Lecture 3 Flashcards
8/28
What is the cell wall made of?
Phospholipid bilayer
What does a phospholipid consist of?
A head: polar group, phosphate, and glycerol
A tail: Fatty acid chain
Describe the tail of a phospholipid?
Fatty acid chain consisting of carbons and hydrogens; uncharged and hydrophobic; oily; on the inner part of the cell wall
Describe the head of a phospholipid?
A charged compound; hydrophilic; oriented to the outer cell wall
What end of the cholesterol structure will stuck out of the cell wall?
HO-
What 2 terms describe a cholesterol?
Planar (flat) and rigid
What does cholesterol do to food?
Changes the texture to more smooth
What does cholesterol do to blood vessels?
More rigid
Can we remove cholesterol from food? What happens when we do?
Yes.
Food texture becomes gross
What are the main type of metabolites of cholesterol?
Sex hormones!
What is the precursor to cholesterol?
What type of compound is this?
Acetyl-CoA and Acetoacetyl-CoA
HMG synthase
What type of drug would you need to combat high cholesterol? And why?
HMG-CoA reductase inhibitor
-vastatin
It inhibits the precursor to cholesterol therefor it interferes with the pathway
What percentage of cholesterol does our body make vs how much is eaten?
Body - 80%
Eaten (exogenous) - 20%
Can you tackle high cholesterol via diet changes?
Yes and no. Only 20% of cholesterol in our bodies come from foods that we eat. We might see a small decrease but we need drugs to help because our bodies are producing 80% of total body cholesterol.
What are the sex hormone metabolites of cholesterol?
Estradiol
Testosterone
Estrogen
Progesterone
Androstenedione
What are the stress hormone metabolites of cholesterol? And what is special about them?
Cortisol and Aldosterone
They are both produced in the adrenal gland and they have cross reactivity because their structures are so similar
What is the precursor to testosterone?
Androstenedione
What is adrostenedione?
A cholesterol metabolite that is a precursor to testosterone
How is a cholesterol metabolite created?
Enzymatic action manipulates the original structure of cholesterol.
If there is no enzyme then you cannot create the metabolite.
What are the “specialized” phospholipids?
Phosphatidylinositol (PI)
Phosphatidylserine (cytosolic)
Phosphatidylethanolamine (PE)
Phosphatidylcholine (PCh)
(Phosphatidyl- phosphate with an attached compound)
What is Phosphatidylinositol (PI)?
Stores IP3 (Inositol triphosphate) to be used for energy during smooth muscle contractions.
What is Phosphatidylserine (cytosolic)?
acts as an immune marker; attached to cell wall on the inside of the cell. When it goes to the outside of the cell wall the body triggers an immune response.
What helps keep
Phosphatidylserine (cytosolic) inside the cell? Describe it.
Flippase; flippase is an enzyme that is stuck in the cell wall that makes sure phosphatidylserine does not migrate the the outer cell. It requires ATP
What happens when Phosphatidylserine (cytosolic) is present on the outside of the cell and the cell does not have ATP?
Flippase will not be able to flip the Phosphatidylserine back to the inside of the cell. Therefore more Phosphatidylserine will become present on the outer cell wall. The body will trigger an immune response to degrade the cell.
What is phosphatidylcholine (PCh)?
Used to store choline which is use in signal transduction.
What is phosphatidylethanolamine (PE)?
PE helps with the maintenance of the structure and function of surfactant in the lungs.
What is Sphingomyelin?
It is a fatty compound that the body uses to make myelin in the nervous system
What is an arachidonic acid?
A long amino acid with saturated and unsaturated areas that is stuck in the cell wall.
What are the 3 important pathways called that metabolite from arachidonic acid?
Prostaglandin/Thromboxane
Leukotriene
EET/HETE
What are the enzymes used in the Prostaglandin/Thromboxane pathway?
COX1 and COX2
PG =
Prostaglandin
TX =
Thromboxane
What is COX1 and COX2?
Clycooxygenase enzymes
What does COX1 and COX2 produce?
PGG2
PGH2
Where is COX1 found?
Throughout the entire body
Where is COX2 found?
Isoform that is turned on with pain; also keeps kidneys and heart health.
What does prostaglandin affect?
It increases pain signals and pain sensitivity
What does Thromboxane A2 do?
Helps control bleeding by initiating vasospasms
What do COX1/COX2 inhibitors do?
What are some examples.
They will decrease pain signaling and sensitivity ultimately decreasing pain by interfering with the PG/TX pathways by decreasing the production of PG and TX. This will ALSO interfere with the production of TX (Thromboxane; think clotting cascade)
What is an example of a COX2 inhibitor? What SE should you be looking for?
Naproxen
Bleeding in the stomach; bleeding in general. Don’t give to someone with stomach ulcers.
What is an example of a COX1 inhibitor?
Aspirin
The more COX2 specific the drug the ______ the drug is.
Stronger
What is another common drug that interferes with the PG/TX pathway?
NSAIDs; Tylenol
Write out the PG/TX pathway.
Arachidonic acid - COX1/COX2 enzymes - PGG2 - PGG2 + COX1/COX2 - PGH2 - PGH2 + Prostaglandin Synthase = PGE2; PGI2; PGF2(A); TXA2
What is the enzyme used in the Leukotriene pathway?
Lipoxygenase (LO)
What do leukotrienes affect?
Immune-mediated inflammation
Affects lungs and mucous glands
Give an example of a leukotriene antagonist?
Singulair
LT =
leukotriene
What does lipoxygenase do?
Enzyme that helps convert Arachidonic acid to leukotrienes
Describe the Leukotriene pathway?
AA - LO + 5-HPETE - LTA4 = LTC4; LTD4; LTE4
What does the 3rd pathway do?
Uses Cytochrome P450 to produce EET and HETE
What are EET and HETE involved in?
They are large fatty compounds that are largely involved in Acute renal failure.
What are enzymes? Where do they hang out at?
Proteins that catalyze a reaction; usually on or close by a receptor
How many times does a GCRP loop?
7 times
What is simple diffusion?
Getting across the cell wall with no help or through a channel protein. There is no binding and no change in conformation. There is no energy required
How does gas get across the cell wall?
Simple diffusion; gas particles are so small they can usually diffuse across the cell membrane without help
What is a protein channel?
A protein that opens to allow the passage of small charged ions and water; can be specific or non specific. There is no energy required
What is diffusion?
Moving from a higher concentration to a lower concentration
What is facilitated diffusion?
A protein that is used by binding to it and manipulating the orientation (conformational change) and then releasing the compound into or out of the cell
How do most sugars get into the cell?
Facilitated diffusion; by a Glut transporter
What percentage of sugar movement is by Glut transporters?
98%
What does insulin do?
Moves more Glut 4 transporters to the cell wall to facilitate glucose to move into the cell
Glut 4 is an ____________
Insulin dependent transporter
What does Glut 1 deal with?
RBC
How can water get into the cell?
-A specific water channel called AQP (Aqua porin channel)
-Or electrolyte channel proteins
Describe the Na+/K+ ATPase pump
This pump uses 1 ATP and pulls off a phosphate (ADP + Pi) to move 2 K+ inside the cell and 3 Na+ out of the cell; Uses a lot of energy; Almost all other pumps are related to this pump
Primary active transport
Describe the Ca++ pump
Takes Ca+ out of the cell; requires ATP
Primary active transport
What does 1st degree (primary) active transport mean?
The pump directly requires ATP
Describe the proton pump.
Acid producing cells in the stomach are transport H+ out of the cell (keeps stomach acidic)
Primary active transport
Describe the NCX pump
Na+/Ca++ exchange pump.
A pump that removes 1 Ca for 3 Na
Secondary active transport
What is secondary active transport mean?
Harnessing energy from another pump; usually the Na/K ATPase pump
Describe the SGLT pump
A glucose is attached to a Na in order to get the glucose into the cell faster in the kidneys
What is the relationship between energy and the pumps?
If there is no energy (not able to pull a phosphate off adenosine) then the pumps cannot operate.
How does an electrochemical gradient work?
Diffusing across gradient for 2 reasons; to neutralize a positive or negative charge and to equalize concentration
What is required if you are going AGAINST the gradient or needing to go faster?
Energy
What is the relationship between the number of transporters and the rate of diffusion?
The more proteins that you have for movement the faster the compound will be moved.
The higher the concentration….
The faster the diffusion/transport
Inside of a resting cell has what type of charge?
Negative
Inside of an active cell has what type of charge?
Negative or positive
Pumps work _________ a gradient
against
