to cause muscle weakness as a result of increased extracellular potassium concentration?
Inactivation of sodium channels in muscle cells
The flow of calcium into the cell is an important component of the upstroke phase of action potentials in
skeletal muscles
Which of the following will be less during the overshoot of an action potential than during the resting state?
Transference for potassium
Preventing the inactivation of sodium channels will decrease
c. The downstroke velocity of nerve cell action potentials
Statements descriptive of both the equilibrium and steady states include which of the following?
a. The sum of all the fluxes across the membrane is zero in both
An increase in sodium conductance is associated with
The end-plate potential of the skeletal muscle fiber
Electrically excitable gates are normally involved in
e. Increase in nerve cell potassium conductance caused by an increase in extracellular potassium
The sodium gradient across the nerve cell membrane is
Used as a source of energy for the transport of other ions
Increasing the extracellular potassium concentration will
a. Increase the threshold for eliciting an action potential
Which of the following would cause an immediate reduction in the amount of potassium leaking out of a cell?
Increasing (hyperpolarizing) the membrane potential
WHY??
Excitation-contraction coupling in smooth muscle is initiated when calcium binds to
calmodulin
In which one of the following transport processes is the substance moving down its electrochemical gradient?
Glucose into adipose tissue
??
Nitric oxide produces many of its physiologic effects by stimulating the synthesis of
b. Cyclic GMP
Hyperpolarizing the membrane makes the inside of the cell more
negative and therefore ?
makes it more difficult for potassium to flow out of the cell which would would cause an immediate reduction in the amount of potassium leaking out of a cell?
An 82-year-old woman is brought to the emergency room complaining of nausea, vomiting, muscle cramps, and generalized weakness. Laboratory analysis reveals significant hyperkalemia. Elevations of extracellular potassium ion concentration will have which of the following effects on nerve membranes?
The potassium conductance will increase
A 22-year-old woman decides to lose weight on a diet suggested by an anorexic friend. She loses about 30 pounds in 45 days, but her serum potassium falls to a level of 2.1 mEq/L (normal: 3.5-5.0 mmol/L). Which of the following changes is most likely to occur in this young woman?
“more negative” = hyperpolarized
The net driving force for an ion is the difference between the membrane potential of the cell and the equilibrium potential of the ion.
Hyperpolarization of the resting membrane potential
The resting membrane potential is especially sensitive to changes in extracellular potassium concentration because the cell membrane is essentially permeable to potassium. Recall that the resting membrane potential of a cell is closest to the equilibrium potential (Nernst potential) of the ion with the highest membrane conductance (permeability). Also, recall that the equilibrium potential for potassium is negative because the concentration of potassium is higher inside the cell compared with outside the cell (thus potassium ions tend to diffuse out of the cell, and this removal of positive charges from the cell interior leads to a net negative charge inside the cell). When the extracellular concentration of potassium is decreased, the transmembrane potassium ion gradient is increased, which causes the potassium equilibrium potential to become more negative. When the potassium equilibrium potential becomes more negative, the membrane potential becomes more negative, or hyperpolarized.
The net driving force for an ion is the difference between the membrane potential of the cell and the equilibrium potential of the ion. For example, if the membrane potential were -90 mV and the potassium equilibrium potential were -94 mV, the net driving force for potassium ions (choice A) would be 4 mV. Decreasing the extracellular potassium concentration will decrease (hyperpolarize) the membrane potential, but the decrease in membrane potential will not be as great as the decrease in potassium equilibrium potential (since potassium conductance is not infinitely high). Therefore, the net driving force for potassium will increase slightly.
Again, the membrane potential is more negative (hyperpolarized), not less negative (depolarized) (choice B)
Decreasing extracellular potassium concentration would tend to decrease (not increase; choice D) intracellular potassium concentration.
Again, the potassium equilibrium potential becomes more negative (not less negative; choice E) when the extracellular potassium concentration decreases
An investigator is studying the equilibrium potentials of a neuronal cell with a resting membrane potential of -70 mV (VM). The equilibrium potentials are shown below:
ENa+ +65 mV
ECl- -85 mV
ECa2+ +120 mV
EK+ -85 mV
Which of the following changes occur if the ion permeability to sodium across the cell membrane is increased?
The resting membrane potential becomes more positive
glucose brought into kidney cell via
2day active transport - diabetes can happen here - with failure to adequately absorb glucose
Elevations of extracellular potassium ion concentration will have which of the following effects on nerve membranes?
The potassium conductance will increase
In a hospital error, a 60-year-old woman is infused with large volumes of a solution that causes lysis of her red blood cells (RBCs). The solution was most likely
b. 300 mM urea Correct
Lysis of the patient’s red blood cells (RBCs) was caused by entry of water and swelling of the cells to the point of rupture. Water would flow into the RBCs if the extracellular fluid became hypotonic (had a lower osmotic pressure) relative to the intracellular fluid. By definition, isotonic solutions do not cause water to flow into or out of cells because the osmotic pressure is the same on both sides of the cell membrane. Hypertonic solutions would cause shrinkage of the RBCs. 150 mM NaCl and 300 mM mannitol are isotonic. 350 mM mannitol and 150 mM CaCl3 are hypertonic. Because the reflection coefficient of urea is <1.0, 300 mM urea is hypotonic.
Solutions A and B are separated by a membrane that is permeable to urea. Solution A is 10 mM urea, and solution B is 5 mM urea. If the concentration of urea in solution A is doubled, the flux of urea across the membrane will
TRIPLE _ J = –PA (CA – CB). Originally, CA – CB = 10 mM – 5 mM = 5 mM. When the urea concentration was doubled in solution A, the concentration difference became 20 mM – 5 mM = 15 mM, or three times the original difference. Therefore, the flux would also triple. Note that the negative sign preceding the equation is ignored if the lower concentration is subtracted from the higher concentration.
The correct answer is: triple
Transport of D- and L-glucose proceeds at the same rate down an electrochemical gradient by which of the following processes?
??
Only two types of transport occur “downhill”—simple and facilitated diffusion. If there is no stereospecificity for the D- or L-isomer, one can conclude that the transport is not carrier-mediated and, therefore, must be simple diffusion.
Which of the following will double the permeability of a solute in a lipid bilayer?
Select one:
a. Doubling the oil/water partition coefficient of the solute Correct
Increasing oil/water partition coefficient increases solubility in a lipid bilayer and therefore increases permeability. Increasing molecular radius and increased membrane thickness decrease permeability. The concentration difference of the solute has no effect on permeability.
Which of the following would occur as a result of the inhibition of Na+, K+-ATPase?
increase in intracellular Na+
causing an increase in intracellular Ca2+
also inhibits Na+–glucose cotransport.
increase in intracellular Na+ concentration. Increased intracellular Na+ concentration decreases the Na+ gradient across the cell membrane, thereby inhibiting Na+–Ca2+ exchange and causing an increase in intracellular Ca2+ concentration. Increased intracellular Na+ concentration also inhibits Na+–glucose cotransport.
The correct answer is: Increased intracellular Ca2+ concentration
Which of the following transport processes is involved if transport of glucose from the intestinal lumen into a small intestinal cell is inhibited by abolishing the usual Na+ gradient across the cell membrane?
cotransport
Adenosine triphosphate (ATP) is used indirectly for which of the following processes?
Select one:
a. Transport of H+ from parietal cells into the lumen of the stomach
b. Absorption of glucose by intestinal epithelial cells Correct
c. Accumulation of Ca2+ by the sarcoplasmic reticulum (SR)
d. Transport of Na+ from intracellular to extracellular fluid
e. Transport of K+ from extracellular to intracellular fluid
All of the processes listed are examples of primary active transport [and therefore use adenosine triphosphate (ATP) directly], except for absorption of glucose by intestinal epithelial cells, which occurs by secondary active transport (i.e., cotransport). Secondary active transport uses the Na+ gradient as an energy source and, therefore, uses ATP indirectly (to maintain the Na+ gradient).
A 56-year-old woman with severe muscle weakness is hospitalized. The only abnormality in her laboratory values is an elevated serum K+ concentration. The elevated serum K+ causes muscle weakness because
Select one:
a. the K+ equilibrium potential is hyperpolarized
b. Na+ channels are opened by depolarization
c.
the Na+ equilibrium potential is hyperpolarized
d.
K+ channels are opened by depolarization
e. Na+ channels are closed by depolarization
f.
the resting membrane potential is hyperpolarized
g.
K+ channels are closed by depolarization
???? Elevated serum K+ concentration causes depolarization of the K+ equilibrium potential, and therefore depolarization of the resting membrane potential in skeletal muscle. Sustained depolarization closes the inactivation gates on Na+ channels and prevents the occurrence of action potentials in the muscle.
solutions A and B are separated by a membrane permeable to water. Solution A is 3 mmol/L glycerol, and Solution B is 4 mmol/L NaCl. Assume that g NaCl = 1.85.
Which of the following will be correct regarding?
Select one:
a. glycerol will move from A to B until its concentration equalizes in both solutions
b. NaCl will move from B to A until its concentration equalizes in both solutions
c. Water will move from B to A Incorrect
d. water will move from A to B
e. there is no water flow between these two solutions
d. water will move from A to B
water moves across them by osmosis from a solution of lower solute concentration to one of higher solute concentration.
A 23-year-old man is brought to the Emergency Department after collapsing during basketball practice. On admission he is lethargic and appears confused. His coach reports that it was hot in the gym and he was drinking a lot of water during practice. An increase in which of the following is the most likely cause of his symptoms?
Select one:
a. Intracellular tonicity
b. Extracellular volume
c. Intracellular volume Correct
d. Plasma volume
e. Extracellular tonicity
intercellular volume
The NMDA receptor
uses both ligand and voltage gated
memory and pain
Where are NMDA receptors found in the body?
NMDA receptors are neurotransmitter receptors that are located in the post-synaptic membrane of a neuron. They are proteins embedded in the membrane of nerve cells that receive signals across the synapse from a previous nerve cell.
nernst equation calculates?
ion’s equilibrium potential
puffer fish and TETRODOtoxins - block
Neurotoxins tetrodotoxins gets name from puffer fish
block NA+ voltage channels - preventing nerve action potentials
can be fatal - nausea, weakness, dizziness
Tetraethylammonium (TEA)
blocks voltage gated K+ channels, the outward K+ current, and repolarization
neuron vs muscle resting potential? Neuron -70, Muscle -90
in a typical neuron, its value is −70 mV, in a typical skeletal muscle cell, its value is −90 mV
hyperkalemia - depolarizes cell - because more potassium on outside of cell - so less of a concentration gradient -
depolarizes cell, which CLOSES NA+ inactivation gates - no action potential can occur
resting membrane potential = which sodium gate stands open?
Inactivation gate - Channel is “closed but available”
Activation gate only OPENS when ACTIVATED
Hyper vs Hypokalemia
Hyper decreases seize of action potential
Hype - increases
Hyperkalemia – a increase in extracellular potassium depolarizes the cell (RMP is less negative) and decreases the size of action potential
Hypokalemia – a decrease in extracellular potassium hyperpolarizes the cell (RMP is more negative) and increases the size of action potential
Na+:
Hypernatremia
Hypernatremia– no change in RMP and larger action membrane potential
Hyponatremia – no change in RMP and smaller action membrane potential
cable properties of action potential
time constant - = RmCm
indicates how quickly a cell depolarizes in response to inward current or hyperpolarizes in response to outward current
Rm (membrane resistance)
Cm (membrane Capicitance) ability of cell to store charge
The membrane resistance is a function of the number of open ion channels - holes in the pipe - fewer holes - higher resistance -
time constant - to change to 63% of final value
length constant - from site of current injection ?? to where potential has fallen to 63% of its original value
when Rm is high - not good flow - time is increased
when Cm high - time goes UP because first have to discharge the stored energy
Length constant
?? It’s the “when membrane resistance is high” part that I don’t understnad
What happens to the length constant if we decrease the membrane resistance?
The length constant decreases, We can see from the expression that increasing membrane resistance will increase the length constant, because it is in the numerator. It’s a bit like sending water down a pipe with lots of little holes in it. The more holes there are, the less water gets to the end of the pipe.
The length constant will be greatest (current will travel the farthest) when the diameter of the nerve is large, when membrane resistance is high, and when internal resistance is low.
The membrane resistance is a function of the number of open ion channels, and the axial resistance is generally a function of the diameter of the axon. The greater the diameter of the axon, the lower the ri. The length constant is used to describe the rise of potential difference across the membrane.
What increases membrane resistance?
Decrease the number of channels in the membrane, C. Increase permeability of individual channels, … Decreasing the number of channels in the membrane makes the ions flow across the membrane less readily. This means that resistance is increased.
continuous conduction vs Saltatory (myelinated) LEAPS - and also has ability to function like a repeater station
Propagation along an unmyelinated axon
Continuous conduction is slow because there are always voltage-gated Na+channels opening, and more and more Na+is rushing into the cell.
When myelination is present, the action potential propagates differently.
When myelination is present, the action potential propagates differently.
- Sodium ions that enter the cell at the initial segment start to spread along the length of the axon segment, but there are no voltage-gated Na+channels until the first node of Ranvier.
- There is not constant opening of Na+ channels along the axon segment - the depolarization spreads at an optimal speed.
- The distance between nodes is the optimal distance to keep the membrane still depolarized above threshold at the next node.
- As Na+spreads along the inside of the membrane of the axon segment, the charge starts to dissipate.
If the node were any farther down the axon, that depolarization would have fallen off too much for voltage-gated Na+channels to be activated at the next node of Ranvier.
If the nodes were any closer together, the speed of propagation would be slower.
two mechanisms increasing conductin of nerve
- increase nerve diameter
- myelination - increases membrane resistance, decreases membrane capacitance (ability to store charge)
- Increasing nerve diameter
Internal resistance, Ri , is inversely proportional to the cross sectional area
the larger the fiber, the lower the internal resistance.
The largest nerves have the longest length constants - current spreads farthest from the active region to propagate action potentials - Myelination
Myelin increases membrane resistance and decreases membrane capacitance
Increased membrane resistance forces current to flow along the path of least resistance of the axon interior
decreased membrane capacitance produces a decrease in time constant
MS Disease - myelination
The most common demyelinating disease of the central nervous system
Autoimmune inflammation and demyelination of CNS (brain and spinal cord) with subsequent axonal damage.
decreases membrane resistance - current LEAKS OUT - not enough action potential when it gets to next node of Ranvier
length constant decreases
clinical presentation of MS - women 20/30s
Acute optic neuritis (painful unilateral visual loss)
diplopia, ataxia, scanning speech, intention tremor, nystagmus
electric shock-like sensation along spine on neck flexion
neurogenic bladder, paraparesis, sensory manifestations affecting the trunk or one or more extremity
Relapsing and remitting is most common clinical course
women in their 20s and 30s
Guillain - Barr - peripheral nervous system (MS central nervous system)
begins in lower extremities -
symmetric ascending muscle weakness/paralysis and depressed/absent DTRs beginning in lower extremities.
Facial paralysis (usually bilateral)
Respiratory failure.
May see autonomic dysregulation (eg, cardiac irregularities, hypertension, hypotension) or sensory abnormalities
Almost all patients survive; majority recover completely after weeks to months.
Difficulty with eye muscles and vision
Difficulty swallowing, speaking, or chewing
Pricking or pins and needles sensations in the hands and feet
Pain that can be severe, particularly at night
Problems with digestion and/or bladder control.
It is the demyelination of Aβ fibers and subsequent conduction block that causes the paralysis.
The exact cause of GBS is not known
Most common subtype is Acute inflammatory demyelinating polyradiculopathy - Autoimmune condition associated with infections that destroys Schwann cells by inflammation and demyelination of peripheral nerves (including cranial nerves III-XII) and motor fibers likely due to molecular mimicry, inoculations, and stress, but no definitive link to pathogens.
Campylobacter jejuni
Viruses – Zika
Guillain Barr - diagnosis, treatment
Diagnosis:
Increased CSF protein with normal cell count (albuminocytologic dissociation).
Treatment:
Respiratory support is critical until recovery.
Plasmapheresis, IV immunoglobulins.
No role for steroids.
May not survive if don’t keep them breathing – remove plasma – replace with other fluids =
membrane potential
outside cell is marked as zero -
The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking
Cations - like Pussycats - are
Positive
Conductance of a channel based upon probability that it is…
open, the higher is its conductance or permeability.
voltage gated sodium gates?
Because the activation gate responds more rapidly to depolarization than the inactivation gate, the Na+ channel first opens and then closes.
This difference in response times of the two gates accounts for the shape and time course of the action potential.
Second messenger gates - are controlled on the inside or the outside?
INSIDE - Second messenger–gated channels have gates that are controlled by changes in levels of intracellular signaling molecules:
cyclic adenosine monophosphate (cAMP)
inositol 1,4,5-triphosphate (IP3).
The gates on Na+ channels in cardiac sinoatrial node are opened by increased intracellular cAMP
ligand gated channels - controlled inside or outside
outside - extracellular
Nicotinic receptors?
on the motor end plate is actually an ion channel that opens when acetylcholine (ACh) binds to it;
when open, it is permeable to Na+ and K+ ions.
What gated channel uses both voltage and ligand?
Ligands? Glutamate and aspartate (at least one is necessary)
Pain and Memory
NMDA receptors are neurotransmitter receptors that are located in the post-synaptic membrane of a neuron. They are proteins embedded in the membrane of nerve cells that receive signals across the synapse from a previous nerve cell.
The NMDA (N-methyl-D-aspartic acid) both voltage- and ligand-gated.
Voltage-gated:
The pore of the NMDA receptor is blocked by Mg2+ if Em is more negative than –70 mV.
This Mg2+ block is removed if Em becomes less negative than –70 mV.
Thus, the NMDA receptor exhibits characteristics of a voltage-gated channel.
Ligand-gated:
Glutamate and aspartate are the endogenous ligands for this receptor.
Binding of one of the ligands is required to open the channel, thus it exhibits characteristics of a ligand-gated channel.
opening of this channel results in depolarization
involved in:
long-term potentiation of cells, thought to be an important component of memory formation
pain transmission
Are sodium or potassium channels larger?
Sodium -
Sodium channels
0.3-0.5 nm in diameter
Inner surface is strongly negatively charged
Potassium channels
Are smaller than Na+ channels (0.3 nm in diameter)
Inner surface is not negatively charged
The hydrated form of K+ is smaller than that of Na+ → K+ ions can easily pass through these channels
Diffusion potential?
A diffusion potential is the potential difference generated across a membrane when a charged solute (an ion) diffuses down its concentration gradient.
Itis caused by diffusion of ions
The concentration gradient is the driving force.
Itcan be generated only if the membrane is permeable to that ion.
The size of the diffusion potential depends on the size of the concentration gradient.
The magnitude of a diffusion potential is measured in millivolts (mV)
The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively charged.
Created by the diffusion of very few ions and, does not result in changes in concentration of the diffusing ions.
The equilibrium potential
is the diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration difference.
At electrochemical equilibrium,
So not only do solutes want to balance out so that they are equally distributed, but charges also want to - and to the extent that a solute with a charge CAN pass thru a membrane - it will - until it balances out -
as it moves though, it changes the electrical charge for both sides
But if there are two solutes, and won’t can’t move - then it’s stuck on its original side, but will experience an electrical change
the chemical and electrical driving forces acting on an ion are equal and opposite, and no further net diffusion occurs
The Nernst equation
is charted for one ion at a time -
EX - Equilibrium potential (mV) for a given ion, X
(𝟐.𝟑𝐑𝐓)/𝐅 - Constant (60 mV at 37C)
z - Charge on the ion (+1 for Na+ , +2 for Ca2+, -1 for Cl-
Ci - Intracellular concentration of X (mmol/L)
Ce - Extracellular concentration of X (mmol/L)
is used to calculate the equilibrium potential for an ion at a given concentration difference across a membrane, assuming that the membrane is permeable to that ion.
Standard equilibrium potentials
E NA+ = +65 mvolts
E CA++ = +120
E K+ = -85
E Cl- = -85
With charge particles - what two forces are at work?
With charged particles, two separate forces must be considered:
- Electrical Force
- Concentration Force
driving force for net diffusion must consider both concentration difference and electrical potential difference across the cell membrane.
The driving force on a given ion is the difference between the actual, measured membrane potential (Em ) and the ion’s calculated equilibrium potential (EX) - difference between the actual Em and the value the ion would “like” the membrane potential to be (its equilibrium potential, as calculated by the Nernst equation)
Net driving force?
mV = Actual membrane force - Equil potental (standard)
When driving force is negative - will a positive or negative ion enter the cell?
positive
And if it is a negative ion inside the cell - it will exit
If Em is equal to the ion’s equilibrium potential
there is no driving force, there will be no net movement of the ion in either direction.
Ionic current occurs when
there is a driving force on the ion AND
the membrane has a conductance to that ion (its ion channels are open)
The direction of ionic current is determined by the direction of the driving force
The magnitude of ionic current is determined by the size of the driving force and the conductance of the ion.
If either the driving force or the conductance of an ion is zero, there can be no net diffusion of that ion across the cell membrane and no current flow.
Resting potential
For example, the resting membrane potential of nerve is −70 mV, which is close to the calculated K+ equilibrium potential of −85 mV, but far from the calculated Na+ equilibrium potential of +65 mV. At rest, the nerve membrane is far more permeable to K+ than to Na+.
The resting membrane potential of most excitable cells falls in the range of
−70 to −80 mV
Itis close to the equilibrium potentials for K+and Cl− (because permeability to these at rest are high)
but far from equilibrium potentials for Na+ and Ca2+
nerve and muscle resting potential? = Em
Em for nerves is ~ - 70 mV while Em for striated muscle is ~ - 90 mV.
Why is K+ - potassium - so much lower than sodium? - leak channels for K+!
Some sodium does leak in however - and that is why need to keep pumping it out
These K+ leak channels may also leak sodium ions slightly but are about 100 times more permeable to potassium than to sodium
potassium diffuses out of the cell at a much faster rate than sodium leaks in.
Excitable tissue has a considerable number of leak channels for K+, but not for Cl–, Na+, or Ca2+. Thus, K+ conductance (g) is high in resting cells.
When the membrane is at rest, K+ ions accumulate inside the cell due to a net movement with the concentration gradient. … Therefore, potassium diffuses out of the cell at a much faster rate than sodium leaks in.
Hyperkalemia - does it depolarize or hyperpolarize?
REMEMBER it is the opposite - HYPOkalemia HYPERpolarizes
Hyperkalemia excites, Hypo decreases excitement - takes them further away from threshold!
Hyperkalemia depolarizes the cell. If acute, excitability of nerves is increased (nerve is closer to threshold for an action potential) and heart arrhythmias may occur.
Hypokalemia hyperpolarizes the cell. This decreases the excitability of nerves (further from threshold) and heart arrhythmias may occur.
if cell is at rest - and sodium is increased - does this depolarize or hyperpolarize the cell?
DEPOLARIZE - moves toward its equilibrium - same as Calcium
Thus decreasing g or changing the extracellular concentration has no effect on Em. - this is not the same for K+
Electrogenic?
This also generates a net flux of water -
This pump is important for volume regulation of excitable tissue.
3 Na+ out, 2 K+ in - the Na+/K+ pump is electrogenic because more positive charges are removed from inside the cell than are replaced. This helps maintain a negative charge inside the cell
Three solutes are pumped out in exchange for 2 solutes. This causes a net flux of water out of the cell. This pump is important for volume regulation of excitable tissue.
how is Resting membrane potential calculated?
RMP (Em) is determined by the permeability (P) and equilibrium potential (Ex) for each of the major permeant ions (Na+, K+, and Cl-):
Resting Membrane Potential of Nerves
A resting neuron has a greater negative charge inside the plasma membrane and a greater positive charge outside
There is more Na+ ions outside a neuron, and more K+ ions inside
This creates a voltage difference across the plasma membrane - the resting membrane potential
Resting membrane potential
. Contribution of the Na+-K+ Pump:
There is continuous pumping of three sodium ions to the outside for each two potassium ions pumped to the inside of the membrane.
The fact that more sodium ions are being pumped to the outside than potassium to the inside causes continual loss of positive charges from inside the membrane;
This creates an additional degree of negativity on the inside beyond that which can be accounted for by diffusion alone.
muscles - more tension when isometric or isotonic contraction?
isometric
The greater the preload, the greater the passive tension in the muscle.
Stretch generates passive tension
how to create the greatest force of contraction?
The greater the number of cross-bridges in contact with the actin filament at any given time, the greater the force of contraction
how to generate active tension?
crossbridge cycling
- the difference between total tension and passive tension
types of tension
Types of tension
Passive: Produced by the preload - the tension developed by stretching the muscle to different lengths.
Active: Produced by cross-bridge cycling - the difference between total tension and passive tension
Total: The sum of active and passive tension - the tension developed when the muscle is stimulated to contract at different lengths
length tension relationship
Length–tension curves are important for understanding both skeletal and cardiac muscle function.
refers to the effect of muscle fiber length on the amount of tension the fiber can develop
The length at which the fiber generates the most active tension is called the optimal length ✭.
The passive length-tension
relationship is thought to occur as a result of the elastic elements within a sarcomere, within a muscle fiber and within the muscle itself.
Muscle behaves like a rubber band.
The elastic properties of the muscle resist this stretch and the resulting tension is recorded.
Point A: No preload - no stretch and no passive tension
Point B: Preload of 1 g stretches muscle, increasing its resting length, resulting in ~1 g of passive tension
Point C: Preload of 5 g increases muscle stretch, producing a greater resting length and thus a greater passive tension.
maximal isometric contraction
the contraction produces tension, but the afterload is much greater than the tension the muscle develops and thus the muscle doesn’t shorten.
afterload?
what the muscles works against - the weight it is lifting
preload - the stretch
ascending limb
when muscle length is decreased, the thin filaments collide with each other reducing the number of possible cross-bridges and reducing active tension.
Ascending limb (between 1.3μm and 2.0μm)– in this section, the force expressed by the sarcomere increases rapidly with increasing sarcomere length (A-B) when muscle length is decreased, the thin filaments collide with each other in the center of the sarcomere, reducing the number of possible cross-bridges and reducing active tension. as contraction proceeds to still shorter sarcomere lengths, the ends of the myosin filaments are crumpled, the strength of contraction approaches zero, but the sarcomere has now contracted to its shortest length.
The active tension is maximal
when there is maximal overlap of thick and thin filaments and maximal possible cross-bridges.
plateau, desceding limb, beyond decending
ascending limb - fiber too short
plateau - optimal length
descending - fiber too long
Plateau (between 2.0μm and 2.2μm)- Lo– in this section, there is no change in force with increasing length as no additional cross-bridges can be formed (B-C)
The active tension is maximal when there is maximal overlap of thick and thin filaments and maximal possible cross-bridges.
Descending limb(between 2.2μm and 3.6μm)–in this section, there is decreasing overlap between actin and myosin filaments, the force that the sarcomere is capable of expressing decreases with increasing length (C-D)
the number of possible cross-bridges is reduced and active tension is reduced
the tension developed by the activated muscle is zero
Beyond descending limb (>3.6μm)– in this section, there is no overlap between actin and myosin filaments. Therefore, no myosin cross-bridges are close enough to the actin active sites in order to bind with them and so no force generation can occur (D)
The increase in the force of contraction of skeletal muscle is regulated by
the number of motor units recruited by the central nervous system (CNS) and by their frequency of activation
The velocity of shortening
The velocity of shortening will be maximal (Vmax) when the afterload on the muscle is zero.
reflects the speed of cross-bridge cycling, determined by the muscle’s ATPase activity.
As the afterload on the muscle increases
think about trying to lift a big weight - can’t move arm as quickly if lifting a heavy weight - if lifting nothing, I can
, the velocity will be decreased because cross-bridges can cycle less rapidly against the higher resistance.
Three times when need ATP
the walk-along mechanism by which the cross-bridges pull the actin filaments
pumping Ca++ from the sarcoplasm into the SR after the contraction is over
pumping Na+ and K+
how is ADP rephosphoroated?
several sources
stored ATP
creatine
anaerobic
aerobic
Phosphocreatine
small reservoir of high-energy phosphate that can readily regenerate ATP from ADP
creatine is formed in the liver from an amino acid Arginine ➝ bloodstream ➝ brain, heart, skeletal muscles ➝ reacts with ATP to form the creatine phosphate
Reaction is catalyzed by creatine phosphokinase (CPK)
excretion of creatinine
In tissues requiring energy spontaneously cyclizes, forming creatinine.
Creatinine is excreted in the urine.
The amount of creatinine excreted each day is constant and depends on body muscle mass.
muscles first use what energy?
The total amount of phosphocreatine in the muscle fiber is about five times as great as the ATP
The combined energy the stored ATP and the phosphocreatine is capable of causing maximal muscle contraction for 5-8 sec
Glycogen anaerobic metabolism
Oxidation of glucose-6-phosphate to pyruvic acid and/or lactic acid liberates energy to convert ADP to ATP
Rapid enzymatic breakdown of the glycogen (by glycogen phosphorylase) to glucose-6-phosphate - glycogenolysis
Glycogen use?
FASTER
No oxygen
Lactate accumulates after 1 minutes
no oxygen required, FASTER than aerobic
Lactate accumulates - glycolysis loses its capability to sustain maximum muscle contraction after about 1 minute
Oxidative metabolism
of glucose, fatty acids, ketones – aerobic process
For the long-term contraction - many hours
slow vs fast
One Slow Red Ox”= type I muscles are slow twitch, red, and use oxidative metabolism
slow
small lots of blood vessels mitochondria need oxygen myoglobin (red) - iron protein w/ oxygen - STORED until needed
low Fibers (Type 1, Red Muscle):
Smaller fibers.
Small mass per motor unit
Lower ATPase activity
More extensive blood vessel system and capillaries to supply extra amounts of oxygen.
Greatly increased numbers of mitochondria, also to support high levels of oxidative metabolism. High capacity for aerobic metabolism, less glycogen
Fibers contain large amounts of myoglobin, an iron-containing protein similar to hemoglobin in red blood cells.
Myoglobin combines with oxygen and stores it until needed; this also greatly speeds oxygen transport to the mitochondria. The myoglobin gives the slow muscle a reddish appearance and the name red muscle
Fast -
larger - greater strength
little oxygen needed
few mitochondria
Extensive sarcoplasmic reticulum for rapid release of calcium ions to initiate contraction.
Large amounts of glycolytic enzymes for rapid release of energy by the glycolytic process, high capacity for anaerobic glycolysis
High ATPase activity
Less extensive blood supply because oxidative metabolism is of secondary importance.
Fewer mitochondria, also because oxidative metabolism is secondary.
A deficit of red myoglobin in fast muscle gives it the name white muscle.
muscle tone
It results entirely from a low rate of nerve impulses coming from the spinal cord
Controlled partly by signals transmitted from the brain to the appropriate spinal cord anterior motoneurons and partly by signals that originate in muscle spindles
muscle fatigue
Increases in almost direct proportion to the rate of depletion of muscle glycogen.
Interruption of blood flow through a contracting muscle leads to almost complete muscle fatigue within 1 or 2 minutes because of the loss of nutrient supply, especially loss of oxygen.
strength training
endurance - increases blood vessels
for delivery of more oxygen and glucose) and mitochondria (for delivery of ATP) in the muscle.
an increase in the number of myofilaments - increases the force - and mass -
muscle hypertrophy
When the total mass of a muscle increases
all muscle hypertrophy results from an increase in the number of actin and myosin filaments in each muscle fiber ➝ enlargement of the individual muscle fibers - fiber hypertrophy.
when the muscle is loaded
Hyperplasia of Muscle Fibers
increasenumber of muscle fibers -fiber hyperplasia
splitting of previously enlarged fibers
adjusting muscle length
type of hypertrophy - stretching can add sarcomeres - especially when younger - several per minutes
when a muscle continually remains shortened
to less than its normal length, sarcomeres at the ends of the muscle fibers can disappear
muscle atrophy
when a muscle loses its nerve supply
when a muscle loses its nerve supply
when a muscle remains unused for many weeks
degradation of the contractile proteins
ATP-dependent ubiquitin-proteasome pathway
muscle in cast?
When a muscle is inactive for an extended period, the rate of synthesis of the contractile proteins in individual muscle fibers decreases, resulting in an overall reduction in muscle mass.
denervation atrophy
, most of the muscle fibers are destroyed and replaced by fibrous and fatty tissue
The fibrous tissue that replaces the muscle fibers during denervation atrophy has a tendency to continue shortening for many months - contracture
poliomyelitis
macromotor units
the remaining nerve fibers branch off to form new axons that then innervate many of the paralyzed muscle fibers - macromotor units, which can contain as many as five times the normal number of muscle fibers for each motoneuron coming from the spinal cord.
Muscular Atrophy
describes a group of diseases which cause a progressive degeneration of the spinal nerves and wasting of the muscles that they control.
Peroneal Muscular Atrophy
Spinal Muscular Atrophy
Muscular Dystrophy
group of diseases which cause progressive weakness in the muscles due to a genetic defect
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
lysosomal proteins are synthesized on RER - others?
Mannose 6 phosphate added in Golgi
Cytosolic, mitochondrial, nuclear, and peroxisomal proteins are all synthesized on free ribosomes
The intended final destination of a new protein is within a peroxisome. However, the peroxisomal targeting signal is not properly incorporated into the precursor protein. The final destination of that protein will therefore be
Peroxisomal proteins are synthesized on free ribosomes and the default pathway is to remain in the cytosol.
mannose 6 phosphate?
A 3-month-old male child has a defect that results in failure to add mannose-6-phosphate to certain proteins within the Golgi complex. This defect will result in abnormal proteins in
Lysosome
tag added to lysosomal proteins in GOLGI
Proteins that function in the Golgi are not modified by the addition of mannose- 6-phosphate. Mitochondrial and nuclear proteins are synthesized on free ribosomes and do not enter the Golgi
Kinases are a class of enzymes that incorporate a phosphate onto their substrates. The catalytic activity of kinases classifies them as members of which of the following enzyme families?
Select one:
a. oxidoreductases
b. transferases Correct
c. ligases
d. isomerases
e. hydrolases
Kinases are any of the various enzymes that catalyze the transfer of a phosphate group from a donor, such as ADP or ATP, to an acceptor. As such,
kinases represent a subfamily of the transferase class of enzyme.
patient was born with a congenital mutation in an enzyme, severely affecting its ability to bind an activation-transfer coenzyme. As a consequence:
d.
The enzyme would be unable to form the transition state complex
e. The enzyme would be unable to bind the substrate of the reaction
transition state complex
A 23-year-old man is seen in the gastroenterologist’s office for a referral concerning a family history of a1-antitrypsin deficiency. The physician arranges for the interventional radiologist to perform a liver biopsy, which will allow a determination of the extent of accumulation of nonsecreted protein in the hepatocyte. Which of the following statements is true concerning proteins like a1-antitrypsin that are normally secreted from the cell?
Select one:
a. The signal sequence is found on the C terminus of the protein
b. Glycosylation takes place only in the endoplasmic reticulum
c. Proteins travel from the endoplasmic reticulum to the Golgi apparatus and are ultimately secreted by exocytosis Correct
d. They contain a hydrophilic signal sequence
e. They are synthesized on ribosomes attached to the smooth endoplasmic reticulum
Alpha-1 antitrypsin (AAT) is a protein normally found in the lungs and the bloodstream. It helps protect the lungs from the damage caused by inflammation that can lead to emphysema and chronic obstructive pulmonary disease (COPD).
Proteins destined to be secreted from the cell travel to the cell membrane via the endoplasmic reticulum and the Golgi apparatus. Such proteins are synthesized on ribosomes attached to the RER.
The proteins enter the endoplasmic reticulum lumen with the aid of a hydrophobic signal sequence at the N terminus of the protein.
Glycosylation takes place in both the endoplasmic reticulum and the Golgi before sorting and sending the protein to its final destination.
Alpha-1 antitrypsin deficiency (AAT deficiency) is an inherited condition that raises your risk for lung and liver disease. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. The liver makes it. If the AAT proteins aren’t the right shape, they get stuck in the liver cells and can’t reach the lungs
Its main function is to balance the action of neutrophil-protease enzymes in the lungs - eg, neutrophil elastase produced by neutrophils in the presence of inflammation, infection or smoking
nascent protein
Chaperones help
(plural nascent proteins) A protein as it is being formed by a ribosome before it folds into its active shape.
cystic fibrosis goes wrong where?
Abnormal post-translational processing of a transmembrane protein
Is Fibrillin is a glycoprotein?
YES - essential for the formation of elastic fibers found in connective tissue. Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffold for deposition of elastin.
Which of the following is the most common and stable conformation for a polypeptide chain?
alpha helix
The protein you are examining forms an α-helical structure more rapidly in an alcohol medium than it does in water. Which of the following is the best explanation for this difference?
hydrogen in water is competing for the bonds - less competition in alcohol
The quaternary structure of a given protein is defined by which of the following?
structure resulting from the interactions between multiple polypeptide chains
Nucleotide excision repair
pyrimidine dimers
not a bunch of these kinds -
Neurological diseases (such as Alzheimer’s) may also have a deficiency in nucleotide excision repair and Cockayne syndrome.
UV-specific excinuclease nicks the dimer on its 5′ side.
thiamine dimers - xero…
this is NOT a base excision repair
Nucleotide excision repair (NER) is a particularly important excision mechanism that removes DNA damage induced by ultraviolet light (UV). UV DNA damage results in bulky DNA adducts - these adducts are mostly thymine dimers and 6,4-photoproducts.
base excision repair - just base removed
In base excision repair, just the damaged base is removed.
In nucleotide excision repair, as in the mismatch repair, a patch of nucleotides is removed.
Which of the following enzymes can be described as a DNA-dependent RNA polymerase?
When the RNA primer of the previous Okazaki fragment is met, DNA polymerase I replaces III and digests the RNA primer, replacing it with appropriate DNA bases.
primase
Primase is a DNA-dependent RNA polymerase located in the primosome at the replication fork of DNA. Primase initiates DNA synthesis by synthesizing a 10-base RNA primer. The DNA-RNA helix formed binds DNA polymerase III, which synthesizes a DNA frag- ment (the Okazaki fragment) in a 5′ to 3′ direction. When the RNA primer of the previous Okazaki fragment is met, DNA polymerase I replaces III and digests the RNA primer, replacing it with appropriate DNA bases. When the RNA primer is completely removed, DNA ligase synthesizes the last phosphodiester bond, thereby sealing the space. What is left is a new lagging strand extended by the new Okazaki fragment with the 10-base RNA primer at its 5′ end.
Reverse transcriptase
an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription.
no proofreading
is a DNA polymerase that uses RNA as a template found in retroviruses as well as normal eukaryotic cells. Unlike DNA polymerase I and III, which proofread for errors during normal synthesis, reverse transcriptase has no proofreading capabilities. Hence, it has an exceedingly high error rate that contributes to the high rate of mutation in retroviruses like HIV.
Deamination
What is the result of Deamination?
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. … The amino group is removed from the amino acid and converted to ammonia. The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy.
is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney.
Cytosine spontaneously deaminates
base excision repair
Neither thymine nor uracil contains an amino group to deaminate.
adenine - hypoxanthine
guanin - xanthine
to form uracil while in DNA. This error is repaired by the uracil-DNA glycosylase system, which recognizes this abnormal base in DNA and initiates the process of base excision repair to correct the mistake. Neither thymine nor uracil contains an amino group to deaminate. When adenine deaminates, the base hypoxanthine is formed (inosine as part of a nucleoside), and guanine deamination will lead to xanthine production.
HNPCC - mismatch repair
is also a right-sided colon cancer.
Defects in repairing double-strand breaks
in DNA are linked to breast cancer.
Mutations in telomerase
would lead to earlier cell senescence and death due to an inability to maintain the proper length of the chromosomes
Primase
Synthesize RNA primers for DNA polymerase
Prevent the single strands of DNA from reannealing during replication
(Single-stranded binding proteins)
Unwind the DNA helix during replication
(helicase)
Repair nuclear DNA in the event of DNA damage
(DNA polymerase and ligase)
topoisomerase inhibitor amsacrine.
to relieve the supercoiling
Topoisomerases (or DNA topoisomerases) are enzymes that participate in the overwinding or underwinding of DNA.
Break and rejoin the DNA helix during replication
Dividing Gram negative bacteria are isolated from the urine of a 34-year-old female with dysuria. The organisms are noted to incorporate uracil into the DNA molecules during replication. This finding is mediated by which of the following enzymes?
uracil=RNA=primer
The correct answer is: Primase
vs
a. DNA polymerase III Incorrect b. DNA polymerase I c. Ligase d. Gyrase e. Primase f. Helicase
High HIV viral load. He is referred to an infectious disease clinic where they begin him on a nucleoside analog. Certain nucleoside analogs inhibit DNA synthesis because they lack which of the following properties required for normal DNA polymerization?
Other point - just thinking -
DNA methylation typically acts to repress gene transcription.
A 3’-hydroxyl
DNA polymerase requires a free 3’ -hydroxyl group on the deoxyribonucleotide, which acts as a nucleophile to attack the 50-a-phosphate of the incoming nucleotide, which forms the phosphodiester bond. Nucleoside analogs inhibit polymerization because they lack the 30 OH for chain elongation. A 7-methyl G modification and a poly(A) tail are added to eu- karyotic mRNA to stabilize the transcript, and are not found in nucleoside analogs. A consensus sequence is a DNA sequence that is found at the promoter region of genes and functions to bind various factors that regulate the transcription of the gene.
Rifampicin inhibits
tuberculosis, etc
directs DNA replication, whereas bacterial Pol I is involved with DNA repair and lagging strand DNA synthesis. An example of a RNA-dependent DNA polymerase is reverse transcriptase, found in retroviruses. Only certain RNA viruses, such as poliovirus, code for RNA-dependent RNA polymerases.
bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase.
Rifampin is an important agent in a multidrug regimen for tuberculosis and works by inhibiting the b subunit of the bacterial DNA-dependent RNA polymerase (RNA po- lymerase). A DNA-dependent DNA polymerase, such as bacterial Pol III, directs DNA replica- tion, whereas bacterial Pol I is involved with DNA repair and lagging strand DNA synthesis. An example of a RNA-dependent DNA polymerase is reverse transcriptase, found in retroviruses. Only certain RNA viruses, such as poliovirus, code for RNA-dependent RNA polymerases.
Quinolone antibiotics inhibit
UTIs
DNA gyrase, a prokaryotic topoisomerase, and are important drugs in the treatment of urinary tract infections.
premature aging - problem where in DNA synthesis?
Unwinding proteins
Before DNA replication can actually begin, unwinding protein must open segments along the DNA double helix. A defective unwinding protein slows the overall rate of DNA synthesis, but does not alter the size of replicated DNA fragments. Defects in DNA synthesis or transcription may produce a phenotype of accelerated aging, as in Cockayne’s syndrome [
The first drug to be effective against AIDS, including the reduction of maternal-to-child AIDS transmission by 30%, was AIDS drug azidothymidine (AZT). Which of the following describes its mechanism of action?
Select one: a. It inhibits viral protein synthesis b. It inhibits viral reverse transcriptase Correct c. It inhibits RNA synthesis d. It inhibits viral DNA polymerase e. It stimulates DNA provirus production Feedback
AIDS treatment drug azidothymidine (AZT) exerts its effect by inhibiting viral reverse transcriptase. Thus, it prevents replication of the human immunodeficiency virus. Reverse transcriptase is an RNA-directed DNA polymerase. The RNA of retroviruses utilizes reverse transcriptase to synthesize DNA provirus, which in turn synthesizes new viral RNA. AZT inhibits DNA provirus production, but does not directly inhibit synthesis of new viral RNA.
The correct answer is: It inhibits viral reverse transcriptase
Which of the following enzymes can polymerize deoxyribonucleotides into DNA?
Select one:
a. Reverse transcriptase
b. DNA ligase
c. Primase
d. RNA polymerase III Incorrect
e. DNA gyrase
Reverse transcriptase is an RNA-dependent DNA polymerase that can synthesize first a single strand and then a double- stranded DNA from a single-strand RNA template. It was originally found in animal retroviruses.
Primase is a DNA-dependent RNA polymerase enzyme that synthesizes an RNA molecule 10 to 200 nucleotides in length that initiates or “primes” DNA synthesis.
DNA ligase joins DNA fragments and DNA gyrase winds or unwinds DNA. Transfer RNA, 5SRNA, and other small RNAs are synthesized by RNA polymerase III (RNA polymerase I syn- thesizes ribosomal RNA and RNA polymerase II synthesizes messenger RNA).
The correct answer is: Reverse transcriptase
Which aspect of telomeric DNA replication is different from that of other chromosomal regions?
Telomerase is therefore an RNA-dependent
The DNA polymerase contains an RNA molecule that serves as template for DNA synthesis
A special DNA polymerase called telomerase is responsible for replication of the telomeric DNA. Telomerase contains an RNA molecule that guides the synthesis of complementary DNA. Telomerase is therefore an RNA-dependent DNA polymerase in a category with reverse transcriptase.
holoenzume vs apoenzyme?
holoenzyme - active enzyme w/ nonprotein component
apoenzyme - without protein compoment - not active
cofactor
coenzyme (vitamins often)
cofactor -metal ion with enzyme
coenzyme if small organic molecule (vitamin?)
cosubstrates
coenzyme that transiently associates with enzyme - when in altered state - like NAD+ (w niacin)
if permanentaly associated w/ enzyme and returns to orginial form - Porsthetic group FAD (w riboflavin)
rate of reaction w/o enzyme slower
enzymes provide alternative reaction pathway that is faster - with a lower free energy activation
doesn’t change equilibrium of reaction - but accelerates it
lower “free energy of activation” the more molectules have sufficient energy to pass thru the transition stae, and therefore have faster rate of reaction
allosteric enzyme curve?
sigmoidal - not hyperbolic - might see the two on top of each other on graph
The special property of Allosteric enzymes is that it contains an allosteric site on top of its active site which binds the substrate.
temperature and enzymes
speed up a bit as temp goes up - but then decrease over 40
bacteria can work at up to 70
Michaelis constant Km reflect?
large Km - low affinity of enzyme for substrate
enzyme’s affinity for substrate
first order, zero order
first order - when S is much less than Km
zero order - when S is much greater than Km
how do irreversible inhibitors bind to enzymes?
Covalent bonds
reversible inhibitors do not use covalent bonds
suicide inhibitors
a type of irreversible inhibitor
ends up killing itself - binds, forms product, product kills enzyme
competitive inhibitor
Vmax stays same, Km goes up - On lineweaver burk - to the right - closer to zero
on hyperbolic curve - w competitive inhibitor - line will be lower - under line with no inhibitor (Km again moves to right -
examples of competitive inhibitors
statins - inhibit HMG-CoZ - lipitor, pravachol re cholesterol - lowers de novo cholesterol synthesis
non-competitive inhibitors bind where?
not on active site - decrease Vmax - (on lineweaver - see a line HIGHER re negative vmax
no affect on Km
on hyperbolic graph - again line is UNDER no inhibitor - but Km doesn’t move - vmax is lowered
many drugs are enzyme inhibitors
ACE (block enzyme cleaving angiotensin I to form II), Aspirin (inhibits prostaglandin and thromboxane)
can rate of enzyme synthesis be changed? yes, but slow
Yes, often happens during development -
also insulin generated as a result of high glucose can stimulate synthesis of some enzymes -
zymogens?
inactive precursor enzymes - secreted by liver - blood coagulation
higher levels of enzyme in blood?
often signifies disease
some enzymes function mostly in one organ - so if see those enzymes, know that organ has a problem
isoenzymes -
creatine kinase - heart attack
enzymes that catalyze same reaction - may likewise identify which tissue because some are tissue specific
Creatine kinase - different forms -
BB, MM, MB
CK1 - BB brain
CK2 - MM skeletal
CK3 - MB cardiac
heart attack - creatine kinase vs troponin T
timing - under 20 hours creatine
will see both for several days after -
troponin will show up 3 - 10 days later
creatine will not show up after about 72 hours
