exam 2 Flashcards
(193 cards)
1
Q
Guanylyl cyclades use _______ ______ as a secondary messenger
A
cyclic GMP
2
Q
Guanylyl cyclades convert ______ into 3’,5’-cyclic monophosphate (cyclic GMP, cGMP)
A
GTP
3
Q
cGMP ________ cGMP-dependent protein kinase G (PKG)
A
activates
4
Q
PKG _________ serine and threonine residues of downstream target proteins
A
phosphorylates
5
Q
What are the two types of guanylyl cyclases
A
membrane-bound, and soluble
6
Q
what type of guanylyl cyclase is a homodimer and responds to natriuretic peptides
A
membrane-bound
7
Q
what type of guanylyl cyclase is a heme-containing enzyme, responds to intracellular NO concentrations, and present in the heart, blood vessels, leads to smooth muscle contraction
A
soluble
8
Q
an increase in blood volume triggers the atrium to release what
A
atrial natriuretic factor
9
Q
what triggers guanylyl cyclase activity in collecting ducts of kidneys
A
atrial natriuretic factor binding
10
Q
where does ANF bind to ANF-receptors
A
collecting ducts of kidneys and vascular smooth muscle
11
Q
increase in cGMP in collecting triggers what that lowers blood volume
A
renal excretion of Na+ and water
12
Q
what activates muscarinic GPCR endothelial on cells via Gq, stimulating IP3 synthesis and Ca2+ release
A
Ach
13
Q
what activates NOS to produce NO from arginine - activates guanylyl cyclase to produce cyclic GMP
A
Ca2+
14
Q
what triggers the smooth muscle to relax, increasing blood flow through the vessel
A
cGMP
15
Q
how is nitric oxide produced
A
nitric oxide synthase
16
Q
cytosolic (soluble) guanylyl cyclase has what prosthetic group
A
heme
17
Q
nitric oxide is synthesized from arginine via what in nearby cells
A
NO synthase
18
Q
an increase in cGMP stimulates cGMP-dependent kinase which decreases cytosolic Ca2+ and then the heart:
A
decreases force of contractions
19
Q
in vascular smooth muscle~ activation of PKG leads to ________ by phosphorylating
A
vasodilation
20
Q
VDCC (voltage-dependent calcium channels) leads to what
A
a decrease influx of Ca2+
21
Q
phospholamban which modulates SR Ca2+ pump leads to
A
re-uptake of Ca2+ into intracellular stores
22
Q
Ca2+-activated K+ channel–> hyper polarization –> closes L-type Ca2+ channels leads to
A
decrease Ca2+ influx
23
Q
what causes mediated Ca2+ release from intracellular stores
A
inhibiting IP3
24
Q
what is produced via Ca2+ dependent NOS
A
NO
25
nitric oxide synthase (NOS) exists in 3 isoforms
NOS2 (inducible), NOS3 (constitutive), NOS1 (constitutive)
26
what are examples of NOS2
macrophages and other cells
27
what are examples of NOS3
'endothelial', platelets
28
what are examples of NOS1
neuronal forms (CNS, ANS)
29
nitroglycerin (NTG) and nitrovasodilators give long-lasting relief from what
angina
30
NTG causes vasodilation and what
decrease myocardial O2 demand
31
what drug was developed as a vasodilator for CVDs
viagra
32
phosphodiesterase (PDEs) convert cGMP to inactive 5'-GMP terminates what
cGMP effect
33
what is a more selective inhibitor for PDE V isoform found in the penis
sildenafil
34
sildenafil causes what
cGMP levels to remain high in the penis, causing vasodilation
35
penile erection is initiated by what
NO release from neurons and endothelial cells
36
PDE5 inhibitors enhance signaling through what pathway
NO-guanylyl cyclase-cGMP-PKG pathway
37
activation of PKG leads to what
relaxation of cavernosal smooth muscle then engorgement of the corpus cavernous with blood
38
gated ion channels regulate what
transport of ions across cell membranes
39
gated ion channels respond to
changes in the membrane potential and ligand binding to specific receptor sites
40
voltage-gated sodium channels, nicotinic acetylcholine (Ach) receptor, ionotropic glutamate receptor, and gamma aminobutyric acid receptor A: these are all examples of what
roles gated ion channels play in the nervous system
41
passive ion fluxes down cellular electrochemical gradients are regulated by a large family of ____ ______ located in the membrane
ion channels
42
voltage-activated, ligand-activated, store-activated, stretch-activated, and temperature-activated channels are all another way to classify what
ion channels
43
changes in the flux of ions across the plasma membrane are critical regulatory events in what cells
excitable and non-excitable
44
the inside of the cell is typically ________ ________ compared with the outside: Vm ___ to ___mV
negatively charged; -50, -70
45
the membrane potential is largely due to what transport of cations by Na+K+ ATPase: 3 Na+ out 2 K+ in
assymmetric transport
46
flow of ionic species across the membrane depends on what
its concentration gradient and overall electrical potential
47
membranes are electrically polarized (t/f)
true
48
to establish the electrochemical gradients required to maintain a membrane potential all cells express what
ion transporters for Na+, K+, Ca2+, and Cl-
49
excitable tissues such as nerve and muscle to generate and transmit electrical impulses, non-excitable cells to trigger biochemical and secretory events, and all cells to support a variety of secondary symport and anti port processes all use what
the electrochemical gradient established
50
nerve signals within nerves propagate as what
electrical impulses
51
propagation of the impulse involves what
opening of voltage-gated Na+ channels
52
opening of voltage-gated Ca++ channels at the end of the axon triggers the release of what
neurotransmitter- Ach
53
Ach opens what on the receiving cell
the ligand-gated ion channel
54
what channels in the nerve and muscle cells generate action potential (AP) that depolarize the membrane from its resting potential of -70mV to +20mV within milliseconds, composed of 3 subunits, a pore-forming a subunit and 2 regulatory b subunits
voltage-gated Na+ channels
55
what are targets for many drugs and toxins (tetrodotoxin and saxitoxin)
voltage-gated Na+ channels
56
what block the pore, inhibit depolarization and therefore block the sensation of pain
local anesthetics
57
what is composed of large a subunit and 3 regulatory subunits (B, o, y subunits)
voltage-gated Ca2+ channels
58
voltage-gated Ca2+ channels _______ an action potential- AP (as in the pacemaker cells of the heart)
initiate
59
voltage-gated Ca2+ channels modify the _______ and ________ of an AP initiated by fast V-G Na+ channels
shape and duration
60
voltage-gated Ca2+ channels initiate Ca2+ influx that stimulates ________ ______ in the nervous system
neurotransmitter release
61
voltage-gated Ca2+ channels initiate Ca2+ influx controls what in cardiac tissue
heart rate and impulse conduction
62
where are L-type Ca2+ channels located in many cells
plasma membrane
63
what is the main Ca2+ source for contraction in smooth and cardiac muscle
VDCCs
64
what are used to treat hypertension, angina, and cardiac arrhythmias (nifedipine and verapamil)
CCB
65
what ionotropic receptors are involved mainly in fast synaptic transmission
ligand-gated ion channel
66
what is the most common structure of ligand-gated ion channels (transmembrane helices arranged around a central aqueous channel)
heteromeric assemblies of 4 or 5 subunits
67
voltage-gated K+ channels are blocked by what
TEA and 4-AP
68
what K+ channels allow K+ to pass inwards easily than outwards
inwardly rectifying
69
what K+ channels outward rectifying exert depolarizing influence, opposing any tendency to excitation-may mediate action of volatile anesthetics such as isoflurane
two-pore domain
70
what nomenclature refers to presence of first double bond from methyl end
omega
71
(IUPAC) refers to double bond from carboxyl (highest priority/most oxidized) end
delta
72
what are important fatty acid-derived molecules involved in signaling
eicosanoids
73
eicosanoids are derived from C2O fatty acid molecules that are derived from what
dietary plant fatty acids
74
consumption of what (including linoleate (18:2)) is required for proper functioning of the eicosanoid pathway
essential fatty acids
75
_______ cannot make double bonds closer to the end than the Delta-9 position
mammals
76
where do we get linoleate (18:2) from? this installs the 2nd double bond
plants
77
linoleate (18:2) is an essential fatty acid, which means we get it from where
ingesting it
78
desaturation to gamma-linolenate (18:3), elongation to eicosatrienoate (20:3), desaturation to arachidonate (20:4), and performed by mixed function oxidases and fatty acid elongates~ in the human body these are all undergone by what
linoleate
79
linoleate is desaturated, elongated, desaturated to what in the human body
arachidonate (20:4)
80
plant and fish-derived fatty acid supplements provide what effects
cardioprotective and triglyceride lowering
81
corn oil, safflower oil, and sunflower oil provide the omega-6 _______ _____
linoleic acid (18:2)
82
linoleic acid alters what
1-series prostaglandins
83
fish oils provide which omega-3 fatty acids
eicosapentaenoic (C20:5) and docosahexaenoic acids (C22:6)
84
fatty acid supplements alter eicosanoid profiles, which results in reductions of what
myocardial infarction and sudden cardiac arrest
85
what was the first FDA-approved EPA-only omega 3 (2012)
Icosapent ethyl (Vascepa)
86
DHA (22:6) has been shown to increase what
LDL (bad) cholesterol
87
EPA only, has been shown to lower ________ without raising LDL (bad) cholesterol
triglycerides
88
eicosanoids are made from what
arachidonate
89
________ are potent short-range hormones
eicosanoids
90
_________ is produced from the arachidonate that is incorporated into the phospholipids of membranes
eicosanoids
91
in response to stimuli (hormone, etc.) ____________ is activated and attacks the C-2 fatty acid, releasing arachidonate
phospholipase A2
92
what is an omega-6 fatty acid derived from linoleum acid, and comes from the diet, but mostly from phospholipids
arachidonic acid (20:4)
93
what strips arachidonic acid off of phospholipids in the cell membrane
phospholipase A2
94
phospholipase A2 family consists of how many groups
15
95
what phospholipase has high affinity for AA, most is released via this enzyme
cytosolic PLA2 (c-PLA2)
96
what phospholipase is responsible for long-term stimulation or sustained release of AA
Secretory PLA2 (s-PLA2), Ca2+-dependent
97
what phospholipase are most AA released via this enzyme is ligated back to phospholipids
Ca2+-independent PLA2 (I-PLA2)
98
cyclooxyrgenase (COX-1/COX-2) give the ______ _____
cyclic prostanoids
99
lipoxygenase results in what
leukotrienes and lipoxins
100
eicosanoid profiles differ based on cell, induction and what?
fatty acid substrate
101
PGH2 synthase is a cyclooxygenase/peroxidase enzyme that functions where
the smooth ER
102
what is step 1 in the conversion of arachidonate to PGs and TXs
PGH2's cyclooxyrgenase activity adds 2 O2 to form PGG2
103
what is step 2 in the conversion of arachidonate to PGs and TXs
PGH2's peroxidase activity converts peroxide to alcohol, creates PGH2
104
_______ inhibit cyclooxyrgenase (COX) activity
NSAIDs
105
what are the two isoforms of PGH2 synthase
COX-1 and COX-2
106
what catalyzes synthesis of prostaglandins that regulate gastric mucin secretion
COX-1
107
what catalyzes synthesis of prostaglandins that mediate pain, inflammation, and fever
COX-2
108
what is an irreversible inhibitor that acetylates a Sea in active site blocking it in both COX isozymes
aspirin (acetylsalicylate)
109
what are competitive inhibitors that resemble substrate; also block active site in both isozymes
ibuprofen and naproxen
110
synthesis of leukotrienes begins with _________
arachidonate
111
in prostaglandin nomenclature the two-letter code signifies which ______ the molecule belongs to
class
112
the subscript "n" in prostaglandin nomenclature means what
the number of double bonds it has
113
what are two examples of prostanoids (cyclooxyrgenase pathway)
PGn (prostaglandins) and TXn (thromboxane)
114
what are two examples of lipoxins and leukotrienes (lipoxygenase pathway)
LTn (leukotriene) and LXn (lipoxins)
115
which series includes omega-6 fatty acids contributing, linoleate (18:2) is eaten and desaturated in our bodies to y-linolenate (18:3), y-linolenate (18:3) is extended in our bodies to eicosatrienoate (20:3), and eicosatrienoate forms this prostanoid and lipoxins
series 1
116
which series is mostly inactive
series 1
117
which series includes membrane-bound eicosatetraenoate/arachidonate (20:4) is hydrolyzed by phospholipase A2, and free arachidonate then goes to form prostanoids and lipoxins
series 2
118
which series have most of the activity in the human body
series 2
119
vasoconstriction, inflammation, pain, induce sleep, blood coagulation, reproduction all occur due to what
series 2
120
omega-3 fatty acids (eicosapentaenoic acid, EPA) lead to formation of _____ __ prostanoids and leukotrienes
series 3
121
which series prostanoids and leukotrienes are weaker than the series 2
series 3
122
cyclooxyrgenase 1 and 2 (COX-1 and COX-2) convert AA into what?
endoperoxides
123
COX-1 and COX-2 are also known as what?
PGH-1 and PGH-2
124
COX-1 and COX-2 are _______
isoforms
125
what is constitutively expressed in most cells and is the isoform responsible for PGs that enable gastric mucus production
COX-1
126
what is inducible, appears to be the more valuable target for NSAIDs medication, and is the isoform responsible for PGs involved in inflammation, pain, and fever
COX-2
127
what is the most selective COX-2 inhibitor that is still available (as of 2012) with monitoring
celecoxib (Celebrex)
128
COX-1 and COX-2 convert AA to what
PGG2 and PGH2
129
COX-1 and COX-2 make what and then hydroxylate it to PGH2
prostaglandin G2 (PGG2)
130
what is the branch point for many prostanoids
PGH2
131
endoperoxides are unstable and are quickly metabolized into other what?
prostacyclins and thromboxanes
132
what results in "housekeeping" prostanoids, such as gastric mucin production
COX-1
133
what results in endothelial vascular prostacyclin PGI2 (important) and normal renal development and function
COX-2
134
PGH2 is cyclized via:
TX/PG synthases and isomerases
135
enzymes are cell-specific and most cells produce how many types or prostanoids
1-2
136
PGs differ based on constituents of what
cyclopentane ring and number of double bonds
137
what undergo different cyclization and isomerizations from the PGs
TXs
138
PGH2 is converted to PGE2 via what
PGE2 synthase
139
How does PGE2 promote vasodilation
by increasing cAMP and decreasing smooth muscle intracellular calcium
140
PGE2 is produced by endothelial cells in the ________
microvasculature
141
dinoprostone is an important PGE2-based relaxant used for what
induce labor
142
what does PGF2a cause
smooth muscle contraction
143
latanoprost is an ophthalmic formulation used to do what
decrease intraocular pressure and decrease ocular hypertension
144
what is a very powerful vasodilator and inhibitor of platelet aggregation
PGI2
145
PGI2 is synthesized by vascular endothelium and is important in what
renal development
146
synthetic PGI2 epoprostenol is used to treat what
pulmonary hypertension
147
what causes muscle contraction and stimulates smooth muscle mitosis
thromboxane A2 (TXA2)
148
thromboxane A2 primarily causes what
aggregation of platelets and vasoconstriction
149
how are lipoxins formed
via 5-,12- and 15- lipoxygenases (LOX)
150
what is 5-LOX activated by
5-LOX-activating protein (FLAP)
151
5-LOX/FLAP oxygenate AA to what
5(s)-HPETE
152
5'-LOX converts 5(s)-HPETE to what
LTA4
153
LTA4 is then hydrolyzed (LTB4) or conjugated with __________
glutathione (LTC4)
154
degradation of LTC4 leads to what
LTD4, LTE4
155
_______ are important cell signaling mediators
leukotrienes
156
________ are released from leukocytes and mast cells/dendritic cells
leukotrienes
157
leukotrienes mediate in what
anaphylactic shock, asthma, and cardiovascular disease
158
where are LTC4 and LTD4 potent vasoconstrictors
the airways
159
action of these leukotrienes increase what
mucus secretion
160
what is a short-lived epoxide and goes on to form many lipoxins
LTA4
161
what allows for activation of leukocytes leading to binding and crossing of endothelium
LTB4
162
______ is also a chemoattractant for leukocytes
LTB4
163
15-LOX-1 and 5-LOX bind what
omega-3 DHA
164
15-LOX-1 and 5-LOX convert omega-3s into what
resolvins
165
what exhibit anti-inflammatory and lipid resolving effects
resolvins
166
aspirin-triggered lipoxins are formed from what
aspirin-acetylated COX-2
167
AA binds to aspirin-acetylated COX-2, which results in formation of what
15-(R)-HETE and 15-epi-LXA4 or 15-epi-LXB4
168
arachidonic acid can also be converted to ________- or epoxyeicosatrienoic acids
hydroxy
169
EETs are transformed into _____, which are less active
DHETs
170
EETs are stored as what in membranes
phospholipids
171
EETs activate what channels
smooth muscle Ca2+/K+
172
EETS mediate in what
vasodilation and lowered BP
173
eicosanoid molecules have a _____ t1/2
short
174
eicosanoid molecules are short-range signaling molecules, acting on what tissues
autocrine or paracrine
175
where to eicosanoid molecules primarily interact
G-protein coupled receptors
176
activity is primarily determined by receptor type and density on a tissue surface for _______ molecules
eicosanoid
177
the PGI2 (IP), PGF2a (FP), and TXA2 (TP) receptors exist as what in humans
single gene variants
178
how many types of PGE2 receptors are there
4
179
two different versions of what receptors exist
LTB and LTC
180
IP and EP2/EP4 receptors cause what
smooth muscle relaxant effects
181
TXA2 and PGF2a bind to what receptors respectively
TP and FP
182
The TP and FP receptors primarily increase what levels
inositol triphosphate (IP3)
183
what is produced in the endocrine tissues and exert their effects on other tissues (original definition)
hormones
184
hormones can exert effects on ________ cells (paracrine) and on the same cell (autocrine)
adjacent
185
how are hormonal effects achieved
hormone-receptor interactions
186
regulation of energy storage, production, and utilization; the adaptation to new environments or conditions of stress; the facilitation of growth and development; the maturation and function of the reproductive system are all major functions of what
hormones
187
what are extracellular chemical signals
hormones
188
hormones must transmit their signal across the ______ _______ in some fashion
lipid bilayer
189
some hormones undergo facilitated diffusion and bind to what
intracellular receptors (Group I)
190
some hormones bind on the surface and initiate intracellular signal cascades
Group II hormones
191
used to treat patients with elevated serum cholesterol
statins
192
the statins resemble mevalonate and are competitive inhibitors of what
HMG-CoA reductase
193
