Lecture 3 Flashcards
What is the purpose of cholesterol
provide rigidity to cell membrane
precursor to sex hormones
What are the 6 hormones derived from cholesterol
Testosterone
Androstenedione
Estradiol
Progesterone
Cortisol
Aldosterone
What is the precursor to testosterone that was abused by baseball players in the past?
Androstenedione
Why is aldosterone able to interact with cortisol receptors?
Both are made from cholesterol so their structure is very similar, so they can react with each other’s receptors
What is the function of Phosphatidylinositol (PI)
used in smooth muscles to produce inositol triphosphate (IP3), regulates muscle contraction
What is the function of Phosphatidylserine (cytosolic)
immune marker
In a healthy cell, serine portion is inside the cell.
if immune system sees serene on the outside it will destroy the cell
What enzyme functions to flip serines to proper orientation
flippase
What does flippase need to reorient serine?
ATP
if cell is dying and isn’t producing enough ATP the flippase will be unable to flip serines and thus the immune system will sweep in
What do combinations of phosphatidyl compounds help produce?
surfactant
What is sphingomyelin?
fatty compound use for
constructing myelin for the nervous system
What is the function of phosphatidylcholine (PCh)?
body can store choline to later assemble acetylcholine
acetylcholine is super important in cell signaling and signal transduction
What mediates destruction of dying cells by the immune system?
energy deficient flippase that is unable to flip serine
What are the 4 phosphatidyl- compounds
Phosphatidylinositol (PI)
Phosphatidylserine (cytosolic)
Phosphatidylcholine (PCh)
Phosphatidylethanolamine (PE)
What is Arachidonic Acid (AA) a parent compound of?
Prostaglandins
TXA2-thromboxane A2
Leukotrienes
EET &HETE
What enzymes convert arachidonic acid to prostaglandins?
COX1 and COX2
What enzymes convert arachidonic acid to leukotrienes?
lipoxygenase (LO)
What does thromboxane A2 (TXA2) do?
released when blood vessel damaged that signals nearby blood vessels to constrict in effort to reduce bleeding
What is a common drug that inhibits COX1 and COX2?
aspirin
NSAIDs
What effects do prostaglandins have?
pain signal ramping,
causes inflammation
What are differences between COX1 and COX2
COX 1 = wide spread, lots of tissues can produce, used more to create TXA2
COX 2= more inducible, the isoform that gets turned on in response to pain
Does naproxen inhibit COX1 or COX2
COX2
Are COX1 inhibitors or COX2 inhibitors more effective in treating pain?
COX2
What is toxic side effect of COX2 inhibitors?
harmful to kidney and cardiac
inhibits 2ndary effect of COX2 keeps kidney healthy and helps heart heal after ischemia
Why do COX inhibitors lead to increased bleeding?
COX is enzyme in prostaglandin pathway of arachidonic acid that also produces TXA2 that helps stop bleeding.
- COX1 (aspirin) = more bleeding
LTA4, LTC4, LTD4, LTE4 are examples of what?
leukotrienes
What is the function of leukotrienes?
Immune mediated inflammatory response - lung swelling, activates mucous glands
What drug is an example of leukotriene synthesis inhibitor?
Singulair - leukotriene receptor antagonist (allergy med)
Directly inhibits lipoxygenase → decrease leukotriene production
What are the 3 pathways of arachidonic acid?
COX1/2 -> Prostaglandins and TXA2
Lipoxygenase -> leukotrienes
HETE/EET -> acute inflammatory disease processes
What are the two types of cell membrane proteins?
Enzymes and Receptors
(Integral and peripheral)
What are the two types of diffusion?
Simple and Facilitated
What are similarities and difference between simple and facilitated diffusion?
similar - don’t require ATP, movement is dictated by concentration gradient
difference- facilitated goes through channel protein, requires a bond and conformational change;
simple is crossing without a protein (ex. gases)
What is an example of a facilitated diffusion?
GLUT transporter
Besides concentration gradient, what gradient also affects diffusion?
electrochemical gradient
cell is normally (-) charged when inactive, (+) when active
What are are the two types of active transport?
1st and 2nd degree
What is an example of 1st degree active transport?
ATPase pump (Na/K pump)
CA2+ pumps
H+ proton pumps in stomach
What is an example of 2nd degree active transport?
sodium-calcium exchanger (NCX) pump- pumps Ca++ out of the cell, moves Na+ into cell
SGLT - uses Na to move glucose in the cell
What is the ratio of Na and K moved by the ATPase pump?
3 Na+ : 2 K+
What is the difference between primary and 2nd degree active transport?
primary directly uses ATP to pump
2nd degree indirectly utilizes energy used by other pumps
Which direction does the ATPase pump K?
from outside to inside of the cell (against concentration gradient)
Which direction does the ATPase pump Na?
from inside to outside of the cell (against concentration gradient)
What is the normal concentration of Na inside the cell (ICF)?
14
10x less inside the cell
What is the normal concentration of Na outside of the cell (ECF)?
140
10x higher than inside the cell
What is the normal concentration of K+ outside of the cell?
4
30x less than inside the cell
What is the normal concentration of K+ inside of the cell?
120
30x higher inside the cell
What is the ratio of Ca++ and Na+ moved by the NCX pump?
1 Ca++ : 3 Na+
Which direction is Na+ moving with an NCX pump?
from outside to inside of cell (down its concentration gradient)
What type of cells have ATPase pumps?
all excitable cells
i.e. neuron & muscle
Which direction is Ca++ moving with an NCX pump
from inside to outside the cell (against its concentration gradient)
What is the importance of ATPase pumps?
central to all action potentials
What is the single most energy requiring process in the body?
ATPase pumps (60-70% of cellular energy)
What is the function of an SGLT pump?
glucose can couple with Na+ to move glucose into the cell faster when needed. Utilizes Na+ concentration gradient
seen in kidney reabsorbing glucose after filtration
Is the Glut transporter an example of facilitated diffusion or active transport?
facilitated diffusion
does not require energy
when glucose binds to transporter conformational change happens and it moves glucose inside and releases
Where are Glut-1 transporters located?
RBCs - not insulin dependent
Where are Glut-4 transporters located?
In insulin dependent cells (muscle/fat)
What factors determine speed of facilitated diffusion?
[] gradient and # of transporters
Arachidonic acid and HETE/EETE are ____________ while Leukotrienes and Prostaglandins are ___________
hydrophobic; hydrophilic
What kind of diffusion are channel proteins used for?
Simple - no binding/energy
How does water cross the cell membrane?
Simple diffusion and aquaporins
What are ion channels? What kind of transport do they contribute to?
A transmembrane protein channel that allows a specific ion to diffuse across the membrane down its concentration or electrochemical gradient.
Simple diffusion
What are the 3 steps for facilitated diffusion?
1- binding to receptor
2- confirmation change to move across cell membrane
3- release from receptor
(No energy required)
How much of the cholesterol in the body is endogenous vs exogenous?
80% endo, 20% exo
How do statins work to reduce cholesterol?
HMG-CoA reductase inhibitor; reduces the amount of endogenous cholesterol made
What are the stress hormones made from cholesterol?
cortisol and aldosterone
What are the sex hormones made from cholesterol?
Estradiol, progesterone, testosterone, androstenedione
What does surfactant do?
Chemical produced in the lungs to maintain the surface tension of the alveoli and keep them from collapsing
Cholesterol is…
Rigid, flat (planar), and lipid soluble
What is the -OH group on cholesterol for?
Cholesterol inside of cell wall; cell sees -OH group and pulls it out of cell wall if needed
-OH group is polar
Acetyl-CoA
Byproduct of metabolism; chemical precursor used to make many products (including cholesterol, makes ATP from glucose and oxygen)
Where do cortisol and aldosterone come from?
Adrenal glands
Schmidt wouldn’t be surprised if a future drug targets _________ instead of just leukotriene receptor antagonist
Lipoxygenases (LO)
What are the 3 examples of primary active transport?
Na/K ATPase, calcium pumps, proton pumps
What transport mechanism is responsible for the bulk of glucose transport to inside cell?
GLUT transporter
What transport mechanism is responsible for the bulk of calcium transport ICF → ECF?
NCX transporter
In what ways can glucose be transported into the cell?
Facilitated diffusion - GLUT
Secondary active transport - SGLT
