Exam 2 Flashcards
How do phospholipids influence cell membranes
impact what molecules can pass through
permeable to uncharged, nonpolar, & small polar molecules
How does cholesterol influence cell membranes
membrane packs tightly
allows protein to cluster into functional groups
Diffusion barriers of cholesterol enable what
apical-basolateral cell polarization
How do glycolipids influence cell membranes
maintained on extracellular leaflet
asymmetry
How does phosphatidyl serine influence cell membranes
maintained on intracellular leaflet
asymmetry
What does phosphatidyl serine signal if on he outer leaflet
phagocytosis
What are the two types of transporters
active or passive
Are transporters fast
no, involve a conformation change
What are channels
small holes in membrane
Are channels fast
yes, do not involve a conformation change
Are channels often selective
yes
Do channels require energy or a conformational change
no
What are non-gated ion channels (ex?)
channels that are always open
K+ leak channels
What are voltage-gated ion channels (ex?)
channels that are “gated” electrically
K+ or Na+ voltage-gated channels
Sensors of voltage-gated channels respond to what
changing charge on plasma membrane
What are ligand-gated ion channels (ex?)
channels that are “gated” and require ligands to bind to open
Na+ ligand-gated channels
Describe the chemical gradient
ions concentration difference b/w the inside & outside of the cell
Describe the electrical gradient
electrical difference b/w the inside & outside of the cell
What is the electrochemical gradient
takes into account both the electrical & chemical gradients of ions
What molecules receive a greater pull to enter into the cell (not considering concentration gradient)
positive ions
cell interior is negative
Why is the interior of the cell negative
large, negatively charged organic (protein) molecules are on the inside of the cell & cannot leave
Membrane potential depends on what
K+ leak channels & Na+/K+ pump
What is membrane potential expressed as
voltage
What has to be known in order to calculate membrane potential
permeability of membrane to ions & presence of open channels
What factors determine resting membrane potential inside the cell
negatively charged, Na+ low, & K+ high
At rest, what channels are open and what channels are closed
Na+ closed
K+ leak channels open
Define action potential
depolarization of membrane potential
What are the steps of action potential
1) stimulus triggers NT ligand to open up the ligand-gated Na channel
2) Na+ starts entering cell, increasing pos charge on the inside
3) increase in pos charge on the inside opens up the voltage-gated Na+ channels to open
4) Na+ rushes in, depolarizing cell
5) secondary gated channels blocks Na+ at a certain concentration
6) depolarization triggers K+ gated channels to open
7) K+ rushes in & balances charges until blocked at a certain concentration
8) Na+/K+ pump returns membrane to its resting potential
Describe hyperkalemia
increase in extracellular K+
Does hyperkalemia result in more or less driving force inward
more
due to electrochemical gradient
Would hyperkalemia increase or decrease resting membrane potential
decrease
become less neg/ closer to 0
How does hyperkalemia impact action potential
closer to threshold
more likely to happen
Describe hyponatremia
decrease in extracellular Na+
Does hypernatremia result in more or less driving force inward
less
due to electrochemical gradient
Would hypernatremia increase or decrease resting membrane potential
no effect
Na+ channels are closed at rest
How does hyponatremia impact action potential
makes it smaller
shorter peak
What is a common cause of hyponatremia
water intoxication
How does hyponatremia as a result of water intoxication occur
Na+ ions diluted
water rushes into cell
edema occurs
Where is glycocalyx found
attached to extracellular portion of membrane proteins
What is glycocalyx often called
membrane decor b/c it is on the extracellular surface of cells
What are the compositions of glycocalyx
glycolipds & glycoproteins
Where do glycolipids get their diversity from
AA sequence of protein & monosaccharide combos in the polysaccharide
Glyco means what
polysaccharide
What are the functions of glycocalyx
immune recognition (self vs non-self) protective barrier against bacterial invasion pathogen receptor (viral receptor specificity)
O antigen has what
no additional glycocalyx
B antigen has what
added galactose
A antigen has what
added N-acetylgalactosamine
What does glycocalyx do on the intestinal epithelium
increases surface area of microvilli
decreases # of invading pathogens
What cells in the intestinal epithelium have less glycocalyx
antigen sampling cells
Why do the antigen sampling cells have less glycocalyx
provides access to the luminal contents to sample antigens
Are the antigen sampling cells more or less susceptible to bacterial infection
more
Influenza virus hemagglutinin binds to what on epithelial cells
glycoproteins w/ sialic acids
Different sialic linkages result in different binding & impacts what
where the virus infection is permissible
H1N1 hemagglutinin subtype 1 binds to what
alpha 2-6 linked sialic acids
Where is alpha 2-6 linked sialic acids found
upper respiratory tract
so this is where H1N1 infects
H5N1 hemagglutinin subtype 5 binds to what
alpha 2-3 linked siliac acids
Where is alpha 2-3 siliac acids found
avian intestinal mucosa
in humans, lower respiratory tract
so this is where H5N1 infects
What part of SARS-CoV-2 is heavily glycoxylated
spike protein
The glycan shield of SARS-CoV-2 limits what
potential antibody binding sites
What are the components of ECM
fibroblasts, ground substance, & collagen
What do fibroblasts do
make collagen & ground substance
What is found in ground substance
proteins
What does collagen provide
tensile strength
What are glycosaminoglycans
GAGs
large, highly neg charged polysaccharides
What are GAGs called when attached to a protein core
proteoglycans
What GAG is not attached to a protein core
hyaluronic acid
What is the function of hyaluronic acid
pulls in H2O
plumps up skin & resists compression
lubricant in joint fluid
GAGs represent < 10% of entire ECM, but they do what
occupy most of the space
How do GAGs provide compressive strength
form hydrated gels
What causes GAGs to swell
neg charge attracts cations
cations pull water in
When do GAGs help with cell migration
during development & repair
In certain tissues, GAGs have what function
filtration
GAGs serve as what for other molecules
binding sites
GAGs act as attachment to what
fibrous elements
Do GAGs or glycoproteins branch
glycoproteins
Do GAGs or glycoproteins have repeating units
glycoproteins
Why do GAGs fill the ECM
bend, but cannot fold tightly as a hydrogel
Is collagen the same everywhere
no, different types in different tissues
Collagen is synthesized where
in the cell
Is collagen constitutively expressed
yes
What does collagen require to mature
extracellular proteolytic processing
Collagen arrangement defines what
tissue strength properties
Strength based on collagen can be what
in many directions or one direction
Shar pei skin (slimy-ness) is the result of what
overproduction of hyaluronic acid
What direction is skin strong in
many directions
What direction are tendons strong in
one direction
AA sequence of the glycoprotein can be different how
diverse attachment site of protein sequence
Monosacharide combinations in the polysaccharide portion of glycoprotein can be different how
permutations in monosaccharide order
branch points add additional complexity
Besides GAGs and fibers, what is the other component of ECM in CT
non-collagen glycoproteins
Ehlers-Danlos syndrome is a result of what mutation
ADAMTS2 protease
ADAMTS2 protease does what
converts pro-collagen to collagen
Ehler-Danlos syndrome causes a defect in collage synthesis called
Cutis Hyperelastica
How does Cutis Hyperelastica come about
C-terminus of pro-collagen is cut off, but the N-terminus is not removed
What is the functional result of the N-terminus being removed
skin has reduced tensile strength
increased stretch
Elastic fibers are a network of
elastin molecules
Elastic fibers are abundant where
aorta, ligaments, & zonular fibers of the eye
What scaffold helps elastic fibers form myofibrils
fibrillin
What species does Marfan Syndrome occur in
cattle & humans
What caused Marfan Syndrome
mutation in fibrillin
What type of mutation is Marfan Syndrome
autosomal dominant
Marfan Syndrome results in what
dysfunction in elastic fibers
Those w/ Marfan Syndrome are at risk of what
aortic aneurism
What does the first messenger in cellular signaling do
receive extracellular signal
What does the receptor/transducer in cellular signaling do
transmits signals across plasma membrane (protein)
What does the primary effector in cellular signaling do
binds to proteins & regulate their activity
What does the secondary messenger & secondary effector do in cellular signalin
pass along the signal
What are primary & secondary effectors
proteins or enzymes
What are secondary messengers
small molecules
What are the two types of molecular switches
phosphorylation & GTP binding
What does protein kinase do
use ATP to phosphorylate a protein
Do protein kinases (typically) activate or inhibit proteins
activate
What does protein phosphatase do
removes phosphates from proteins
Do protein phosphatases (typically) activate or inhibit proteins
inhibit
How are molecules activated that use GTP binding
GTP replaces the GDP bound to the protein
How are molecules inactivated that use GTP binding
phosphate is removed through GTP hydrolysis
What molecules remove GDP so free GTP can bind (activate)
GEFs
What molecules convert GTP -> GDP (inactivate)
GAPs
Signal ____ on activation and signal _____ before being inactivated
in, out
Transmitter gated membrane receptors is a type of what
cell surface receptor
How are transmitter gated membrane receptors activated
ligand (signal molecule) binds to a receptor
channel opens for ions to flow through
What is an example of a Transmitter gated membrane receptor
acetylcholine receptor at neuromuscular junctions
Different G-protein coupled receptors (GPCRs) can be activated by the same signal but do what
produce different responses depending on the cells
GPCRs are important as what
drug targets
GPCRs activate what
alpha subunit of trimeric G-proteins
How do GPCRs activate the alpha subunit of trimeric G-proteins
GDP/GTP acivity switch
What are the parts of a trimeric G-protein
alpha, beta, & gamma
What do trimeric G-proteins allow GPCRs to do
become coupled to downstream activities
H1 histamine receptor is a type of what
GPCR
What does the alpha unit of the trimeric G -protein activate, following histamine binding to the H1 histamine receptor
phospholipase C
Phospholipase C cleaves what
PIP2 into IP3 & DAG
IP3 activates what
Ca2+ release from ER
DAG & Ca2+ activate what
protein kinase C
protein kinase C activates what
NF-kbeta
NF-kbeta causes what
inflammation & hives
Receptor Tyrosine Kinase (RTK) is a type of what
enzyme-linked receptor
What binds a signal molecule for RTKs
extracellular domain
What leads to activation of RTKs
dimerization
allows for phosphate binding
What are recruited to activated RTKs to pass the signal along
relays
What generatd many binding sites on the RTK for signaling proteins
trans-autophosphorylation after dimerization
Ras has what type of activity switch
GDP/GTP
A mitogen signal for cell division activates what
RTK
What activates Ras GEF
adaptor protein bound to RTK
What does Ras GEF do
removes GDP from Ras protein
Activated Ras initiates what sequence of events
Mitogen-activated protein kinase (MAPK) cascade
Each step of MAPKKK -> MAPKK -> MAPK involves what
ATP hydrolysis
After the MAP’s, what happens & what does it lead to
change in protein activity & gene expression
leads to cell division
Where do pattern recognition receptors (PRRs) operate
on cell surface & extracellularly
What do PRRs function as
act as pathogen sensors
PRRs recognize what
Pathogen-associated molecular patterns (PAMPs)
PAMPs consist of what
double-stranded RNA (viruses) or lipolysaccharides (bacteria)
PRRs create a signal to activate what
an innate immune response
What are examples of PRRs
Toll-like receptors (TLRs)
NOD-like receptors (NLRs)
C-type lectin receptors (CLRs)
RIG-I-like recpetors (RLRs)
PAMP binds to a TLR receptor & the adaptor proteins activate
IKK complex
IKK complex does what
phosphorylates IKB
When IKB is phosphorylated, what happens
gets degraded in proteosomes
Active IKB functions to do what
inhibit NF-kbeta
Active NF-kbeta does what & causes what (different answer than hives one)
alters gene expression; innate immune response
Cytokine binding to cytokine receptors causes what
dimerization
Dimerization of cytokine receptors results in
activation of JAK kinase
Phosphorylation of JAK kinase does what
recruits STAT proteins
Phosphorylated STATs do what
dimerize & translocate to nucleus to alter gene expression
What is the source of somatotropin (GH) & how is it transported through the body
anterior pituitary
thus, GH sent through cardiovascular system
What are the target tissues for GH
skeletal muscle, adipose tissue, bone, & liver
MAP kinase cascade causes what type of growth effects
direct & systemic
MAP kinase cascade involves Ras signalling that leads to the transcription & translation of factors that cause what
cell cycle entry -> proliferation
GH signaling w/ MAP kinase cascade involves
Ras signaling & enzyme-linked receptor (RTK)
GH via MAP kinase cascade stimulates what
muscle, chondrocyte (cartilage), & bone growth during childhood
JAK-STAT pathway for GH stimulates what
induction of IGF-1 in liver
Production of IGF-1 in liver promotes what
growth of liver, bone growth, protein synthesis, increased muscle mass, & activation of stored fat
JAK-STAT pathway involves what molecules
growth hormone
GH receptor (dimerizes)
JAK kinases
STAT proteins
Do Great Danes or Chiuahuas have more IGF-1
Great danes
Elevated GH in mice results in
gigantism
GH deficiency in mice results in
dwarfism
GH insensitivity in mice leads to
dwarfism
Over the long run, decreased GH signaling leads to
a longer lifespand
What does bovine somatotropin do
stimulate IGF-1 production -> survival of mammary alveolar cells
Recombinant bovine somatotropin results in what changes in the cow
increased milk production
increased growth
Glycogen breakdown is stimulated in muscle by
adrenaline (epinephrine)
Glycogen breakdown is stimulated in the liver by
glucagon
What makes cAMP
adenylate cyclase (AC)
What breaks cAMP
PDE
What is protein kinase A (PKA)
dimer of dimers
cAMP has what effect on PKA
removes regulatory part
allows catalytic part to be active
Adrenaline & glucagon are signal molecules that first activate what to lead to glycogen breakdown
GPCR
Activation of the alpha subunit of the trimeric protein results in activation of what in glycogen breakdown
adenylate cyclase (AC)
AC causes the conversion of what into cAMP
ATP
cAMP activates PKA, resulting in
glycogen -> glucose 1-phosphate
If GH hormone releasing hormone stimulates a similar cascade to glycogen breakdown, what does PKA activate instead
CREB
Activated/phosphorylated CREB does what
results in gene transcription of GH
What is the source of adrenaline
adrenal medulla
What are the physiological effects of adrenaline
increased heart rate
increased resp rate
pupil dilation
glycogen breakdwon
alpha 1 activates what, leading to what intracellular signaling events
phospholipase C
leads to PIP3 -> IP3 + DAG
Ca2+ release
Ca2+ release as a result of alpha 1 causes what
smooth muscle contraction of GI & peripheral blood vessels
alpha 2 does what, leading to what
represses AC
decreased levels of cAMP
Decreased cAMP as a result of alpha 2 causes what
smooth muscle contraction of GI sphincter
beta does what, leading to what
activates AC
increased levels of cAMP
Increased cAMP as a result of beta causes what
heart muscle contraction (increases heart rate), smooth muscle relaxation, glycogenolysis, & opening of bronchioles
What kind of molecule is caffeine
xanthine alkaloid
What is the source of caffeine
leaves, seeds, & fruits of some plants
What are the physiological effect of caffeine
neurostimulant
increased heart rate
How does caffeine act as a neurostimulant
counteracts inhibitory effect of adenosine
How does caffeine increase heart rate
PDE inhibited
cAMP conc increases
PKA activity increases
What is the source of cholera toxin
vibrio cholerae
What are the physiological effects of cholera toxin
efflux of ions & water into small intestine
What molecules does cholera toxin affect
alpha subunit of GPCR
What effect does cholera toxin have on the alpha subunit of GPCR
permanently activates it
How does cholera toxin permanently activate the alpha subunit of GPCR
catalyzes a covalent modifcation
ADP-ribose from NAD+ locks onto an Arginine side chain
When the alpha subunit is permanently activated by the cholera toxin, what occurs
AC stimulated
levels of cAMP & PKA increase
chloride channels open
What is a drug that represses AC
enkephalin
What are the phases of the cell cycle
G1, S, G2, & M
G0
G1 phase involves
cell growth
copy of organelles
S phase involves
DNA synthesis
chromosome replication
G2 phase involves
cell growth
synthesis of proteins/ organelles
M phase involves
mitosis
chromosomes separated
G0 phase involves
cell cycle arrested
Cyclins do what
activate CdK
Cyclins allow for control during the cell cycle b/c they undergo
synthesis & degradation
What are examples of the different types of cyclins
G1/S cyclin
M cyclin
S cyclin
What does CdK stand for
cyclin-dependent kinase
When are CdKs active
only when their cyclin activator is present
What do CdKs do
phosphorylate other molecules to activate them
Is CdK expression constant
yes
Activity of CdK rises & falls corresponding to
cyclin binding
What is CAK
CdK activating kinase
Cyclins cause CdK to undergo a conformation change, which allows what to happen
CAK phosphorylates CdK (on threonine)
Do cells in G0 have a lot or a little of CAK
little
Wee1 kinase does what
phosphorylates active (phosphorylated) CdK to temporarily inactivate it
What does Wee1 kinase allow to happen
cell to grow during G2
Wee1 mutants are what
small
Cdc25 phosphatase does what
removes the inactivating phosphate to activate CdK
CKI stands for
cyclin dependent kinase inhibitor
Two types of CKI
p21 & p27
CKI (p21 & p27) do what
bind to the cyclin-CdK complex to inactivate it
When are CKIs expressed
during G0 to prevent cell cycle entry
What does E3 ligase SCF do
degrades inhibitor p27
makes cyclin-CdK complex active again
What events does E2F activation lead to
S-phase gene transcription -> G1/S cyclin -> activated S-CdK -> S phase
What does Rb do when active
inactivates E2F
prevents transcription of S-cyclin
Rb arrests cells at what checkpoint
G1/S
What does Ras do after it receives a mitogen signal
indirectly inactivates Rb
What events happen when Rb is inactivated
EF is liberated
cells pass through the G1/S checkpoint
cell division occurs
What events lead to the indirect activation of Rb by Ras
MAP kinase cascade
activation of G1 cyclin transcription
G1 & cyclin-dependent kinase activation
G1-CdK dependent phosphorylation of Rb
What does mdm2 (E3 ligase) do
binds & inactivates p53
What does mdm2 promote
protease degradation of p53
p53 leads to what cellular events
cell cycle arrest, DNA repair, & cell cycle restart
apoptosis
p53 promotes what
cellular & genetic stability
p53 is active at what checkpoint
G2/M
DNA damage leads to the activation of p53 by
phosphorylation
Activated p53 binds to the regulatory region of what
p21 gene
After p53 binding, translated p21 does what
inactivates G1/S-CdK & S-CdK complexes
The inactivation of the G1/S-CdK & S-CdK complexes leads to
cell cycle arrest & DNA repair
What is the G1/S checkpoint
start transition
restriction point
In the G1/S checkpoint, the cell checks on what
cellsize
nutrients
growth factors
DNA damage
After the G1/S checkpoint, what happens
enter S phase or G0
What is the G2/M checkpoint
gap to mitosis transition
In the G2/M checkpoint, the cell checks on what
DNA damage
DNA replication
After the G2/M checkpoint, what can happen
enter M phase
pause to repair damage
undergo apoptosis
What is the M/G1 checkpoint
metaphase-to-anaphase transition
In the M/G1 checkpoint, the cell checks on what
chromosome attachment
Non-functional Rb leads to what
no break before S phase
aggressive cancer
Hyperactive Ras (meaning Ras activates too early) promotes what
activation of MAP-kinase cascade
cells divide inappropriately b/c Rb is inactivated
aggressive cancer
p53 mutations in the DNA binding domain make it unable to promote transcription of p21, so what happens
inability to inactivate G1/S-CdK & S-CdK complexes
cell progresses right into S phase
aggressive cancer
Apoptosis is described as what type of process
controlled developmental process
Apoptosis is considered what type of pathway for cells if they are not provided with what type of factors
default, survival
Apoptosis is initiated by
viruses
organ/ tissue development
DNA damage
Apoptosis promotes what
homeostasis
Does apoptosis involve single cells or clusters
both
Does apoptosis involve cell swelling or shrinkage
shrinkage
Does apoptosis involve controlled or random DNA fragmentation
controlled
Does apoptosis involve intact or broken cell membranes
intact
Does apoptosis release the cytoplasm through pores or bodies
apoptotic bodies
Does apoptosis involve inflammation
no
Caspase have what active site & cleave where
active site cysteine
cleave at aspartic acid
What do adaptor proteins do to caspases
dimerize, activate, & cleave the initiator caspase
The active initator caspase does what
cleaves the executioner caspase to activate it
The active executioner caspase does what
cleaves multiple subunits
The cleavage of multiple subunits leads to what
apoptosis
Each cleavage results in what
conformational change
Cells are removed in a controlled fashion as what happens
caspases amplify their signals
A few activated caspases lead to
cleavage of cytosolic protein
Many activated caspases lead to
clavage of nuclear lamin
Intrinsic pathway of caspase activation is via what type of pathway
mitochondrial
Intrinsic pathway is activated by
intracellular factors (oxidative stress, hypoxia, nutrient deprevation, & DNA damage)
Intrinsic pathway results in what
mitochondrial membrane permeabilization
cytochrome c leakage into the cytoplasm
What binds to cytochrome c in the cytoplasm
adaptor proteins
Adaptor proteins w/ cytochrome c form what
apoptosome
Apoptosome recruit what that forms what
caspases
forms an active initiator caspase
Active iniatiator caspase does what
activates executioner caspases
Executioner caspases lead to
cellular breakdown
apoptosis
What molecule creates pores for cytocrhome c to leak out
Bax
Is Bax pro-apoptotic or anti-apoptotic
pro-apoptotic
What does Bcl2 do
inhibits Bax
Is Bcl2 pro-apoptotic or anti-apoptotic
anti-apoptotic
What does Bad do
sequesters Bcl2
allows Bax to create pores
Is Bad pro-apoptotic or anti-apoptotic
pro-apoptotic
What molecule promotes the aggregation of Bax so that it can create pores
p53
What does the extrinsic pathway for caspase activation involve
damaged cell displayes a death receptor on its surface
What recognizes the death receptor
killer lymphocyte
Cell-cell binding of the killer lymphocyte to the target cell results in
assembly of adaptor proteins into a death-inducing signaling complex
The death-inducing signaling complex leads to what & ultimately what
activates executioner caspases
apoptosis
Cells constantly decide if they will
divide, differentiate, or die
Sculpting organs requires
proliferation, survival, & apoptosis
Inadequate apoptosis in b/w digits leads to
syndactyly
Too little proliferation causes
Microphthalmia - small eye phenotype
Microphthalmia is a result of
genetic, environmental, or infectious
ex: maternal Vit A deficiency
Too much proliferation causes
Protein myostatin Mighty mice Texel sheep Belgian blue cattle Whippets
Protein myostatin is what
differentiation factor
prevents myogenesis
Mighty mice are transgenic mice mutants with
increased muscle mass & fiber number
Belgian blue cattle are often called what and have a mutation in what leading to what
double muscled
mutation in myostatin
more myocytes
Whippets have what after a mutation in myostatin
increased muscle mass
Examples of second messengers
Ras, cAMP, IP3, & DAG
What does GH stimulate in adipose tissue
release of FAs
What does GH stimulate in skeletal muscle
increase nutrient uptake & utilization
What does GH stimulated in bone
bone growth
What does GH stimulate in liver
increased IGF-1
